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Sample records for elicits cyclooxygenase-2-driven prostaglandin

  1. Inflammation-induced anorexia and fever are elicited by distinct prostaglandin dependent mechanisms, whereas conditioned taste aversion is prostaglandin independent.

    PubMed

    Nilsson, Anna; Wilhelms, Daniel Björk; Mirrasekhian, Elahe; Jaarola, Maarit; Blomqvist, Anders; Engblom, David

    2017-03-01

    Systemic inflammation evokes an array of brain-mediated responses including fever, anorexia and taste aversion. Both fever and anorexia are prostaglandin dependent but it has been unclear if the cell-type that synthesizes the critical prostaglandins is the same. Here we show that pharmacological inhibition or genetic deletion of cyclooxygenase (COX)-2, but not of COX-1, attenuates inflammation-induced anorexia. Mice with deletions of COX-2 selectively in brain endothelial cells displayed attenuated fever, as demonstrated previously, but intact anorexia in response to peripherally injected lipopolysaccharide (10μg/kg). Whereas intracerebroventricular injection of a cyclooxygenase inhibitor markedly reduced anorexia, deletion of COX-2 selectively in neural cells, in myeloid cells or in both brain endothelial and neural cells had no effect on LPS-induced anorexia. In addition, COX-2 in myeloid and neural cells was dispensable for the fever response. Inflammation-induced conditioned taste aversion did not involve prostaglandin signaling at all. These findings collectively show that anorexia, fever and taste aversion are triggered by distinct routes of immune-to-brain signaling.

  2. [Prostaglandins].

    PubMed

    1973-01-01

    The mode of action of prostaglandins (PGs) is today well known; PGs behave as tissular hormones, and exercise their action near the place of their biosynthesis. Such action is exercised through the adenosine cyclic 3',5' monophosphate system. They play an extremely important role in endocrine physiology and pathology, but their pharmaceutical action is mostly evident in inducing delivery at term and in inducing abortion. Several ways of administration, vaginal, intraamniotic, and intrauterine, as well as several modes of dosage have been tried to eliminate the side effects of PGs. PG induced abortion is recommended only between the 15th and the 22nd week of pregnancy; before that time the other classical techniques of abortion are better suited. PGs may induce abortion either by direct action on the myometrium, or by luteolytic destruction of the corpus luteum, thus inhibiting progesterone secretion. PGs may also be used for postcoital contraception since they intervene in induction of menstruation; side effects, however, are very important. If it is true, as it has been reported, that PGE1 and PGE2 can inhibit spermatogenesis and sperm transport, they may eventually be used in male contraception. Aspirin has been proven to inhibit PGs liberation.

  3. Prostaglandin-dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice

    PubMed Central

    Fritz, Michael; Klawonn, Anna M.; Nilsson, Anna; Singh, Anand Kumar; Zajdel, Joanna; Björk Wilhelms, Daniel; Lazarus, Michael; Löfberg, Andreas; Jaarola, Maarit; Örtegren Kugelberg, Unn; Billiar, Timothy R.; Hackam, David J.; Sodhi, Chhinder P.; Breyer, Matthew D.; Jakobsson, Johan; Schwaninger, Markus; Schütz, Günther; Rodriguez Parkitna, Jan; Saper, Clifford B.; Blomqvist, Anders; Engblom, David

    2015-01-01

    Systemic inflammation causes malaise and general feelings of discomfort. This fundamental aspect of the sickness response reduces the quality of life for people suffering from chronic inflammatory diseases and is a nuisance during mild infections like common colds or the flu. To investigate how inflammation is perceived as unpleasant and causes negative affect, we used a behavioral test in which mice avoid an environment that they have learned to associate with inflammation-induced discomfort. Using a combination of cell-type–specific gene deletions, pharmacology, and chemogenetics, we found that systemic inflammation triggered aversion through MyD88-dependent activation of the brain endothelium followed by COX1-mediated cerebral prostaglandin E2 (PGE2) synthesis. Further, we showed that inflammation-induced PGE2 targeted EP1 receptors on striatal dopamine D1 receptor–expressing neurons and that this signaling sequence induced aversion through GABA-mediated inhibition of dopaminergic cells. Finally, we demonstrated that inflammation-induced aversion was not an indirect consequence of fever or anorexia but that it constituted an independent inflammatory symptom triggered by a unique molecular mechanism. Collectively, these findings demonstrate that PGE2-mediated modulation of the dopaminergic motivational circuitry is a key mechanism underlying the negative affect induced by inflammation. PMID:26690700

  4. Delta12-Prostaglandin J2 inhibits the ubiquitin hydrolase UCH-L1 and elicits ubiquitin-protein aggregation without proteasome inhibition.

    PubMed

    Li, Zongmin; Melandri, Francesco; Berdo, Ingrid; Jansen, Marlon; Hunter, Lavonne; Wright, Saundrene; Valbrun, Danielle; Figueiredo-Pereira, Maria E

    2004-07-09

    To investigate molecular mechanisms linking inflammation with neurodegeneration, we treated neuronal cultures with prostaglandins (PGs), which are mediators of inflammation. PGA1, D2, J2, and Delta12-PGJ2, but not PGE2, reduced the viability and raised the levels of ubiquitinated proteins in the neuronal cells. PGJ2 and its metabolite, Delta12-PGJ2, were the most potent of the four neurotoxic PGs tested in inducing both effects. To address the mechanism by which these agents lead to the accumulation of ubiquitinated proteins, we tested their effects on neuronal ubiquitin hydrolases UCH-L1 and UCH-L3 as well as on proteasome activity. Notably, Delta12-PGJ2 inhibited the activities of UCH-L1 (K(i) approximately 3.5 microM) and UCH-L3 (K(i) approximately 8.1 microM) without affecting proteasome activity. Intracellular aggregates containing ubiquitinated proteins were detected in Delta12-PGJ2-treated cells, indicating that these aggregates can form independently of proteasome inhibition. In conclusion, impairment of ubiquitin hydrolase activity, such as triggered by Delta12-PGJ2, may be an important contributor to neurodegeneration associated with accumulation of ubiquitinated proteins and inflammation.

  5. The effects of some prostaglandins on respiration in anaesthetized cats

    PubMed Central

    McQueen, D.S.

    1974-01-01

    1 Some prostaglandins have been found to be capable of affecting respiration in anaesthetized cats. 2 Prostaglandins E1, E2, F2α, A1 and A2 all elicited increases in respiratory frequency when administered to cats anaesthetized with either pentobarbitone or α-chloralose. This effect was abolished by bilateral vagotomy. 3 Prostaglandins of the E and A series, but not prostaglandin F2α, elicited increases in tidal volume which were accompanied by falls in systemic blood pressure in cats anaesthetized with pentobarbitone. The changes in blood pressure were also obtained in cats anaesthetized with α-chloralose, but not the tidal volume changes. 4 It is unlikely that the prostaglandins influenced respiration by direct actions on arterial chemoreceptors or baroreceptors. 5 Mechanisms by which the prostaglandins may be acting to affect respiration are discussed. PMID:4447858

  6. Prostaglandins in reproductive physiology*

    PubMed Central

    Craig, Gillian M.

    1975-01-01

    The role of prostaglandins in reproductive physiology is reviewed with particular emphasis on their possible importance in ovulation in humans. A possible interaction between gonadal steroids, biogenic amines and prostaglandins at hypothalamic-pituitary level, in relation to the release of luteinizing hormone releasing factor, and LH, is discussed. Anomalies regarding the role of oestrogens in LH release are noted, and it is suggested that high oestrogen levels may release prostaglandins from the uterus and/or centrally in humans, in connection with the mid-cycle LH surge and ovulation. A hypothetical role for prostaglandins in sexual behaviour and premenstrual changes is discussed. The hypotheses open up new areas for clinical research to establish the role of prostaglandins in human endocrinology. The need for measurement of prostaglandin metabolites in blood and urine is emphasized. PMID:1089972

  7. Prostaglandins and Inflammation

    PubMed Central

    Ricciotti, Emanuela; FitzGerald, Garret A.

    2011-01-01

    Prostaglandins are lipid autacoids derived from arachidonic acid. They both sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. They are generated from arachidonate by the action of cyclooxygenase (COX) isoenzymes and their biosynthesis is blocked by nonsteroidal anti-inflammatory drugs (NSAIDs), including those selective for inhibition of COX-2. Despite the clinical efficacy of NSAIDs, prostaglandins may function in both the promotion and resolution of inflammation. This review summarizes insights into the mechanisms of prostaglandin generation and the roles of individual mediators and their receptors in modulating the inflammatory response. Prostaglandin biology has potential clinical relevance for atherosclerosis, the response to vascular injury and aortic aneurysm. PMID:21508345

  8. The biochemistry of prostaglandins: a primer.

    PubMed

    O'Neill, C

    1994-06-01

    The membranes of cells serve to endow structural integrity, compartmentalize regions of the cell and allow the generation of a stable intracellular milieu. The lipid component of the membrane forms a matrix for structurally and functionally important proteins. It is also increasingly obvious that these lipids form substrates for the synthesis of a range of molecules which have a central role in cellular communication and regulation. The prostaglandins were the first class of such molecules described and to some extent may serve as an archetype for an understanding of the various classes of lipid mediators. The release of arachidonic acid from lipids (phospholipids in particular) is achieved by lipases (phospholipase A2). Arachidonic acid itself may act directly on cells to modify function. For instance, it may modulate ion channel function. However, it is more often a substrate for cyclooxygenase which produces prostaglandin H2, being the precursor for further prostaglandin and thromboxane synthesis, or for lipoxygenase, to produce the precursor for leukotrienes (a related class of mediators). The prostaglandins may act intracellularly, are readily released from cells to act in an autocrine or paracrine fashion, and may enter the blood vessels or lymphatics to exert endocrine effects. Target cells may contain receptors with relative specificity for various members of the prostaglandin family, thus eliciting some specificity of action by the mediators.

  9. Prostaglandin E2-induced inflammation: Relevance of prostaglandin E receptors.

    PubMed

    Kawahara, Kohichi; Hohjoh, Hirofumi; Inazumi, Tomoaki; Tsuchiya, Soken; Sugimoto, Yukihiko

    2015-04-01

    Prostaglandin E2 (PGE2) is one of the most typical lipid mediators produced from arachidonic acid (AA) by cyclooxygenase (COX) as the rate-limiting enzyme, and acts on four kinds of receptor subtypes (EP1-EP4) to elicit its diverse actions including pyrexia, pain sensation, and inflammation. Recently, the molecular mechanisms underlying the PGE2 actions mediated by each EP subtype have been elucidated by studies using mice deficient in each EP subtype as well as several compounds highly selective to each EP subtype, and their findings now enable us to discuss how PGE2 initiates and exacerbates inflammation at the molecular level. Here, we review the recent advances in PGE2 receptor research by focusing on the activation of mast cells via the EP3 receptor and the control of helper T cells via the EP2/4 receptor, which are the molecular mechanisms involved in PGE2-induced inflammation that had been unknown for many years. We also discuss the roles of PGE2 in acute inflammation and inflammatory disorders, and the usefulness of anti-inflammatory therapies that target EP receptors. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance". Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Prostaglandin E3 metabolism and cancer

    PubMed Central

    Yang, Peiying; Jiang, Yan; Fischer, Susan M.

    2015-01-01

    The anticancer activity of n-3 fatty acids, especially those derived from fish, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid) (DHA), has been studied for centuries. While there is a growing body of evidence that EPA and DHA may influence cancer initiation and development through targeting multiple events of tumor development, the underlying mechanisms responsible for these activities are still not fully understood. A number of studies have suggested that the anticancer activities of EPA and DHA are associated with their effects on eicosanoid metabolism by which they inhibit prostaglandin E2 (PGE2) production. In contrast to DHA, EPA can function as a substrate for cyclooxygenases (COXs) to synthesize unique 3-series prostaglandin compounds, especially PGE3. With advance technology in mass spectrometry, there is renewed interest in studying the role of PGE3 in EPA elicited anti-proliferative activity in various cancers, with some promising results. Here, we summarize the regulation of PGE3 synthesis in cancer cells and its role in EPA elicited anticancer activity. The development of PGE3 and its metabolites as potential biomarkers for future clinical evaluation of EPA and fish oil in cancer care is discussed. PMID:24657656

  11. Prostaglandins: pharmacology and clinical application.

    PubMed

    Karim, S M; Hillier, K

    1974-01-01

    Prostaglandin research has been 1 of the most stimulating features of biomedical investigation in the past decade. Interest developed at a time of expanding knowledge of hormonal and neurohormonal behavior and research work received a tremendous impetus in the early 1960s with the elucidation in Sweden of the chemical structures of prostaglandins, followed by the discovery of their biosynthetic pathways. The original findings of large amounts of prostaglandin in the male accessory genital glands and their secretions, and subsequent discovery in the menstrual and amniotic fluids linked these substances with human production. As a result of further investigation, clinical applications of prostaglandins for the induction of labor and termination of early unwanted pregnancies have been developed. Apart from the functions of the prostaglandins in the reproductive area, they have been shown to have a widespread distribution in the body and produce many different pharmacological effects. Prostaglandins are thought to be involved in the regulation of blood pressure and through their vascular effects have therapeutic potential in the treatment of hypertension and peripheral vascular disease. Through their bronchodilator effect, some prostaglandins may become useful in the treatment of asthma.

  12. Prostaglandins, Lysosomes, and Radiation Injury

    DTIC Science & Technology

    1980-01-01

    SCIENTIFIC REPORT Prostaglandins, lysosomes, and radiation injury 7 P. J. Trocha <G. N. Catravas DTI.C A DEFENSE NUCLEAR AGENCY -LL ARMED FORCES...been shown to be altered with tissue injury . Yet no studies have been performed to monitor lysosomal enzyme activi- ties and PG levels simultaneously...nd R. Pi olm. Raven Pra& New Yort- D 980. Prostaglandins, Lysosomes, and Radiation Injury Paul J. Trocha and George N. Catravas Armed Forces

  13. [Value of prostaglandins in andrology].

    PubMed

    Kreysel, C O

    1994-05-20

    In humans, the highest concentration of prostaglandins is found in the seminal fluid, where they are stored. They probably act as hormones by exercising--via receptors--an influence on cell function. Views on the role of prostaglandins in fertility vary. An explanation for this may be the methodological differences discussed. It remains for future research to establish the true functions of this highly versatile class of compounds in the area of fertility.

  14. The influence of prostaglandins on sperm motility.

    PubMed

    Schlegel, W; Rotermund, S; Färber, G; Nieschlag, E

    1981-01-01

    Prostaglandin E2 and F2 alpha were measured in ejaculates from 10 fertile and 55 infertile men. Prostaglandin F2 alpha was negatively correlated with motility (r = 0.77; p less than 0.01) in normal men. In patients with disturbed fertility, prostaglandin F2 alpha was always higher than in the controls, while prostaglandin E2 was elevated only in patients with persisting varicocele and in those with very low sperm counts and severely impaired motility. There was neither de novo synthesis of prostaglandins in spermatozoa nor were binding sites for prostaglandin E2 and F2 alpha detectable. Inactivation of seminal prostaglandins by incubation with prostaglandin 15-hydroxydehydrogenase resulted in a dramatic fall in motility. The results suggest that prostaglandin F2 alpha act on motility, but the action is not mediated by receptors.

  15. Prostaglandins in swine reproduction.

    PubMed

    Kingston, D J

    1982-05-01

    A review is presented of the roles of prostaglandins in swine reproduction. PGE and PGF are both produced in the ovary. PGE is thought to mediate steroidogenic activity of L.H. on the development of the granulosa cells leading to increased progesterone production in the preovulatory phase of the oestrus cycle. PGF2 acts on the theca cells leading to increased oestradiol and oestrus manifestation. The PG blocker indomethacin prevents oocyte rupture, but not maturation. The L.H. surges in the follicular phase stimulate ovarian PG production which initiates oestrus and ovulation. The uterus produces PGF2alpha. Disorders leading to abortion usually result in excess PGF2alpha production at the endometrium leading to luteolysis. With normal gestation circulatory progesterone levels fall during the last two weeks of pregnancy associated with increased circulatory foetal corticoid levels. The foetal corticoids are thought to trigger endometrial PGF2alpha levels leading to luteolysis and parturition. The use of exogenous PGF2alpha for induction of oestrus and abortion, parturition, semen collection and resolution of anoestrus is reviewed.

  16. Tartrazine and the prostaglandin system.

    PubMed

    Gerber, J G; Payne, N A; Oelz, O; Nies, A S; Oates, J A

    1979-04-01

    The effect of tartrazine on prostaglandin production was evaluated in several in vitro systems in order to elucidate the interrelationship between aspirin-sensitive asthma and tartrazine. Unlike the nonsteroidal anti-inflammatory drugs, tartrazine did not inhibit cyclooxygenase activity in sheep seminal vesicles, guinea pig lung microsomes, and human platelets. Tartrazine had no effect on the activation of acyl hydrolase, which is the rate-limiting step in prostaglandin production. The major metabolite of tartrazine, sulfanilic acid, also had no inhibitory effect on the sheep seminal vesicle cyclooxygenase. In view of these findings, if there is a cross-sensitivity between tartrazine and aspirin in aspirin-sensitive asthmatics, it is unlikely to be on the basis of prostaglandin inhibition.

  17. Ludic Elicitation: Using Games for Knowledge Elicitation

    ERIC Educational Resources Information Center

    Cao, Yan

    2014-01-01

    Knowledge elicitation from human beings is important for many fields, such as decision support systems, risk communication, and customer preference studying. Traditional approaches include observations, questionnaires, structured and semi-structured interviews, and group discussions. Many publications have been studying different techniques for a…

  18. Ludic Elicitation: Using Games for Knowledge Elicitation

    ERIC Educational Resources Information Center

    Cao, Yan

    2014-01-01

    Knowledge elicitation from human beings is important for many fields, such as decision support systems, risk communication, and customer preference studying. Traditional approaches include observations, questionnaires, structured and semi-structured interviews, and group discussions. Many publications have been studying different techniques for a…

  19. The role of prostaglandins in human parturition.

    PubMed

    Gibb, W

    1998-06-01

    Parturition is the process of giving birth, and the molecular mechanisms involved are still to be elucidated. Among the various factors involved prostaglandins appear to have an important role. They are synthesized within the human fetal membranes (amnion and chorion) and decidua and act to ripen the cervix, change membrane structure and contract the myometrium. Prostaglandin concentrations increase in amniotic fluid prior to myometrial contractions, and the activity of prostaglandin H synthase (PGHS) increases in the chorion laeve and amnion at labour. This increase is due to increased expression of the PGHS-2 isoenzyme rather than the PGHS-1 isoenzyme. In animal pregnancy, there is also an increase in the expression of the PGHS-2 isoenzyme, and in both human and animal pregnancies this increase appears to occur in the fetal tissues rather than in the maternal tissues. Prostaglandin metabolism also plays an important role in altering prostaglandin output by the human fetal membranes. Prostaglandin dehydrogenase (PGDH) activity decreases in certain cases of preterm labour, and at term it decreases in the area of the chorion laeve covering the cervix. This may allow active prostaglandins produced by the amnion and chorion to access the cervix and myometrium. Recent studies have indicated that glucocorticoids may be important in regulating prostaglandin formation within the human fetal membranes by increasing expression of PGHS-2 in the amnion and decreasing PGDH activity in the chorion. Prostaglandin formation is also important in infection-induced preterm labour and both phospholipase and PGHS-2 activities can be increased by various cytokines. Prostaglandins are important for the onset of both term and preterm parturition and their effects may result from changes in prostaglandin synthesis, prostaglandin metabolism and expression of various prostaglandin receptors.

  20. Role of prostaglandins in hypertension.

    PubMed

    Colina-Chourio, J A; Godoy-Godoy, N; Avila-Hernández, R M

    2000-04-01

    The role of prostaglandins (PGs) in hypertension (HT) is reviewed, emphasising their biochemical characteristics, physiological effects and functions, especially in the cardiovascular area, and the current evidence of their participation in the antihypertensive activity of a balanced mechanism to maintain normal blood pressure. Also, the clinical use of PGs and the future of such autacoids in the treatment of HT and other diseases or conditions is mentioned.

  1. Prostaglandins for preventing postpartum haemorrhage.

    PubMed

    Tunçalp, Özge; Hofmeyr, G Justus; Gülmezoglu, A Metin

    2012-08-15

    Prostaglandins have mainly been used for postpartum haemorrhage (PPH) when other measures fail. Misoprostol, a new and inexpensive prostaglandin E1 analogue, has been suggested as an alternative for routine management of the third stage of labour. To assess the effects of prophylactic prostaglandin use in the third stage of labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (7 January 2011). We updated this search on 25 May 2012 and added the results to the awaiting classification section. Randomised trials comparing a prostaglandin agent with another uterotonic or no prophylactic uterotonic (nothing or placebo) as part of management of the third stage of labour. The primary outcomes were blood loss 1000 mL or more and the use of additional uterotonics. Two review authors independently assessed eligibility and trial quality and extracted data. We included 72 trials (52,678 women). Oral or sublingual misoprostol compared with placebo is effective in reducing severe PPH (oral: seven trials, 6225 women, not totalled due to significant heterogeneity; sublingual: risk ratio (RR) 0.66; 95% confidence interval (CI) 0.45 to 0.98; one trial, 661 women) and blood transfusion (oral: RR 0.31; 95% CI 0.10 to 0.94; four trials, 3519 women).Compared with conventional injectable uterotonics, oral misoprostol was associated with higher risk of severe PPH (RR 1.33; 95% CI 1.16 to 1.52; 17 trials, 29,797 women) and use of additional uterotonics, but with a trend to fewer blood transfusions (RR 0.84; 95% CI 0.66 to 1.06; 15 trials; 28,213 women). Additional uterotonic data were not totalled due to heterogeneity. Misoprostol use is associated with significant increases in shivering and a temperature of 38º Celsius compared with both placebo and other uterotonics. Oral or sublingual misoprostol shows promising results when compared with placebo in reducing blood loss after delivery. The margin of benefit may be affected by whether other components of the

  2. Recovery of Prostaglandins in Human Cutaneous Inflammation*

    PubMed Central

    Greaves, Malcolm W.; Søndergaard, Jørgen; McDonald-Gibson, Wendy

    1971-01-01

    An in-vivo skin perfusion technique has been used to study the pharmacological activity in inflamed skin of patients with allergic contact eczema. Perfusates from 35 out of 45 patients contained a smooth-muscle-contracting agent with prostaglandin-like properties. Solvent partition followed by thinlayer chromatography revealed this activity to be due to a mixture of prostaglandins E and F. This direct evidence supports the view that prostaglandins mediate inflammation in man. PMID:5572386

  3. Prostaglandin release in canine acute haemorrhagic pancreatitis.

    PubMed Central

    Glazer, G; Bennett, A

    1976-01-01

    Acute haemorrhagic pancreatitis was induced in greyhound dogs by a bile salt/trypsin injection into the main pancreatic duct. Prostaglandin-like activity in the pancreatic venous blood, right atrial blood, and arterial blood was measured by bioassay. Activity rose significantly in the pancreatic venous blood of test dogs but not in controls. Chromatographic analysis of the peritoneal exudate from the dogs with pancreatitis showed high levels of prostaglandin E-like material (mean 43 ng/ml prostaglandin E2 equivalents). It seems likely that prostaglandins contribute to the induced pancreatitis. PMID:1269976

  4. Prostaglandin E, pessaries for induction of labour.

    PubMed

    Pearce, J M; Shepherd, J H; Sims, C D

    1979-03-17

    Vaginal pessaries containing 3 mg of prostaglandin E2 were used to induce labour in 200 patients with variable induction features. Prostaglandin-induced labour was augmented where necessary by synthetic oxytocin. There was on failed induction. Only 23% of patients with favourable induction features and 53% of patients with unfavourable features needed oxytocin. There were no adverse fetal or maternal effects. The prostaglandin E2 pessary was as effective in inducing labour as 350 microgram extra-amniotic prostaglandin E2 in tylose in a comparable group of 200 patients in which there were 4 failed inductions.

  5. Eliciting Sound Memories.

    PubMed

    Harris, Anna

    2015-11-01

    Sensory experiences are often considered triggers of memory, most famously a little French cake dipped in lime blossom tea. Sense memory can also be evoked in public history research through techniques of elicitation. In this article I reflect on different social science methods for eliciting sound memories such as the use of sonic prompts, emplaced interviewing, and sound walks. I include examples from my research on medical listening. The article considers the relevance of this work for the conduct of oral histories, arguing that such methods "break the frame," allowing room for collaborative research connections and insights into the otherwise unarticulatable.

  6. Role of seminal prostaglandins in male fertility. I. Relationship of prostaglandin E and 19-OH prostaglandin E with seminal parameters.

    PubMed

    Isidori, A; Conte, D; Laguzzi, G; Giovenco, P; Dondero, F

    1980-01-01

    Prostaglandin (PG) E and 19-OH PGE, now considered to be the most important of the human seminal prostaglandins, were assayed in infertile and normal men. In the 15 volunteers PGE and 19-OH PGE levels were 23-89 microgram/ml, respectively. In the 4 groups of infertile patients in whom either PGE or 19-OH PGE levels were increased or decreased with respect to normal, sperm concentration and motility were significantly reduced. The negative effects of low levels of seminal prostaglandins on sperm concentration and motility might be correlated respectively with decreased adenylcyclase and testicular androgen activity. The negative effects of high levels of prostaglandins on the seminal fluid might be due either to an inhibition in testicular DNA synthesis or to a decreased sensitivity of the receptors to high titers of prostaglandins.

  7. Homologous desensitization to prostaglandins in rabbit ileum

    SciTech Connect

    Musch, M.W.; Field, M.; Miller, R.J.; Stoff, J.S.

    1987-01-01

    Prostaglandins (PG's) increase short-circuit current (I/sub sc/), inhibit NaCl absorption, and stimulate Cl secretion in rabbit ileum. These changes occur with the following PGs; E/sub 3/, E/sub 1/, nitrilo-I/sub 2/ and, to a lesser extent, with A/sub 2/, D/sub 2/, and F/sub 2..cap alpha../. Arachidonic acid (AA) also stimulates secretion. The PG- or AA-stimulated I/sub sc/ does not persist, however, and on prolonged exposure tachyphylaxis develops. Resensitization of the I/sub sc/ response to PGE/sub 2/ is rapid, being essentially complete in 15 min after the PG is removed. Desensitization to AA is not reflected by diminished PG generation. PGE/sub 2/ release from the mucosa after AA addition is constant, although the AA-stimulated I/sub sc/ decreases. I/sub sc/ measurements indicate that PGE/sub 2/ at slightly below its EC/sub 50/ partially desensitizes and a near-maximal concentration completely desensitizes to PGE/sub 2/ but does not, however, inhibit the subsequent change in I/sub sc/ caused by theophylline or vasoactive intestinal peptide (VIP). Adenosine 3',5'-cyclic monophosphate (cAMP) measurements suggest that desensitization applies to cAMP production. PGE/sub 2/ (10/sup -5/ M) increases mucosal cAMP three- to sevenfold, but this elevation is transient; a second challenge dose, which fails to elicit a I/sub sc/ change, also fails to increase mucosal cAMP. Adenylate cyclase measurements from untreated and PGE/sub 2/-treated enterocytes demonstrate a decrease in stimulation by PGE/sub 2/ but not in stimulation by VIP, fluoride, or 5-guanylylimidodiphosphate.

  8. Bioproduction of prostaglandins in a transgenic liverwort, Marchantia polymorpha.

    PubMed

    Takemura, Miho; Kanamoto, Hirosuke; Nagaya, Shingo; Ohyama, Kanji

    2013-10-01

    Prostaglandins are biologically active substances used in a wide range of medical treatments. Prostaglandins have been supplied mainly by chemical synthesis; nevertheless, the high cost of prostaglandin production remains a factor. To lower the cost of prostaglandin production, we attempted to produce prostaglandins using a liverwort, Marchantia polymorpha L., which accumulates arachidonic acid, which is known as a substrate of prostaglandins. Here we report the first bioproduction of prostaglandins in plant species by introducing a cyclooxygenase gene from a red alga, Gracilaria vermiculophylla into the liverwort. The transgenic liverworts accumulated prostaglandin F2α, prostaglandin E2 and prostaglandin D2 which were not detected in the wild-type liverwort. Moreover, we succeeded in drastically increasing the bioproduction of prostaglandins using an in vitro reaction system with the extracts of transgenic liverworts.

  9. Issues in Requirements Elicitation

    DTIC Science & Technology

    1992-09-01

    systems approach: characterized by Checkland’s Soft Systems Methodology (SSM), which is discussed briefly in Appendix A.6; emphasizes the subjectivity of...methodology for requirements elicitation. A.6 Notes on SSM Both the definition of methodology and the philosophy behind soft systems methodology (SSM...1986. [Checkland 89a] Checkland, Peter. Soft Systems Methodology . Rational Analysis for a Problematic World. New York: John Wiley & Sons, 71-100

  10. Prostaglandins in labor--a translational approach.

    PubMed

    Khan, Abdul H; Carson, Ray J; Nelson, Scott M

    2008-05-01

    The mechanisms involved in the initiation of human labor are largely unknown. Understanding the molecular pathways is fundamental in both the development of effective therapeutic strategies and intervention to prevent preterm labor. Prostaglandins are bioactive lipids and members of the eicosanoids family, derived from arachidonic acid, which act in a paracrine or autocrine manner and function via binding to specific G-protein-coupled receptors, activating intracellular signaling and gene transcription. Prostaglandins have a central role in the maintenance of pregnancy and initiation of labor, with the change from uterine quiescence to a contractile state facilitated by differential expression of prostaglandin receptors within the myometrium and fetal membranes. Clinical evidence for the key role of prostaglandins in human parturition is evident from their successful exploitation as exogenous agents for the induction of labor and the role of prostaglandin synthase inhibitors as a preventative therapy for preterm labor. This review aims to focus on prostaglandin synthesis and metabolism and how differential regulation of prostaglandins and their receptors in gestational tissues interact in the initiation of labor.

  11. Enhancement of scleral macromolecular permeability with prostaglandins.

    PubMed Central

    Weinreb, R N

    2001-01-01

    PURPOSE: It is proposed that the sclera is a metabolically active and pharmacologically responsive tissue. These studies were undertaken to determine whether prostaglandin exposure can enhance scleral permeability to high-molecular-weight substances. METHODS: Topical prostaglandin F2 alpha (PGF2 alpha) was administered to monkeys to determine if this altered the amount of scleral matrix metalloproteinases (MMPs). Experiments also were performed to determine whether the prostaglandin F (FP) receptor and gene transcripts are expressed in normal human sclera. Permeability of organ-cultured human sclera following prostaglandin exposure then was studied and the amount of MMP released into the medium measured. Finally, the permeability of human sclera to basic fibroblast growth factor (FGF-2) was determined following prostaglandin exposure. RESULTS: Topical prostaglandin administration that reduced scleral collagen also increased scleral MMP-1, MMP-2, and MMP-3 by 63 +/- 35%, 267 +/- 210%, and 729 +/- 500%, respectively. FP receptor protein was localized in scleral fibroblasts, and FP receptor gene transcript was identified in sclera. Exposure to prostaglandin F2 alpha, 17-phenyltrinor, PGF2 alpha, or latanoprost acid increased scleral permeability by up to 124%, 183%, or 213%, respectively. In these cultures, MMP-1, MMP-2, and MMP-3 were increased by up to 37%, 267%, and 96%, respectively. Finally, transscleral absorption of FGF-2 was increased by up to 126% with scleral exposure to latanoprost. CONCLUSIONS: These studies demonstrate that the sclera is metabolically active and pharmacologically responsive to prostaglandins. Further, they demonstrate the feasibility of cotreatment with prostaglandin to enhance transscleral delivery of peptides, such as growth factors and high-molecular-weight substances, to the posterior segment of the eye. PMID:11797317

  12. Prostaglandins and reproduction in female farm animals.

    PubMed

    Weems, C W; Weems, Y S; Randel, R D

    2006-03-01

    Prostaglandins impact on ovarian, uterine, placental, and pituitary function to regulate reproduction in female livestock. They play important roles in ovulation, luteal function, maternal recognition of pregnancy, implantation, maintenance of gestation, microbial-induced abortion, parturition, postpartum uterine and ovarian infections, and resumption of postpartum ovarian cyclicity. Prostaglandins have both positive and negative effects on reproduction; they are used to synchronize oestrus, terminate pseudopregnancy in mares, induce parturition, and treat retained placenta, luteinized cysts, pyometra, and chronic endometritis. Improved therapeutic uses for prostaglandins will be developed when we understand better their involvement in implantation, maintenance of luteal function, and establishment and maintenance of pregnancy.

  13. The cyclopentenone 15-deoxy-Δ12,14-prostaglandin J2 binds to and activates H-Ras

    PubMed Central

    Oliva, José Luis; Pérez-Sala, Dolores; Castrillo, Antonio; Martínez, Natalia; Cañada, F. Javier; Boscá, Lisardo; Rojas, José M.

    2003-01-01

    The cyclopentenone 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) induces cell proliferation and mitogen-activated protein kinase activation. Here, we describe that these effects are mediated by 15d-PGJ2-elicited H-Ras activation. We demonstrate that this pathway is specific for H-Ras through the formation of a covalent adduct of 15d-PGJ2 with Cys-184 of H-Ras, but not with N-Ras or K-Ras. Mutation of C184 inhibited H-Ras modification and activation by 15d-PGJ2, whereas serum-elicited stimulation was not affected. These results describe a mechanism for the activation of the Ras signaling pathway, which results from the chemical modification of H-Ras by formation of a covalent adduct with cyclopentenone prostaglandins. PMID:12684535

  14. A comparison of intraamniotic prostaglandin and extraamniotic prostaglandin gel for midtrimester termination of pregnancy.

    PubMed

    Smith, D H; Dalrymple, J C

    1983-02-01

    A comparison between midtrimester abortion induced by the intraamniotic injection of prostaglandin F2 alpha and abortion induced by prostaglandin F2 alpha in Tylose gel administered extraamniotically was made in a group of 40 patients. The induction-abortion interval in the extraamniotic group was 12.1 hours which was significantly shorter (P less than 0.001) than the intraamniotic group (27.6 hours). The placenta was expelled completely more often and there were no cervical lacerations using the extraamniotic method whereas 2 patients required repair of cervical lacerations after intraamniotic prostaglandin. Extraamniotic administration of prostaglandin F2 alpha in Tylose gel is recommended as a safe and more effective method for inducing midtrimester abortion than intraamniotic prostaglandin.

  15. Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis.

    PubMed

    Diggle, Christine P; Parry, David A; Logan, Clare V; Laissue, Paul; Rivera, Carolina; Restrepo, Carlos Martín; Fonseca, Dora J; Morgan, Joanne E; Allanore, Yannick; Fontenay, Michaela; Wipff, Julien; Varret, Mathilde; Gibault, Laure; Dalantaeva, Nadezhda; Korbonits, Márta; Zhou, Bowen; Yuan, Gang; Harifi, Ghita; Cefle, Kivanc; Palanduz, Sukru; Akoglu, Hadim; Zwijnenburg, Petra J; Lichtenbelt, Klaske D; Aubry-Rozier, Bérengère; Superti-Furga, Andrea; Dallapiccola, Bruno; Accadia, Maria; Brancati, Francesco; Sheridan, Eamonn G; Taylor, Graham R; Carr, Ian M; Johnson, Colin A; Markham, Alexander F; Bonthron, David T

    2012-08-01

    Pachydermoperiostosis, or primary hypertrophic osteoarthropathy (PHO), is an inherited multisystem disorder, whose features closely mimic the reactive osteoarthropathy that commonly accompanies neoplastic and inflammatory pathologies. We previously described deficiency of the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (HPGD) as a cause of this condition, implicating elevated circulating prostaglandin E(2) (PGE(2)) as causative of PHO, and perhaps also as the principal mediator of secondary HO. However, PHO is genetically heterogeneous. Here, we use whole-exome sequencing to identify recessive mutations of the prostaglandin transporter SLCO2A1, in individuals lacking HPGD mutations. We performed exome sequencing of four probands with severe PHO, followed by conventional mutation analysis of SLCO2A1 in nine others. Biallelic SLCO2A1 mutations were identified in 12 of the 13 families. Affected individuals had elevated urinary PGE(2), but unlike HPGD-deficient patients, also excreted considerable quantities of the PGE(2) metabolite, PGE-M. Clinical differences between the two groups were also identified, notably that SLCO2A1-deficient individuals have a high frequency of severe anemia due to myelofibrosis. These findings reinforce the key role of systemic or local prostaglandin excess as the stimulus to HO. They also suggest that the induction or maintenance of hematopoietic stem cells by prostaglandin may depend upon transporter activity. © 2012 Wiley Periodicals, Inc.

  16. Separation, identification, and estimation of prostaglandins.

    PubMed

    Shaw, J E; Ramwell, P W

    1969-01-01

    The procedures which may be and are being used to provide a basis for the analysis of submicrogram quantitities of prostaglandins are surveyed. Discussion is focused on the following: 1) sources of standards; 2) properties (effect of different pH values, effect of blood, metabolism, solubility); 3) extraction; 4) detection; 5) estimation (ultraviolet, optical rotatory dispersion, densitometry, radioimmunoassay, enzymatic assay, isotopic methods, bioassay); 6) separation of prostaglandins (separation of PGE, PGF, and PGA with PGB compounds, separation of PGA and PGB compounds, and separation of individual prostaglandins); and 6) structural identification. Methods of prostaglandin analysis, with the required sensitivity for application to individual tissue and fluid specimens, are still in the developmental state. Although prostaglandins may be ubiquitous throughout the animal kingdom, no systematic study of their distribution has been made to date. Recent work has shown that PGE1 has a potent effect on the formation of 3',5' cyclic adenosine monophosphate (cyclic AMP) which is widely believed to be an intracellular intermediate in hormone action.

  17. [Prostaglandins in gynecology and obstetrics].

    PubMed

    Klausch, B; Kyank, H

    1972-06-03

    A review of early research (up through 1970) on prostaglandins (PGs) is presented. Their chemical structure and classification based on their ring-structure is detailed as well as various analytic methods of mammalian tissues and body fluids. For clinical use PGE1 and 2, PGF2alpha and PGA1 are the most significant ones because of their properties. PGs have many physiological activities encompassing many organ systems. Their pharmacological actions include: 1) stimulation of nonvascular smooth muscle; 2) peripheral vasodilation (excluding PGFs which cause vasoconstriction); 3) inhibition of lipolysis; 4) inhibition of platelet aggregation; 5) inhibition of gastric peristalsis and gastric juice secretion; 6) bronchodilation; and 7) inhibition of spontaneous CNS activity. The level of PGEs in semen is closely related to the degree of fertility; normally fertile men have 55 mcg PGE/ml and never less than 11 mcg/ml. Current studies are under way on the effect of PGE in artificial insemination of sperm of subfertile men. PGF2alpha and PGE2 stimulate menstruation and uterine contraction; other PGs inhibit uterine contraction. PGs from semen have a role in sperm transport and possibly act on fallopian tube motility aiding sperm capacitation, and ovum retention and transport. Early trials with PGs point to a possible action as an abortifacient, as a once-a-month contraceptive, or a postconception contraceptive agent. PGF2alpha is found in variable concentrations in maternal blood during contraction of the pregnant uterus; levels increase as labor progresses. PGs have been used for labor induction, for induction of abortion and in mole pregnancy. Given as a constant intravenous infusion they produce regular contractions leading to natural expulsion of the fetus and causing very few side effects in the woman with no adverse effects on the fetus. PGs' action compares favorably with that of oxytocin and is preferable for labor induction in certain pregnancy complications. PGE1

  18. Effects of in vivo administration of epidermal growth factor (EGF) on uterine contractility, prostaglandin production and timing of parturition in rats.

    PubMed

    Ribeiro, M L; Farina, M; Aisemberg, J; Franchi, A

    2003-10-01

    Prostaglandins synthesized by cyclooxygenases elicit uterine contractions during labour. Nitric oxide synthases (NOS) produce nitric oxide (NO), which maintains uterine quiescence during pregnancy. Epidermal growth factor (EGF) interacts with prostaglandins and NO in many biological systems. The aim of this work was to study the effect of the in vivo administration of EGF on uterine contractility, prostaglandin production and timing of parturition in rats. EGF was injected into the uterine lumen of pregnant rats on day 20, 21 or 22 of gestation. Intra-uterine administration of 500 ng EGF on day 21 of gestation delayed parturition for 18 h compared with control rats. Administration of EGF was able to: (i) reduce cyclooxygenase expression in the uterus (determined by western blot analysis) and production of prostaglandins by the uterus (evaluated by conversion of [(14)C]arachidonate to labelled prostaglandins); (ii) decrease prostaglandin concentrations in amniotic fluid (radioimmunoassay); (iii) increase NO production (evaluated by conversion of [(14)C]arginine into [(14)C]citrulline); (iv) increase serum progesterone concentrations to more than control concentrations (P<0.05; radioimmunoassay); and (v) reduce the amplitude of the uterine contractions. The overall effect was a delay in the onset of delivery. This in vivo effect raises the question of whether exogenous EGF plays a role in the initiation of parturition.

  19. Prostaglandins and their receptors in insect biology

    USDA-ARS?s Scientific Manuscript database

    We treat the biological significance of prostaglandins (PGs) and their known receptors in insect biology. PGs and related eicosanoids are oxygenated derivatives of arachidonic acid (AA) and two other C20 polyunsaturated fatty acids. PGs are mostly appreciated in the context of biomedicine, but a gr...

  20. Prostaglandin-induced iridial pigmentation in primates.

    PubMed

    Selén, G; Stjernschantz, J; Resul, B

    1997-02-01

    Latanoprost, a new ocular hypotensive prostaglandin F2 alpha analogue prodrug, was found to induce increased pigmentation of monkey irides in chronic toxicity studies. This prompted us to investigate the effect of naturally occurring prostaglandins on the monkey iris to determine whether this pigmentary effect is unique for latanoprost or whether it is a class effect of prostaglandins. PGF2 alpha-isopropyl ester (IE), PGE2-IE and latanoprost were applied topically to cynomolgus monkey eyes for 18-44 weeks. One eye of each animal was treated, while the other served as control. In addition, latanoprost was applied to sympathectomized monkey eyes. PGF2 alpha-IE, PGE2-IE, as well as latanoprost, induced increased pigmentation in the monkey eye. The first signs of this effect were seen after about two months of treatment. Latanoprost also induced increased pigmentation in sympathectomized eyes. It is concluded that both naturally occurring prostaglandins and their synthetic analogues can induce increased iridial pigmentation in cynomolgus monkeys, and that the effect does not require the presence of sympathetic nerves.

  1. Prostaglandin Actions in Established Insect Cell Lines

    USDA-ARS?s Scientific Manuscript database

    Prostaglandins (PGs) are oxygenated metabolites of arachidonic acid (AA) and two other C20 polyunsaturated fatty acids that serve as biochemical signals that mediate a wide range of physiological functions in animal cells. For example, PGs influence protein expression in establish insect cell lines ...

  2. Identification and Characterization of Novel Microsomal Prostaglandin E Synthase-1 Inhibitors for Analgesia.

    PubMed

    Chandrasekhar, Srinivasan; Harvey, Anita K; Yu, Xiao-Peng; Chambers, Mark G; Oskins, Jennifer L; Lin, Chaohua; Seng, Thomas W; Thibodeaux, Stefan J; Norman, Bryan H; Hughes, Norman E; Schiffler, Matthew A; Fisher, Matthew J

    2016-03-01

    Prostaglandin (PG) E2 plays a critical role in eliciting inflammation. Nonsteroidal anti-inflammatory drugs and selective inhibitors of cyclooxygenase, which block PGE2 production, have been used as key agents in treating inflammation and pain associated with arthritis and other conditions. However, these agents have significant side effects such as gastrointestinal bleeding and myocardial infarction, since they also block the production of prostanoids that are critical for other normal physiologic functions. Microsomal prostaglandin E2 synthase-1 is a membrane-bound terminal enzyme in the prostanoid pathway, which acts downstream of cyclooxygenase 2 and is responsible for PGE2 production during inflammation. Thus, inhibition of this enzyme would be expected to block PGE2 production without inhibiting other prostanoids and would provide analgesic efficacy without the side effects. In this report, we describe novel microsomal prostaglandin E2 synthase-1 inhibitors that are potent in blocking PGE2 production and are efficacious in a guinea pig monoiodoacetate model of arthralgia. These molecules may be useful in treating the signs and symptoms associated with arthritis.

  3. Contribution of covalent protein modification to the antiinflammatory effects of cyclopentenone prostaglandins.

    PubMed

    Pérez-Sala, Dolores; Cernuda-Morollón, Eva; Pineda-Molina, Estela; Cañada, F Javier

    2002-11-01

    Cyclopentenone prostaglandins, which are produced during inflammatory processes, may exert a negative feedback on inflammation. These reactive compounds may form covalent adducts with thiol groups in glutathione or in proteins. The transcription factor NF-kappaB is key for the expression of numerous proinflammatory genes. We have observed that treatment of mesangial cells with 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) inhibits the cytokine-elicited DNA binding activity of NF-kappaB, both in intact cells and in isolated nuclear extracts, thus suggesting a direct effect on DNA binding. By using a biotinylated 15d-PGJ(2) derivative, we have observed that 15d-PGJ(2) forms an adduct with the p50 subunit of NF-kappaB, as shown by Western blot and detection with horseradish peroxidase-conjugated streptavidin. In contrast, a p50 construct that bears a mutation in the cysteine residue involved in DNA binding (Cys62Ser) and is not susceptible to inhibition by 15d-PGJ(2) does not incorporate biotinylated 15d-PGJ(2). The labeling of several polypeptides after incubation of cells with biotinylated 15d-PGJ(2) suggests that there may be multiple targets for modification by 15d-PGJ(2). We propose that the covalent modification of NF-kappaB (and potentially other proteins) by 15d-PGJ(2) may contribute to the antiinflammatory effects of this prostaglandin.

  4. Intracervical prostaglandins for induction of labour.

    PubMed

    Boulvain, M; Kelly, A; Irion, O

    2008-01-23

    Prostaglandins have been used for cervical ripening and induction of labour since the 1970s. The goal of the administration of prostaglandins in the process of induction of labour is to achieve cervical ripening before the onset of contractions. One of the routes of administration that was proposed is intracervical. Using this route, prostaglandins are less easy to administer and the need for exposing the cervix may cause discomfort to the woman. To determine the effects of intracervical prostaglandins for third trimester cervical ripening or induction of labour compared with placebo/no treatment and with vaginal prostaglandins (except misoprostol). We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (August 2007) and bibliographies of relevant papers. Clinical trials comparing intracervical 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 (vaginal prostaglandins, except misoprostol). A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. Fifty-six trials (7738 women) are included. INTRACERVICAL PGE2 WITH PLACEBO/NO TREATMENT: 28 TRIALS, 3764 WOMEN: Four studies reported the number of women who did not achieve vaginal delivery within 24 hours, showing a decreased risk with PGE2 (relative risk (RR) 0.61; 95% confidence interval (CI) 0.47 to 0.79). There was a small, and statistically non-significant, reduction of the risk of caesarean section when PGE2 was used (RR 0.88; 95% CI 0.77 to 1.00). The finding was statistically significant in a subgroup of women with intact membranes and unfavourable cervix only (RR 0.82; 95% CI 0.68 to 0.98). The risk of hyperstimulation with fetal heart rate (FHR) changes was not significantly increased (RR 1.21; 95% CI 0.72 to 2.05). However, the risk of

  5. Effects of prostaglandins and prostaglandin synthesis inhibitors on sexual behavior in boars.

    PubMed

    Estienne, Mark J; Harper, Allen F; Beal, Wilfred E; Crawford, Russell J

    2007-07-01

    Experiments were conducted investigating the effects of prostaglandins and prostaglandin synthesis inhibitors on libido in boars. In Experiment 1, two prostaglandin products were compared with regard to expediting the training of boars for semen collection. On each of five consecutive days, boars received i.m. treatment with saline, dinoprost tromethamine or cloprostenol sodium (n=12/group). On each of day 1 (p=0.06), day 2 (p<0.05), and day 3 (p<0.05), but not on day 4 or 5 (p>0.1), the percentage of boars collected after dinoprost tromethamine, but not cloprostenol sodium, was greater than controls. In Experiments 2 and 3, libido in boars that were trained previously for semen collection was assessed after treatment with prostaglandin synthesis inhibitors, testing the hypothesis that endogenous release of prostaglandin is necessary for expression of sexual behaviors. In Experiment 2, boars treated with flunixin meglumine (n=12) had suppressed (p<0.01) levels of 15-ketodihydro-prostaglandin-F(2) (PGFM) in serum but characteristics of libido were similar (p>0.1) to controls (n=12). In Experiment 3, boars were administered indomethacin orally (n=12) or served as untreated controls (n=12). Indomethacin decreased (p<0.01) serum levels of PGFM, increased (p<0.05) the number of false mounts (mounting artificial sow but dismounting before an ejaculate was collected), and tended (p=0.09) to lengthen the interval between entering the collection pen and the start of ejaculation. These results suggest that prostaglandin synthesis and release is necessary for the complete display of normal sexual behaviors in boars.

  6. Prostaglandins and the regulation of parturition in mares.

    PubMed

    Ousey, J C; Fowden, A L

    2012-02-01

    Prostaglandins play an essential role during the perinatal period in the mare. Prostaglandin concentrations are low for the majority of pregnancy due to the regulatory action of progestagens on those enzymes responsible for metabolism of prostaglandins. Towards term, prostaglandin concentrations gradually increase, closely associated with upregulation of the fetal hypothalamo-pituitary-adrenal axis, stimulation of the prostaglandin synthesising enzyme PGHS-2 and changes in the ratio of progestagens and oestrogens. Recent evidence in the mare indicates that proinflammatory cytokines are key mediators of prostaglandin synthesis both at term parturition in healthy mares and at preterm parturition associated with placental infection. Prostaglandin concentrations rise substantially during active labour and decline after birth, associated with delivery of the placenta. During induced labour, prostaglandin concentrations are variable depending on the proximity to spontaneous parturition at term. Once the proinflammatory endocrine cascade is initiated, it is difficult to prevent active labour by administration of drugs that reduce prostaglandin concentrations in peripheral plasma. Further work is needed to establish the inter-relationships between prostaglandin production and other endocrine changes associated with labour at term and preterm in the mare.

  7. Modulation of macrophage activation by prostaglandins

    PubMed Central

    Carnuccio, R.; D'Acquisto, F.; Rosa, M. Di

    1996-01-01

    The effect of prostaglandtn E2, iloprost and cAMP on both nitric oxide and tumour necrosis factor-α release in J774 macrophages has been studied. Both prostaglandin E2 and iloprost inhibited, in a concentration-dependent fashion, the lipopolysaccharide-induced generation of nitric oxide and tumour necrosis factor-α. The inhibitory effect of these prostanoids seems to be mediated by an increase of the second messenger cAMP since it was mimicked by dibutyryl cAMP and potentiated by the selective type IV phosphodiesterase inhibitor RO-20-1724. Our results suggest that the inhibition of nitric oxide release by prostaglandin E2 and iloprost in lipopolysaccharide-activated J774 macrophages may be secondary to the inhibition of tumour necrosis factor-α generation, which in turn is likely to be mediated by cAMP. PMID:18475691

  8. Prostaglandin synthesis inhibition and postprandial intestinal hyperemia.

    PubMed

    Gallavan, R H; Chou, C C

    1982-02-01

    The effect of prostaglandin synthesis inhibition on the postprandial intestinal hyperemia was examined in the jejunum of anesthetized dogs. Both intravenous and intra-arterial infusion of the cyclooxygenase inhibitors indomethacin and mefenamic acid reduced resting jejunal blood flow and markedly enhanced the food-induced jejunal hyperemia. The jejunal vascular response to food did not change after either intravenous or intra-arterial infusion of the carrier solutions or intra-arterial infusion of angiotensin II. The enhancement of the jejunal hyperemia was associated with an increase in the food-induced increase in jejunal oxygen consumption. Infusion of the cyclooxygenase inhibitors increased the mean amplitude of the monophasic intestinal contractions; however, this did not appear to play a role in the enhancement of the food-induced hyperemia. The study indicates that inhibition of prostaglandin synthesis has a marked effect on the postprandial intestinal hyperemia and that this may be due to its enhancement of the jejunal metabolic response to food. The prostaglandins involved and their mechanism of action are unknown.

  9. Animal-like prostaglandins in marine microalgae.

    PubMed

    Di Dato, Valeria; Orefice, Ida; Amato, Alberto; Fontanarosa, Carolina; Amoresano, Angela; Cutignano, Adele; Ianora, Adrianna; Romano, Giovanna

    2017-03-28

    Diatoms are among the most successful primary producers in ocean and freshwater environments. Deriving from a secondary endosymbiotic event, diatoms have a mixed genome containing bacterial, animal and plant genes encoding for metabolic pathways that may account for their evolutionary success. Studying the transcriptomes of two strains of the diatom Skeletonema marinoi, we report, for the first time in microalgae, an active animal-like prostaglandin pathway that is differentially expressed in the two strains. Prostaglandins are hormone-like mediators in many physiological and pathological processes in mammals, playing a pivotal role in inflammatory responses. They are also present in macroalgae and invertebrates, where they act as defense and communication mediators. The occurrence of animal-like prostaglandins in unicellular photosynthetic eukaryotes opens up new intriguing perspectives on the evolution and role of these molecules in the marine environment as possible mediators in cell-to-cell signaling, eventually influencing population dynamics in the plankton.The ISME Journal advance online publication, 28 March 2017; doi:10.1038/ismej.2017.27.

  10. Prostaglandin E2 Regulation of Chondrocyte Proliferation and Differentiation

    DTIC Science & Technology

    1994-05-01

    increases bone prostaglandin E. Effect of acetylsalicylic acid on disuse osteoporosis studied in dogs. Acta Orthopaedica Scandinavica, 62:238-243. 121...bovine serum, 1% antibiotics, and 50 pg/ml ascorbic acid in 100% humidity at 37oC. Prostaglandin E2 was added to confluent, fourth passage cultures... acid from membrane phospholipids. This, in turn, may lead to the formation of prostaglandins, thromboxanes and prostacyclins through the metabolism of

  11. Extra-amniotic prostaglandin E2 and the unfavourable cervix.

    PubMed

    Shepherd, J; Sims, C; Craft, I

    1976-10-02

    A small dose of prostaglandin E2 suspended in a viscous medium was instilled as a single application into the extra-amniotic space of patients with unfavourable induction features the day before planned induction in an attempt to improve the condition of the cervix. Two groups of 15 patients were studied, one receiving prostaglandin E2 250 mug suspended in methyl ethyl cellulose ('Tylose') 6% solution, and the other tylose alone. Cervical status did not change in those receiving tylose alone, whereas a significant improvement occurred in 14 out of 15 patients receiving the prostaglandin. Labour began before formal induction in 1 patient receiving tylose and in 8 receiving prostaglandin.

  12. The low molecular weight fraction of human serum albumin upregulates COX2, prostaglandin E2, and prostaglandin D2 under inflammatory conditions in osteoarthritic knee synovial fibroblasts.

    PubMed

    Frederick, Elizabeth D; Hausburg, Melissa A; Thomas, Gregory W; Rael, Leonard T; Brody, Edward; Bar-Or, David

    2016-12-01

    The ability to decrease inflammation and promote healing is important in the intervention and management of a variety of disease states, including osteoarthritis of the knee (OAK). Even though cyclooxygenase 2 (COX2) has an established pro-inflammatory role, evidence suggests it is also critical to the resolution that occurs after the initial activation phase of the immune response. In this study, we investigated the effects of the low molecular weight fraction of 5% human serum albumin (LMWF-5A), an agent that has proven to decrease pain and improve function in OAK patients after intra-articular injection, on the expression of COX2 and its downstream products, prostaglandins (PGs). Fibroblast-like synoviocytes from the synovial membrane of OAK patients were treated with LMWF-5A or saline as a control with or without the addition of interleukin-1β (IL-1β) or tumor necrosis factor α (TNFα) to elicit an inflammatory response. Cells were harvested for RNA and protein at 2, 4, 8, 12, and 24 h, and media was collected at 24 h for analysis of secreted products. COX2 mRNA expression was determined by qPCR, and COX2 protein expression was determined by western blot analysis. Levels of prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2) in the media were quantified by competitive ELISA. In the presence of either IL-1β or TNFα, LMWF-5A increased the expression of both COX2 mRNA and protein, and this increase was significant compared to that observed with IL-1β- or TNFα-stimulated, saline-treated cells. Downstream of COX2, the levels of PGE2 were increased only in TNFα-stimulated, LMWF-5A-treated cells; however, in both IL-1β- and TNFα-stimulated cells, LMWF-5A increased the release of the anti-inflammatory prostaglandin PGD2. LMWF-5A appears to trigger increased anti-inflammatory PG signaling, and this may be a primary component of its therapeutic mode of action in the treatment of OAK.

  13. UVB light upregulates prostaglandin synthases and prostaglandin receptors in mouse keratinocytes

    SciTech Connect

    Black, Adrienne T.; Gray, Joshua P.; Shakarjian, Michael P.; Mishin, Vladimir; Laskin, Debra L.; Heck, Diane E.; Laskin, Jeffrey D.

    2008-10-01

    Prostaglandins belong to a class of cyclic lipid-derived mediators synthesized from arachidonic acid via COX-1, COX-2 and various prostaglandin synthases. Members of this family include prostaglandins such as PGE{sub 2}, PGF{sub 2{alpha}}, PGD{sub 2} and PGI{sub 2} (prostacyclin) as well as thromboxane. In the present studies we analyzed the effects of UVB on prostaglandin production and prostaglandin synthase expression in primary cultures of undifferentiated and calcium-differentiated mouse keratinocytes. Both cell types were found to constitutively synthesize PGE{sub 2}, PGD{sub 2} and the PGD{sub 2} metabolite PGJ{sub 2}. Twenty-four hours after treatment with UVB (25 mJ/cm{sup 2}), production of PGE{sub 2} and PGJ{sub 2} increased, while PGD{sub 2} production decreased. This was associated with increased expression of COX-2 mRNA and protein. UVB (2.5-25 mJ/cm{sup 2}) also caused marked increases in mRNA expression for the prostanoid synthases PGDS, mPGES-1, mPGES-2, PGFS and PGIS, as well as expression of receptors for PGE{sub 2} (EP1 and EP2), PGD{sub 2} (DP and CRTH2) and prostacyclin (IP). UVB was more effective in inducing COX-2 and DP in differentiated cells and EP1 and IP in undifferentiated cells. UVB readily activated keratinocyte PI-3-kinase (PI3K)/Akt, JNK and p38 MAP signaling pathways which are known to regulate COX-2 expression. While inhibition of PI3K suppressed UVB-induced mPGES-1 and CRTH2 expression, JNK inhibition suppressed mPGES-1, PGIS, EP2 and CRTH2, and p38 kinase inhibition only suppressed EP1 and EP2. These data indicate that UVB modulates expression of prostaglandin synthases and receptors by distinct mechanisms. Moreover, both the capacity of keratinocytes to generate prostaglandins and their ability to respond to these lipid mediators are stimulated by exposure to UVB.

  14. Interplay between the prostaglandin transporter OATP2A1 and prostaglandin E2-mediated cellular effects.

    PubMed

    Bujok, Krystyna; Glaeser, Hartmut; Schuh, Wolfgang; Rau, Tilman T; Schmidt, Ingrid; Fromm, Martin F; Mandery, Kathrin

    2015-03-01

    Prostaglandins such as prostaglandin E2 (PGE2) play a pivotal role in physiological and pathophysiological pathways in gastric mucosa. Little is known about the interrelation of the prostaglandin E (EP) receptors with the prostaglandin transporter OATP2A1 in the gastric mucosa and gastric carcinoma. Therefore, we first investigated the expression of OATP2A1 and EP4 in normal and carcinoma gastric mucosa. Different PGE2-mediated cellular pathways and mechanisms were investigated using human embryonic kidney cells (HEK293) and the human gastric carcinoma cell line AGS stably transfected with OATP2A1. Colocalization and expression of OATP2A1 and EP4 were detected in mucosa of normal gastric tissue and of gastric carcinomas. OATP2A1 reduced the PGE2-mediated cAMP production in HEK293 and AGS cells overexpressing EP4 and OATP2A1. The expression of OATP2A1 in AGS cells resulted in a reduction of [(3)H]-thymidine incorporation which was in line with a higher accumulation of AGS-OATP2A1 cells in S-phase of the cell cycle compared to control cells. In contrast, the expression of OATP2A1 in HEK293 cells had no influence on the distribution in the S-phase compared to control cells. OATP2A1 also diminished the PGE2-mediated expression of interleukin-8 mRNA (IL-8) and hypoxia-inducible-factor 1α (HIF1α) protein in AGS-OATP2A1 cells. The expression of OATP2A1 increased the sensitivity of AGS cells against irinotecan which led to reduced cell viability. Taken together, these data show that OATP2A1 influences PGE2-mediated cellular pathways. Therefore, OATP2A1 needs to be considered as a key determinant for the understanding of the physiology and pathophysiology of prostaglandins in healthy and tumorous gastric mucosa.

  15. Opinion Elicitation in Second Life

    NASA Astrophysics Data System (ADS)

    van Vliet, Marijn; Neviarouskaya, Alena; Prendinger, Helmut

    The paper describes a novel method for opinion elicitation, which is based on the popular 3D online world of “Second Life”. Here people, as avatars, are put into a somewhat realistic context related to the topic for which opinions are sought. We hypothesize that this kind of concrete, interactive context supports the evocation of opinions better than non-context methods, e.g. only showing related images. To confirm our hypothesis, we conducted a small pilot study, which compares the influence of static and interactive context methods on the opinions expressed by subjects. The opinion elicitation scenario in Second Life is supported by the automatic retrieval of opinions from the web. The results of a study indicate that subjects show more reasoned opinions in the interactive condition. A demo illustrating the content of this paper is available.

  16. Requirements Elicitation Using Paper Prototype

    NASA Astrophysics Data System (ADS)

    Vijayan, Jaya; Raju, G.

    Requirements engineering is both the hardest and critical part of software development since errors at this beginning stage propagate through the development process and are the hardest to repair later. This paper proposes an improved approach for requirements elicitation using paper prototype. The paper progresses through an assessment of the new approach using student projects developed for various organizations. The scope of implementation of paper prototype and its advantages are unveiled.

  17. Urea-prostaglandin versus hypertonic saline for instillation abortion.

    PubMed

    Binkin, N J; Schulz, K F; Grimes, D A; Cates, W

    1983-08-15

    Authorities have suggested use of a combination of hyperosmolar urea and low-dose prostaglandin F2 alpha as a second-trimester intra-amniotic abortifacient to avoid the disadvantages of hypertonic saline solution. To examine the safety and efficacy of urea-prostaglandin compared with the instillation of saline solution, we analyzed data from a prospective multicenter study conducted in the United States between 1975 and 1978. Both agents were highly effective in producing an abortion. However, urea-prostaglandin had a significantly lower rate of serious complications when compared with saline solution (1.03 versus 2.18 per 100 abortions; p less than 0.001). Urea-prostaglandin also had a significantly shorter induction-to-abortion time (14.2 versus 25.6 hours; p less than 0.001). Urea-prostaglandin, therefore, appears to be superior to hypertonic saline solution as an abortifacient.

  18. Immunosuppression and human cancer: role of prostaglandins.

    PubMed

    Harvey, H A; Allegra, J C; Demers, L M; Luderer, J R; Brenner, D E; Trautlein, J J; White, D S; Gillin, M A; Lipton, A

    1977-06-01

    Prostaglandins, unsaturated fatty acid derivatives with diversified pharmacologic activity, have been implicated in the pathophysiology of many diseases. Prostaglandin E (PGE) levels were measured by radioimmunoassay in the plasma of 41 normocalcemic patients with various stages of malignancies. Delayed hypersensitivity was assessed by a battery of six recall skin test antigens (ST) and by Dinitrochlorobenzene (DNCB) sensitization and challenge. Twenty-five patients with one or more positive skin tests had a mean PGE level of 87+/-8 pg/ml, whereas 16 patients with negative ST had a mean PGE level of 96+/-12 pg/ml. Twenty-one DNCB negative patients had a mean PGE level of 98+/-12 pg/ml and eight totally anergic patients had a mean PGE of 96+/-12 pg/ml. All PGE values were within the normal range and there was no statistical difference between the four groups. (p less than 0.1). We concluded that circulating PGE does not correlate with the non-specific immunosuppression seen in cancer patients.

  19. Acetylation of prostaglandin synthase by aspirin.

    PubMed Central

    Roth, G J; Stanford, N; Majerus, P W

    1975-01-01

    When microsomes of sheep or bovine seminal vesicles are incubated with [acetyl-3H]aspirin (acetyl salicylic acid), 200 Ci/mol, we observe acetylation of a single protein, as measured by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The protein has a molecular weight of 85,000 and corresponds to a similar acetylated protein found in the particulate fraction of aspirin-treated human platelets. The aspirin-mediated acetylation reaction proceeds with the same time course and at the same concentration as does the inhibition of prostaglandin synthase (cyclo-oxygenase) (EC 1.14.99.1; 8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase) by the drug. At 100 muM aspirin, 50% inhibition of prostaglandin synthase and 50% of maximal acetylation are observed after 15 min at 37 degrees. Furthermore, the substrate for cyclo-oxygenase, arachidonic acid, inhibits protein acetylation by aspirin at concentrations (50% inhibition at 10-30 muM) which correlate with the Michaelis constant of arachidonic acid as a substrate for cyclooxygenase. Arachidonic acid analogues and indomethacin inhibit the acetylation reaction in proportion to their effectiveness as cyclo-oxygenase inhibitors. The results suggest that aspirin acts as an active-site acetylating agent for the enzyme cyclo-oxygenase. This action of aspirin may account for its anti-inflammatory and anti-platelet action. PMID:810797

  20. Prostaglandins, renin, aldosterone, and catecholamines in preeclampsia.

    PubMed

    Pedersen, E B; Christensen, N J; Christensen, P; Johannesen, P; Kornerup, H J; Kristensen, S; Lauritsen, J G; Leyssac, P P; Rasmussen, A B; Wohlert, M

    1983-01-01

    Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin (PRC), aldosterone (PAC), noradrenaline (PNA) and adrenaline (PA) were determined in the third trimester of pregnancy, 5 days and 3 months after delivery in preeclampsia and normotensive pregnant and non-pregnant control subjects. PGE2 was higher in pregnant control subjects than in non-pregnant subjects, but reduced to non-pregnant level in preeclampsia. PGF2 alpha was the same in preeclampsia and normotensive pregnancy but higher than in the non-pregnant group. PRC and PAC were increased during pregnancy, but considerably lesser in preeclampsia than during normotensive pregnancy. PNA and PA were the same in all three groups. All parameters were normal 3 months after delivery. There were no correlations between any of the hormones and blood pressure in any of the groups. PGE2 was positively correlated to PRC. The lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion, and the changes in PRC and PAC are supposed to be secondary to changes in PGE2. It is hypothesised that preeclampsia is a state of prostaglandin deficiency.

  1. [Prostaglandins, insulin secretion and diabetes mellitus].

    PubMed

    Giugliano, D; Torella, R; Scheen, A J; Lefebvre, P J; D'Onofrio, F

    1988-12-01

    The islets of Langerhans have the enzymatic equipment permitting the synthesis of the metabolites of arachidonic acid: cyclo-oxygenase and lipo-oxygenase. Numerous studies have shown that cyclo-oxygenase derivatives, mainly PGE2, reduce the insulin response to glucose whereas lipo-oxygenase derivatives, mainly 15-HPETE, stimulate insulin secretion. So, for instance, drugs that increase prostaglandins synthesis as colchicine or furosemide inhibit insulin secretion while non steroid anti-inflammator drugs, mainly salicylates, which inhibit cyclo-oxygenase, enhance the insulin response to various stimuli. In type-2 (non insulin-dependent) diabetes, an increased sensitivity to endogenous prostaglandins has been proposed as a possible cause for the insulin secretion defect which characterizes this disease. Play in favor of this hypothesis the fact that the administration of PGE inhibits the insulin response to arginine in type-2 diabetics but not in normal subject and the fact that the administration of salicylates could improve the insulin response to glucose in some of these patients.

  2. Involvement of prostaglandins in inflammation induced by latex of Calotropis procera.

    PubMed Central

    Kumar, Vijay L; Shivkar, Yatin M

    2004-01-01

    INTRODUCTION:The aerial parts of the plant Calotropis procera produce milky white latex that causes inflammation of the skin and mucous membranes. Prostaglandins are one of the mediators released in an inflammatory response following induction of cyclooxygenase (COX). In the present study, we have evaluated the role of prostaglandins in inflammatory response elicited by the latex of C. procera. METHODS: Aqueous extract of dried latex of C. procera was injected into the 6-day air-pouch in the rat. The inflammatory response was evaluated by studying the air-pouch fluid for its volume, protein and prostaglandin (PG) E2 concentrations, and leucocyte counts. The granulation tissue from the pouch was quantified and studied for COX-2 expression by reverse transcriptase-polymerase chain reaction. The inhibitory effect of celecoxib and dexamethasone was evaluated on the aforementioned parameters. RESULTS: Dried latex produced an inflammatory response that was maximum at 6 h. It was associated with the accumulation of protein-rich fluid, leucocytes and PGE2 production. It also resulted in granulation of the pouch cavity that was a maximum on day 3. COX-2 expression could be detected in the granulation tissue on day 1 and it increased progressively up to day 5. The anti-inflammatory drugs celecoxib and dexamethasone significantly attenuated the inflammatory response and inhibited COX-2 expression in granulation tissue. CONCLUSIONS: Latex of C. procera induces an inflammatory response characterized by an early exudative phase accompanied by PGE2 production and a late proliferative phase associated with COX-2 induction. Both the phases were effectively inhibited by COX-2 inhibitors. PMID:15223605

  3. Involvement of prostaglandins in inflammation induced by latex of Calotropis procera.

    PubMed

    Kumar, Vijay L; Shivkar, Yatin M

    2004-06-01

    The aerial parts of the plant Calotropis procera produce milky white latex that causes inflammation of the skin and mucous membranes. Prostaglandins are one of the mediators released in an inflammatory response following induction of cyclooxygenase (COX). In the present study, we have evaluated the role of prostaglandins in inflammatory response elicited by the latex of C. procera. Aqueous extract of dried latex of C. procera was injected into the 6-day air-pouch in the rat. The inflammatory response was evaluated by studying the air-pouch fluid for its volume, protein and prostaglandin (PG) E2 concentrations, and leucocyte counts. The granulation tissue from the pouch was quantified and studied for COX-2 expression by reverse transcriptase-polymerase chain reaction. The inhibitory effect of celecoxib and dexamethasone was evaluated on the aforementioned parameters. Dried latex produced an inflammatory response that was maximum at 6 h. It was associated with the accumulation of protein-rich fluid, leucocytes and PGE2 production. It also resulted in granulation of the pouch cavity that was a maximum on day 3. COX-2 expression could be detected in the granulation tissue on day 1 and it increased progressively up to day 5. The anti-inflammatory drugs celecoxib and dexamethasone significantly attenuated the inflammatory response and inhibited COX-2 expression in granulation tissue. Latex of C. procera induces an inflammatory response characterized by an early exudative phase accompanied by PGE2 production and a late proliferative phase associated with COX-2 induction. Both the phases were effectively inhibited by COX-2 inhibitors.

  4. Prostaglandin F2 alpha-induced response of the bovine ovary, oviduct (uterine tube), and uterus.

    PubMed

    Singh, L P; Sadiku, A; Verma, O P

    1979-12-01

    Tissue strips from the ovary, (uterine tube), and oviduct, and uterus of pregnant and nonpregnant cows were tested for their contractile response to prostaglandin F2 alpha (PGF2 alpha). When 2.1 x 10(-6)M PGF2 alpha was added to the uterine strips, tension of tissues from pregnant cows increased sharply; however, tension in tissues from nonpregnant cows only increased moderately. Similar concentrations failed to elicit any response from oviductal tissues of either group. Unlike the uterus and the oviduct, the ovaries contracted slowly and irregularly. They responded with varying degrees of stimulation; ovaries from pregnant cows with brief and mild stimulation and ovaries from nonpregnant cows with slower and relatively stronger stimulation. Results indicate that the bovine ovary contracts rhythmically and that its sensitivity to PGF2 alpha decreases during pregnancy in contrast to the bovine uterus which becomes increasingly sensitive during pregnancy.

  5. Suppression of newborn natural killer cell activity by prostaglandin E2

    SciTech Connect

    Milch, P.O.; Salvatore, W.; Luft, B.; Baker, D.A.

    1988-10-01

    The effect of prostaglandin E2 on natural killer cell activity of cord blood was examined. Natural killer cell activity, determined by chromium 51 release, was significantly reduced after prostaglandin E2 (1 microgram/ml) treatment. Prostaglandin E2 has been found to enhance the cellular spread of herpesvirus. Thus prostaglandins may enhance viral infections indirectly by suppressing natural killer cell activity.

  6. Prostaglandins for prelabour rupture of membranes at or near term.

    PubMed

    Tan, B P; Hannah, M E

    2000-01-01

    Induction of labour after prelabour rupture of membranes may reduce the risk of neonatal infection. However an expectant approach may be less likely to result in caesarean section. The objective of this review was to assess the effects of induction of labour with prostaglandins versus expectant management for prelabour rupture of membranes at or near term. We searched the Cochrane Pregnancy and Childbirth Group trials register. Randomised and quasi-randomised trials comparing early use of prostaglandins (with or without oxytocin) with no early use of prostaglandins in women with spontaneous rupture of membranes before labour, and 34 weeks or more of gestation. Trials were assessed for quality and data were abstracted. Fifteen trials were included. Most were of moderate to good quality. Different forms of prostaglandin preparations were used in these trials and it may be inappropriate to combine their results. Induction of labour by prostaglandins was associated with a decreased risk of chorioamnionitis (odds ratio 0.77, 95% confidence interval 0.61 to 0.97) based on eight trials and admission to neonatal intensive care (odds ratio 0.79, 95% confidence interval 0. 66 to 0.94) based on seven trials. No difference was detected for rate of caesarean section, although induction by prostaglandins was associated with a more frequent maternal diarrhoea and use of anaesthesia and/or analgesia. Based on one trial, women were more likely to view their care positively if labour was induced with prostaglandins,. Induction of labour with prostaglandins appears to decrease the risk of maternal infection (chorioamnionitis) and admission to neonatal intensive care. Induction of labour with prostaglandins does not appear to increase the rate of caesarean section, although it is associated with more frequent maternal diarrhoea and pain relief.

  7. Prostaglandin dehydrogenase and the initiation of labor.

    PubMed

    Challis, J R; Patel, F A; Pomini, F

    1999-01-01

    In summary, these studies have suggested that prostaglandin dehydrogenase may have a central role to play in the mechanisms which determine biologically active prostaglandin concentrations within human fetal membranes and placenta at the time of labor, at term or preterm. Moreover, our studies indicate that the regulation of PGDH may by multifactorial (figure 3). In certain regions of the membranes, we suggest that PGDH expression may be influenced by levels of anti-inflammatory and pro-inflammatory cytokines. In other regions of the membranes, we suggest that PGDH may be regulated at a transcriptional level by competing activities of progesterone and cortisol. The action of progesterone could be effected through systemically-derived steroid, or by locally synthesized steroid, acting in a paracrine and/or autocrine fashion. The effects of cortisol in placenta must be due to glucocorticoid derived from the maternal or fetal compartment, since the placenta lacks the hydroxylases required for endogenous cortisol production. However, metabolism of cortisol by 11 beta-HSD-2 reduces the potency of this glucocorticoid in placental tissue. In chorion however, cortisol may be formed locally, from cortisone, in addition to its being derived from the maternal circulation and/or from the amniotic fluid. Our current studies do not allow us to delineate whether the effects of progesterone and cortisol on PGDH are exerted through the glucocorticoid receptor (GR) or progesterone receptor (PR) or both. It is possible that through pregnancy, PGDH activity is maintained by progesterone acting either through low levels of PR in membranes, or, more likely, acting through GR. At term, elevated levels of cortisol compete with and displace progesterone from GR, resulting in inhibition of PGDH transcription and activity. In this way, local withdrawal of progesterone action would be effected within human intrauterine tissues, without requiring changes in systemic, circulating progesterone

  8. Biologic interaction of prostaglandin, thromboxane and prostacyclin: potential clinical applications.

    PubMed

    Bell, T G; Smith, W L; Oxender, W D

    1986-01-01

    Prostaglandins are vasoactive agents which have potent and varied effects depending on the species, conditions and organs tested. The clinician wishing to gain a significant overview of the field from current research literature has a demanding task for himself. A review of biologic interactions is exactly what is needed in a consideration of possible clinical applications of prostaglandins. Thus, it is necessary first to recount the last five years' advances in prostaglandin research. Only then will the listing and discussion of some diseases soon to benefit from the application of research be meaningful.

  9. Reduction in urinary prostaglandin excretion in the premenstrual syndrome.

    PubMed

    Piccoli, A; Modena, F; Calò, L; Cantaro, S; Avogadro, A; Nardo, G; Cerutti, R

    1993-12-01

    The purpose of the present work was to study some factors involved in renal handling of salt and water in the premenstrual syndrome (PMS), in which salt and water retention is frequently observed. In 18 women with PMS and in 18 healthy women we studied the levels of cyclic adenosine monophosphate, aldosterone, prostaglandin E2, prostaglandin F2 alpha and kallikrein in urinary samples collected during the luteal phase. There was no difference between the two groups regarding sodium, aldosterone and kallikrein urinary excretion. In the PMS group there was a significant reduction in urinary excretion of cyclic adenosine monophosphate, prostaglandin E2 and prostaglandin F2 alpha with respect to the control group. At multivariate analysis sodium urinary excretion proved not to be the same as the model validated in healthy women. There may be different renal handling of water and electrolytes during the luteal phase of the menstrual cycle in women with PMS.

  10. Use of vaginal prostaglandin gel before induction of labour.

    PubMed

    Murphy, A J; Jalland, M; Pepperell, R J; Quinn, M A

    1980-05-01

    Tylose gel containing either 1.5 mg, 3.0 mg or 10.0 mg of prostaglandin F2 alpha was inserted into the posterior vaginal fornix of 165 patients on the evening before induction of labour. A control group of 100 patients received the gel alone. There was a significant reduction in the induction-delivery interval in nulliparae receiving at least 3.0 mg of prostaglandin, whereas, in multiparae all doses achieved this effect. There was also a significant reduction in the incidence of forceps delivery in nulliparae who received 3.0 mg or more of the prostaglandin gel; however, there was no difference in the incidence of spontneous labour, epidural anaesthesia or Caesarean section between the patients who received prostaglandin or those receiving gel alone.

  11. Insulin/FOXO Signaling Regulates Ovarian Prostaglandins Critical for Reproduction

    PubMed Central

    Edmonds, Johnathan W.; Prasain, Jeevan K.; Dorand, Dixon; Yang, Youfeng; Hoang, Hieu D.; Vibbert, Jack; Kubagawa, Homare M.; Miller, Michael A.

    2010-01-01

    SUMMARY Abnormalities in insulin/IGF-1 signaling are associated with infertility, but the molecular mechanisms are not well understood. Here we use liquid chromatography with electrospray ionization tandem mass spectrometry to show that the C. elegans insulin/FOXO pathway regulates the metabolism of locally acting lipid hormones called prostaglandins. C. elegans prostaglandins are synthesized without prostaglandin G/H synthase homologs, the targets of non-steroidal anti-inflammatory drugs. Our results support the model that insulin signaling promotes the conversion of oocyte polyunsaturated fatty acids (PUFAs) into F-series prostaglandins that guide sperm to the fertilization site. Reduction in insulin signaling activates DAF-16/FOXO, which represses the transcription of germline and intestinal genes required to deliver PUFAs to oocytes in lipoprotein complexes. Nutritional and neuroendocrine cues target this mechanism to control prostaglandin metabolism and reproductive output. Prostaglandins may be conserved sperm guidance factors and widespread downstream effectors of insulin actions that influence both reproductive and nonreproductive processes. PMID:21145501

  12. Prostaglandins in Cancer Cell Adhesion, Migration, and Invasion

    PubMed Central

    Menter, David G.; DuBois, Raymond N.

    2012-01-01

    Prostaglandins exert a profound influence over the adhesive, migratory, and invasive behavior of cells during the development and progression of cancer. Cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) are upregulated in inflammation and cancer. This results in the production of prostaglandin E2 (PGE2), which binds to and activates G-protein-coupled prostaglandin E1–4 receptors (EP1–4). Selectively targeting the COX-2/mPGES-1/PGE2/EP1–4 axis of the prostaglandin pathway can reduce the adhesion, migration, invasion, and angiogenesis. Once stimulated by prostaglandins, cadherin adhesive connections between epithelial or endothelial cells are lost. This enables cells to invade through the underlying basement membrane and extracellular matrix (ECM). Interactions with the ECM are mediated by cell surface integrins by “outside-in signaling” through Src and focal adhesion kinase (FAK) and/or “inside-out signaling” through talins and kindlins. Combining the use of COX-2/mPGES-1/PGE2/EP1–4 axis-targeted molecules with those targeting cell surface adhesion receptors or their downstream signaling molecules may enhance cancer therapy. PMID:22505934

  13. Role of seminal prostaglandins in male fertility. II. Effects of prostaglandin synthesis inhibition on spermatogenesis in man.

    PubMed

    Conte, D; Nordio, M; Romanelli, F; Manganelli, F; Giovenco, P; Dondero, F; Isidori, A

    1985-08-01

    The effect of prostaglandin biosynthesis inhibition has been studied in two groups of infertile oligozoospermic patients with high or normal-low seminal prostaglandin (PG) levels. PGE and 19-OH PGE were assayed by means of a gas chromatographic method and the most important seminal parameters (volume, concentration, motility and morphology of spermatozoa) were evaluated in basal conditions and at the end of indomethacin treatment, at a daily oral dose of 100 mg for thirty days. A drop in prostaglandin levels following indomethacin was observed in both groups of patients but only in the group with high concentrations of prostanoid derivates the prostaglandin inhibition was correlated with a significant improvement in sperm count and motility.

  14. The occurrence of 15-keto-prostaglandins in the red alga Gracilaria verrucosa.

    PubMed

    Dang, The Hung; Lee, Hye Ja; Yoo, Eun Sook; Hong, Jongki; Choi, Jae Sue; Jung, Jee H

    2010-09-01

    New 15-keto-prostaglandins (1-4) were isolated from the MeOH extract of the red alga, Gracilaria verrucosa. Their structures were determined to be prostaglandin B congeners (1-3) and a prostaglandin E congener (4) based on the NMR and MS data. Prostaglandins with a C-15 keto function are rare from natural sources. The presence of these metabolites in the alga is notable because 15-keto-prostaglandins (15-keto-PGs) are considered to be the metabolic products of regular prostaglandins in mammals. The occurrence of different prostaglandins in this alga might be due to the existence of different oxidative enzymes, as previously mentioned for oxygenated fatty acids of the red alga Gracilariopsis lemaneiformis. The antiinflammatory activity of these prostaglandins was examined by evaluating their inhibitory effects on nitric oxide production in lipopolysaccharide (LPS)-activated RAW264.7 murine macrophage cells. These prostaglandins showed weak activity on nitric oxide production.

  15. Prostaglandin content of tissue lining vascular prostheses

    SciTech Connect

    Greisler, H.P.; Kim, D.U.; Nussbaum, M.; Ellinger, J.; Schwarcz, T.H.

    1986-03-01

    This laboratory previously demonstrated arterial regeneration with a confluent endothelial-like flow surface 3-4 weeks after interposition of absorbable prostheses but not of dacron prostheses into the rabbit aorta. This study evaluates prostaglandin contents of inner capsular tissues within arterial prostheses. 6-keto-PGF/sub 1..cap alpha../ and TxB/sub 2/ were assayed (/sup 3/H-RIA) in supernatants of sonicated homogenates of tissues on the inner aspect of (a) absorbable polydioxanone (PDS), (b) absorbable polyglactin 910 (PG910), or (c) compound dacron-PG910 prostheses 3 or 6 months following implantation into rabbit aortas. Normal aortic controls from each rabbit were similarly treated. The 6-keto-PGF/sub 1..cap alpha../ values for all groups were lower than normal controls (p < .05). The ratio 6-keto-PGF/sub 1..cap alpha..//TxB/sub 2/ for PDS was nearly identical to normal aorta (1.69 +/- .54). This study shows that the quantity and ratio of eicosanoids in the inner capsular tissues is modified by the composition of the implanted arterial prosthesis.

  16. Simulated microgravity upregulates an endothelial vasoconstrictor prostaglandin

    NASA Technical Reports Server (NTRS)

    Sangha, D. S.; Han, S.; Purdy, R. E.

    2001-01-01

    Endothelial nitric oxide contributes to the vascular hyporesponsiveness to norepinephrine (NE) observed in carotid arteries from rats exposed to simulated microgravity. The goal of the present study was to determine whether a cyclooxygenase product of arachidonic acid also influences vascular responsiveness in this setting. Microgravity was simulated in rats by hindlimb unweighting (HU). After 20 days of HU, carotid arteries were isolated from control and HU-treated rats, and vascular rings were mounted in tissue baths for the measurement of isometric contraction. Two cyclooxygenase inhibitors, indomethacin and ibuprofen, and the selective thromboxane A(2) prostanoid-receptor antagonist, SQ-29548, had no effect on the contraction to NE in control vessels but markedly reduced contraction to NE in HU vessels. When the endothelium was removed, indomethacin no longer had any effect on the NE-induced contraction in HU vessels. In endothelium-intact vessels in the presence of indomethacin, the addition of the nitric oxide synthase inhibitor, N(G)-L-nitro-arginine methyl ester, to the medium bathing HU vessels increased the contraction to NE to the level of that of the control vessels. These results indicate that HU treatment induced two endothelial changes in carotid artery that opposed each other. Nitric oxide activity was increased and was responsible for the vascular hyporesponsiveness to NE. The activity of a vasoconstrictor prostaglandin was also increased, and attenuated the vasodilating effect of nitric oxide.

  17. Subcutaneous fat necrosis, hypercalcemia, and prostaglandin E.

    PubMed

    Sharata, H; Postellon, D C; Hashimoto, K

    1995-03-01

    We present two patients with subcutaneous fat necroses (SCFN) in whom endocrinologic studies revealed an association with elevated prostaglandin E (PGE) levels. A boy born after prolonged labor complicated by meconium aspiration developed erythematous, indurated plaques over the back, arms, buttocks, and cheeks at 4 days of age. A biopsy specimen of involved skin showed panniculitis with foci of necrotic adipocytes containing radially arranged, needle-shaped clefts and a granulomatous infiltrate in the septae. Laboratory studies revealed hypercalcemia of 13.6 mg/dl (normal 8.8-10.1 mg/dl), elevated 1.25-1.25(OH)2D3, and increased urinary excretion of PGE2. The child was hospitalized and treated with systemic steroids and diuretics, with resolution of SCFN and hypercalcemia. The second patient was a girl born with cyanotic heart disease. A diagnosis of Ebstein anomaly was made, and intravenous PGE1 was started to keep patent the ductus arteriosus. Four days later erythematous, indurated plaques were noted on the knee, back, and anterior chest. A skin biopsy specimen revealed SCFN. There was no associated laboratory abnormality. On discontinuing PGE1, no new lesions formed and the existing panniculitis resolved. These two cases demonstrate the association between SCFN and elevated PGE levels (endogenous in patient 1, exogenous in patient 2). No previous reports of SCFN after the administration of PGE1 have appeared in the literature.

  18. Prostaglandin analogs in the treatment of glaucoma.

    PubMed

    Hejkal, T W; Camras, C B

    1999-09-01

    Prostaglandin (PG) analogs are some of the most recent additions to the list of ocular hypotensive medications. Two analogs of naturally occurring PGs are available commercially, isopropyl unoprostone (Rescula [Ciba Vision, Atlanta, GA]) and latanoprost (Xalatan [Pharmacia & Upjohn, Bridgewater, NJ]). Presently, latanoprost 0. 005% is the only PG analog commercially available in the United States. These agents have been shown to be the most effective topical medications for reducing intraocular pressure. They have a different mechanism of action than other ocular hypotensives, and act primarily by increasing uveoscleral outflow. Because of this, PGs have a substantial additive effect when used with agents that reduce aqueous production (eg, beta blockers or carbonic anhydrase inhibitors) or that increase trabecular outflow facility (eg, pilocarpine). Local side effects include mild conjunctival hyperemia and local irritation, darkening of iris color, increased growth of eyelashes, and a possible association with cystoid macular edema or iritis in some patients with other risk factors. No systemic side effects have been proven to be caused by latanoprost. Recommended dosing is once daily at bedtime.

  19. Prostaglandins as PPARγ Modulators in Adipogenesis

    PubMed Central

    Fujimori, Ko

    2012-01-01

    Adipocytes and fat cells play critical roles in the regulation of energy homeostasis. Adipogenesis (adipocyte differentiation) is regulated via a complex process including coordinated changes in hormone sensitivity and gene expression. PPARγ is a ligand-dependent transcription factor and important in adipogenesis, as it enhances the expression of numerous adipogenic and lipogenic genes in adipocytes. Prostaglandins (PGs), which are lipid mediators, are associated with the regulation of PPARγ function in adipocytes. Prostacyclin promotes the differentiation of adipocyte-precursor cells to adipose cells via activation of the expression of C/EBPβ and δ. These proteins are important transcription factors in the activation of the early phase of adipogenesis, and they activate the expression of PPARγ, which event precedes the maturation of adipocytes. PGE2 and PGF2α strongly suppress the early phase of adipocyte differentiation by enhancing their own production via receptor-mediated elevation of the expression of cycloxygenase-2, and they also suppress the function of PPARγ. In contrast, PGD2 and its non-enzymatic metabolite, Δ12-PGJ2, activate the middle-late phase of adipocyte differentiation through both DP2 receptors and PPARγ. This paper focuses on potential roles of PGs as PPARγ modulators in adipogenesis and regulators of obesity. PMID:23319937

  20. Pharmacogenomics of Prostaglandin and Leukotriene Receptors

    PubMed Central

    Cornejo-García, José A.; Perkins, James R.; Jurado-Escobar, Raquel; García-Martín, Elena; Agúndez, José A.; Viguera, Enrique; Pérez-Sánchez, Natalia; Blanca-López, Natalia

    2016-01-01

    Individual genetic background together with environmental effects are thought to be behind many human complex diseases. A number of genetic variants, mainly single nucleotide polymorphisms (SNPs), have been shown to be associated with various pathological and inflammatory conditions, representing potential therapeutic targets. Prostaglandins (PTGs) and leukotrienes (LTs) are eicosanoids derived from arachidonic acid and related polyunsaturated fatty acids that participate in both normal homeostasis and inflammatory conditions. These bioactive lipid mediators are synthesized through two major multistep enzymatic pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main physiological effects of PTGs include vasodilation and vascular leakage (PTGE2); mast cell maturation, eosinophil recruitment, and allergic responses (PTGD2); vascular and respiratory smooth muscle contraction (PTGF2), and inhibition of platelet aggregation (PTGI2). LTB4 is mainly involved in neutrophil recruitment, vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs) (LTC4, LTD4, and LTE4) induce bronchoconstriction and neutrophil extravasation, and also participate in vascular leakage. PTGs and LTs exert their biological functions by binding to cognate receptors, which belong to the seven transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding these receptors may influence their functionality and have a role in disease susceptibility and drug treatment response. In this review we summarize SNPs in PTGs and LTs receptors and their relevance in human diseases. We also provide information on gene expression. Finally, we speculate on future directions for this topic. PMID:27708579

  1. Simulated microgravity upregulates an endothelial vasoconstrictor prostaglandin

    NASA Technical Reports Server (NTRS)

    Sangha, D. S.; Han, S.; Purdy, R. E.

    2001-01-01

    Endothelial nitric oxide contributes to the vascular hyporesponsiveness to norepinephrine (NE) observed in carotid arteries from rats exposed to simulated microgravity. The goal of the present study was to determine whether a cyclooxygenase product of arachidonic acid also influences vascular responsiveness in this setting. Microgravity was simulated in rats by hindlimb unweighting (HU). After 20 days of HU, carotid arteries were isolated from control and HU-treated rats, and vascular rings were mounted in tissue baths for the measurement of isometric contraction. Two cyclooxygenase inhibitors, indomethacin and ibuprofen, and the selective thromboxane A(2) prostanoid-receptor antagonist, SQ-29548, had no effect on the contraction to NE in control vessels but markedly reduced contraction to NE in HU vessels. When the endothelium was removed, indomethacin no longer had any effect on the NE-induced contraction in HU vessels. In endothelium-intact vessels in the presence of indomethacin, the addition of the nitric oxide synthase inhibitor, N(G)-L-nitro-arginine methyl ester, to the medium bathing HU vessels increased the contraction to NE to the level of that of the control vessels. These results indicate that HU treatment induced two endothelial changes in carotid artery that opposed each other. Nitric oxide activity was increased and was responsible for the vascular hyporesponsiveness to NE. The activity of a vasoconstrictor prostaglandin was also increased, and attenuated the vasodilating effect of nitric oxide.

  2. Evidence against a physiological role of prostaglandins in the regulation of noradrenaline release in the cat spleen.

    PubMed Central

    Dubocovich, M L; Langer, S Z

    1975-01-01

    1. The effects of prostaglandins E2 (PGE2) and indomethacin on responses and on noradrenaline overflow elicited by nerve stimulation were studied in the perfused cat's spleen, at different calcium concentrations in the perfusion medium: 0-26, 0-65 and 2-6 mve stimulation and in the overflow of the transmitter. PGE2 was more effective in reducing transmitter overflow at 5 than at 30 Hz. 3. Indomethacin, 14-0 muM, prevented the release of PGE-like material in the venous effluent of the spleen elicited by either nerve stimulation or by exogenous noradrenaline. 4. During exposure to 14-0 muM indomethacin there was no increase in responses to nerve stimulation or in the overflow of noradrenaline elicited by nerve stimulation at 5 or at 30 Hz. 5. Similar results to those obtained with exogenous PGE2 and with indomethacin in the presence of 2-6 mM calcium, were observed when the experiments were carried out in the presence of either 0-65 or 0-26 mM calcium. 6. In the presence of the alpha-adrenoceptor blocking agents, phenoxybenzamine (2-9 muM) or phentolamine (3-1 muM), the increase in transmitter overflow obtained during stimulation was 6-5 and 8-3-fold respectively. 7. Since inhibition of the synthesis of PGE did not increase transmitter overflow during nerve stimulation, it appears that the proposed negative feed-back mechanism mediated by endogenous prostaglandins does not play an important physiological role in the regulation of adrenergic neurotransmission in the cat spleen. In this tissue the major endogenous negative feed-back regulatory mechanism is triggered by the neurotransmitter through the activation of prejunctional alpha-adrenoceptors. PMID:171381

  3. Impotence evaluated by the use of prostaglandin E1

    SciTech Connect

    Hwang, T.I.; Yang, C.R.; Wang, S.J.; Chang, C.L.; Tzai, T.S.; Chang, C.H.; Wu, H.C.

    1989-06-01

    We screened 80 patients at our hospital for the differential diagnosis of impotence using intracavernous injection of prostaglandin E1 (20 micrograms). The rate of positive response was 78.8 per cent (63 patients). Neither systemic reactions nor priapism occurred. However, a considerable incidence (23.8 per cent, 19 of 80 patients) of tolerable injection pain was encountered. The 133-xenon penile washout study was conducted routinely in impotent men for hemodynamic evaluation of penile vascularity. In 80 patients a positive correlation between the response of intracavernous prostaglandin E1 injection and the result of the washout study was found (r equals 0.381, p less than 0.0002). We selected 14 subjects randomly to receive additional intravenous infusions of prostaglandin E1 (6 ampules, 120 micrograms total) for 3 days, after which another 133-xenon washout study was done. The washout studies before and after intravenous prostaglandin E1 infusion were compared, and 10 patients (71.4 per cent) appeared to obtain improvement in half-time clearance and penile blood flow. However, only 3 patients noticed improvement subjectively. We suggest that prostaglandin E1 could be a desirable alternative for the diagnosis and treatment of impotence.

  4. Prostaglandins and their receptors in insect biology.

    PubMed

    Stanley, David; Kim, Yonggyun

    2011-01-01

    We treat the biological significance of prostaglandins (PGs) and their known receptors in insect biology. PGs and related eicosanoids are oxygenated derivatives of arachidonic acid (AA) and two other C20 polyunsaturated fatty acids. PGs are mostly appreciated in the context of biomedicine, but a growing body of literature indicates the biological significance of these compounds extends throughout the animal kingdom, and possibly beyond. The actions of most PGs are mediated by specific receptors. Biomedical research has discovered a great deal of knowledge about PG receptors in mammals, including their structures, pharmacology, molecular biology and cellular locations. Studies of PG receptors in insects lag behind the biomedical background, however, recent results hold the promise of accelerated research in this area. A PG receptor has been identified in a class of lepidopteran hemocytes and experimentally linked to the release of prophenoloxidase. PGs act in several crucial areas of insect biology. In reproduction, a specific PG, PGE(2), releases oviposition behavior in most crickets and a few other insect species; PGs also mediate events in egg development in some species, which may represent all insects. PGs play major roles in modulating fluid secretion in Malpighian tubules, rectum and salivary glands, although, again, this has been studied in only a few insect species that may represent the Class. Insect immunity is a very complex defense system. PGs and other eicosanoids mediate a large number of immune reactions to infection and invasion. We conclude that research into PGs and their receptors in insects will lead to important advances in our understanding of insect biology.

  5. Prostaglandin analogues in the treatment of glaucoma.

    PubMed

    Lindén, C; Alm, A

    1999-05-01

    Prostaglandin (PG) analogues are a new class of ocular hypotensive drugs that have been developed for the treatment of open angle glaucoma. Two of these drugs, latanoprost and unoprostone, are presently commercially available. Latanoprost was introduced in 1996 in the US and Europe. Presently it enjoys the most widespread use and is the most well documented drug of this group. It reduces the intraocular pressure (IOP) by a mechanism of action different from other drugs; namely by increasing the uveoscleral outflow. The aqueous inflow is not affected. The optimal dose regimen is one drop of 50 microg/ml once daily, which reduces the IOP by approximately 30% in patients with glaucoma. A more pronounced ocular hypotensive effect is demonstrated when latanoprost is combined with other glaucoma therapies, including beta-blockers, adrenergic and cholinergic agonists or carbonic anhydrase inhibitors. Latanoprost is well tolerated. The drug reaches a plasma concentration below that needed for stimulation of the FP-receptor, which may explain its favourable systemic tolerability profile. The major ocular adverse effect is increased iris pigmentation, which is due to increased synthesis of melanin in the melanocytes of the iris stroma. It is most frequently seen in green-brown eyes and it is probably permanent. A low frequency of cystoid macular oedema has also been reported, predominantly in predisposed eyes. Unoprostone was launched in Japan in 1994, but there is little experience with this drug outside the Japanese market and the documentation is more limited. Its main mechanism of action is on outflow, but this is not yet fully elucidated. The recommended dosage regimen is 1 drop of 1.2 mg/ml twice daily. No comparative studies in humans between the 2 drugs have yet been published.

  6. The role of prostaglandins in reproductive physiology.

    PubMed

    Bardin, T P

    1970-10-01

    Research on the physiopathologic and biochemical nature of prostaglandins (PGs) suggest that PGs play a role in reproductive physiology. In vitro studies show that the PGE series decrease the motility of the human uterus, fallopian tubes, and ureter, and produce vasodilatation. PGFs cause vasoconstriction and increased motility of the uterus, fallopian tubes, ureter, and gastrointestinal muscle. PGs are also known to inhibit lipolysis, platelet aggregation, and gastric secretion. The exact mechanism of PGs are not fully understood, but evidence suggests that many responses can be attributed to interference with the enzyme adenyl cyclase, which catalyzes the formation of adenosine 3',5'-monophosphate (cyclic AMP) from adenosine triphosphate. The adenyl cyclase-cyclic AMP system mediates lipolysis, steroidogenesis, gastric secretion, certain smooth muscle motility responses, and increase in permeability due to vasopressin. Early studies of the myometrial effects of PGs showed that the PGE series inhibited the motility of the human myometrium in vitro while the PGF series produced mixed responses. The role of PGF2alpha in parturition has not been established but evidence suggests that it has a potential role as an oxytocic in cases of therapeutic abortion. In the area of human fertility, the physiologic role of PGs in seminal fluid is hypothesized to facilitate the migration of spermatozoa from the vagina into the uterine cavity. Karolinska Institute researchers have found that some infertile males have low PG levels in their ejaculates and are now working with methods of improving the PG levels to improve their fertility. Pickles et al. proposed a potential role for PGs in the etiology of dysmenorrhea, having found a significantly higher ratio of PGF to PGE in a series of patients with severe dysmenorrhea than in a comparable series of normal patients. The luteolytic and antinidatory effects of PGF2alpha are being investigated and studies appear encouraging. PGs have

  7. Induction of abortion by different prostaglandin analogues.

    PubMed

    Bygdeman, M; Wiqvist, N

    1974-01-01

    The clinical advantages and disadvantages of intra amniotic administration of PGF2alpha in comparison with hypertonic saline has recently been summarized by the Prostaglandin Task Force within the World Health Organization Expanded program. The investigation comprised approximately 1,500 patients treated randomly with the two methods. The main advantage of the PG method was a significantly shorter induction-abortion interval and a lesser risk for serious complications and the significant disadvantage a slight increase in the mean frequency of minor complaints in terms of diarrhoea and vomiting. With PGF2alpha it seems difficult to obtain a "one shot" method to terminate second trimester pregnancy even with the intra-amniotic route of administration. The 15-methyl analogues seem more promising in this respect. The uterine response following administration of this compound is characterized by a more gradual initiation of uterine stimulation and a sustained effect, One intraamniotic injection of 2.5 mg 15-methyl-PGF2alpha induced abortion in nearly 100% of the cases and the incidence of side effects was low. Promising results with this compound have also been obtained following a single extra-amniotic instillation or by repeated intramuscular injections. Vaginal administration of 15-methyl PGF2alpha or its methyl ester can also be used for termination of pregnancy. Recently orally active PG analogues have become available for clinical testing. One of these compounds, 16,16-dimethyl-PGE2 may in some cases stimulate uterine contractility sufficiently to induce a second trimester abortion following repeated oral administration.

  8. Prostaglandins and Their Receptors in Insect Biology

    PubMed Central

    Stanley, David; Kim, Yonggyun

    2011-01-01

    We treat the biological significance of prostaglandins (PGs) and their known receptors in insect biology. PGs and related eicosanoids are oxygenated derivatives of arachidonic acid (AA) and two other C20 polyunsaturated fatty acids. PGs are mostly appreciated in the context of biomedicine, but a growing body of literature indicates the biological significance of these compounds extends throughout the animal kingdom, and possibly beyond. The actions of most PGs are mediated by specific receptors. Biomedical research has discovered a great deal of knowledge about PG receptors in mammals, including their structures, pharmacology, molecular biology and cellular locations. Studies of PG receptors in insects lag behind the biomedical background, however, recent results hold the promise of accelerated research in this area. A PG receptor has been identified in a class of lepidopteran hemocytes and experimentally linked to the release of prophenoloxidase. PGs act in several crucial areas of insect biology. In reproduction, a specific PG, PGE2, releases oviposition behavior in most crickets and a few other insect species; PGs also mediate events in egg development in some species, which may represent all insects. PGs play major roles in modulating fluid secretion in Malpighian tubules, rectum and salivary glands, although, again, this has been studied in only a few insect species that may represent the Class. Insect immunity is a very complex defense system. PGs and other eicosanoids mediate a large number of immune reactions to infection and invasion. We conclude that research into PGs and their receptors in insects will lead to important advances in our understanding of insect biology. PMID:22654840

  9. Prostaglandin E2 inhibits platelet-derived growth factor-stimulated cell proliferation through a prostaglandin E receptor EP2 subtype in rat hepatic stellate cells.

    PubMed

    Koide, Shigeki; Kobayashi, Yoshimasa; Oki, Yutaka; Nakamura, Hirotoshi

    2004-09-01

    Prostaglandin (PG) E2 inhibits hepatic stellate cell (HSC) mitogenesis. PGE-specific receptors are divided into four subtypes that are coupled either to Ca2+ mobilization (EP1 and EP3) or to the stimulation of adenyl cyclase (EP2 and EP4). The aims of the current study were to identify PGE receptor subtypes in cultured rat HSC and to examine which PGE receptor subtype(s) mediates the inhibitory effect of PGE2 on platelet-derived growth factor (PDGF)-stimulated proliferation. Reverse transcription-polymerase chain reaction analysis was performed to detect PGE receptor subtype mRNA expression. Cell proliferation was determined by measuring [3H]thymidine incorporation, and intracellular cyclic AMP was measured by radioimmunoassay. Cultured rat HSC expressed mRNAs for all four subtypes of PGE receptor. PGE2- and EP2-selective agonist produced dose-dependent inhibitory effects on PDGF-stimulated proliferation. Neither EP1-, EP3-, nor EP4-selective agonists showed any inhibitory effect. An adenylate cyclase inhibitor strongly blunted the inhibition of DNA synthesis elicited by PGE2 and the EP2 agonist. The EP2 agonist generated higher and more prolonged increases in intracellular cyclic AMP than the EP4 agonist. Activation of the PGE EP2 receptor has an antiproliferative effect in HSC that may be mediated by cyclic AMP-related signal transduction pathways.

  10. Pro-inflammatory prostaglandins and progression of colorectal cancer

    PubMed Central

    Wang, Dingzhi; DuBois, Raymond N.

    2008-01-01

    Chronic inflammation is a risk factor for several gastrointestinal malignancies, including esophageal, gastric, hepatic, pancreatic and colorectal cancer. It has long been known that long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the relative risk of developing colorectal cancer. NSAIDs exert their anti-inflammatory and anti-tumor effects primarily by inhibiting activity of cyclooxygenase (COX) enzymes. Cyclooxygenase enzymes catalyze the conversion of arachidonic acid into prostanoids, including prostaglandins (PGs) and thromboxanes (TXs). Emerging evidence demonstrates that prostaglandins play an important role in inflammation and cancer. In this review, we highlight recent breakthroughs in our understanding of the roles of the different prostaglandins in colorectal cancer (CRC) and inflammatory bowel disease (IBD). These findings may provide a rationale for the development of new anti-inflammatory therapeutic approaches to cancer prevention and/or treatment. PMID:18406516

  11. Intravaginal prostaglandin-E2 for cervical priming and induction of labour.

    PubMed

    Al-Taani, M I

    2007-01-01

    A prospective study examined the safety, efficacy and labour outcome in 436 women undergoing labour induction using intravaginal prostaglandin E2. Women with singleton pregnancies (235 nulliparas and 201 multiparas) were recruited if they had a clinically unfavourable cervix, and indications for induction. The mean (standard deviation) interval from initiation to delivery was statistically significantly shorter in multiparas than nulliparas: 13.5 hours (SD 1.8) versus 15.5 hours (SD 2.4). No more than 2 x 3 mg tablets were needed to achieve a clinically feasible cervix for amniotomy. The overall need for oxytocin augmentation of labour was 42%, significantly higher in nulliparas (47%) than multiparas (35%). Intrapartum complications, caesarean section and perinatal deaths showed no statistically significant differences between the groups.

  12. Appearance of Prostaglandin F2α in Human Blood during Labour*

    PubMed Central

    Karim, S. M. M.

    1968-01-01

    Blood samples from over 70 pregnant women have been examined for the presence of four prostaglandins. Samples obtained from women not in labour at different gestation periods and at term contained no detectable amounts of prostaglandins. Prostaglandin F2α was present in samples of blood obtained during normal spontaneous labour. The appearance of this substance in the blood preceded the uterine contraction. Whether prostaglandins play a part in the process of normal labour is still conjectural. PMID:5723366

  13. Suppression of Alzheimer-Associated Inflammation by Microglial Prostaglandin-E2 EP4 Receptor Signaling

    PubMed Central

    Woodling, Nathaniel S.; Wang, Qian; Priyam, Prachi G.; Larkin, Paul; Shi, Ju; Johansson, Jenny U.; Zagol-Ikapitte, Irene; Boutaud, Olivier

    2014-01-01

    A persistent and nonresolving inflammatory response to accumulating Aβ peptide species is a cardinal feature in the development of Alzheimer's disease (AD). In response to accumulating Aβ peptide species, microglia, the innate immune cells of the brain, generate a toxic inflammatory response that accelerates synaptic and neuronal injury. Many proinflammatory signaling pathways are linked to progression of neurodegeneration. However, endogenous anti-inflammatory pathways capable of suppressing Aβ-induced inflammation represent a relatively unexplored area. Here we report that signaling through the prostaglandin-E2 (PGE2) EP4 receptor potently suppresses microglial inflammatory responses to Aβ42 peptides. In cultured microglial cells, EP4 stimulation attenuated levels of Aβ42-induced inflammatory factors and potentiated phagocytosis of Aβ42. Microarray analysis demonstrated that EP4 stimulation broadly opposed Aβ42-driven gene expression changes in microglia, with enrichment for targets of IRF1, IRF7, and NF-κB transcription factors. In vivo, conditional deletion of microglial EP4 in APPSwe-PS1ΔE9 (APP-PS1) mice conversely increased inflammatory gene expression, oxidative protein modification, and Aβ deposition in brain at early stages of pathology, but not at later stages, suggesting an early anti-inflammatory function of microglial EP4 signaling in the APP-PS1 model. Finally, EP4 receptor levels decreased significantly in human cortex with progression from normal to AD states, suggesting that early loss of this beneficial signaling system in preclinical AD development may contribute to subsequent progression of pathology. PMID:24760848

  14. [Receptors involved in the mechanism of action of topical prostaglandines].

    PubMed

    Neacsu, Alina Mihaela

    2009-01-01

    Hypotensive effect to prostaglandins analogs (latanoprost, travoprost, tafluprost) means to increase uveoscleral outflow by action to FP receptors who generated extracellular matrix changes and intermuscular spaces changes. Syntetic prostamides analogs (bimatoprost) have a particulary action with a receptors most and intensive studied. The bimatoprost effect is the consequences to preferated stimulations on the specific receptors who have action only the tissue with prostaglandins activity is important to specify what the bimatoprost have dual effect: to uveoscleral outflow and classic outflow by increase hidraulic conductivity.

  15. Rhizobacterial exopolysaccharides elicit induced resistance on cucumber.

    PubMed

    Park, Kyungseok; Kloepper, Joseph W; Ryu, Choong-Min

    2008-06-01

    The role of exopolysaccharides (EPSs) from a plant growth-promoting rhizobacterium, Burkholderia gladioli IN26, on elicitation of induced systemic resistance was investigated. A purified EPS induced expression of PR- 1a::GUS on tobacco and elicited induced resistance against Colletotrichum orbiculare on cucumber. The maximum level of disease protection was noted when seeds were soaked in 200 ppm of the EPS. Our results indicate that EPS from specific rhizobacteria can elicit induced resistance and suggest that bacterial EPS might be a useful elicitor of resistance under field conditions.

  16. Compartmentalization of prostaglandins in the canine kidney

    SciTech Connect

    Morgan-Boyd, R.L.

    1986-01-01

    The kidney has been shown to synthesize all of the naturally occurring major prostaglandins which may be restricted to a discrete part of the kidney where their actions are physiologically important, such as the vascular compartment and the tubular compartment. In order to examine this concept of compartmentalization, the authors conducted a series of experiments to determine whether PGl/sub 2/, measured as 6-keto-pGF/sub 1..cap alpha../, produced in the kidney is restricted to the renal vascular compartment or whether it also has access to the tubular compartment. Experiments were performed in the pentobarbital-anesthetized dog. Increasing pre-glomerular levels of 6-keto-PFG/sub 1..cap alpha../ caused marked increases in both the urinary excretion and the renal venous outflow to 6-keto-PGF/sub 1..cap alpha../. When /sup 3/H-6-keto-PGF/sub 1..cap alpha../ was co-infused with inulin into the renal artery, 33% of the radioactivity and 23% of the inulin was recovered on first pass. With infusion of /sup 3/H-PGl/sub 2/ and inulin, 20% of the radioactivity and 28% of the inulin reached the urine on first pass. Radioactive PGl/sub 2/ appeared to be less filterable at the glomeruli than either /sup 3/H-6-keto-PGF/sub 1..cap alpha../ or inulin. In the final set of experiments, in which dogs were prepared for a ureteral stopped-flow study, the PGE/sub 2//U/P/sub In/ ratio a peak was observed proximal to the Na/sup +/ plateau but distal to the Na+ nadir. In light of the results from the stopped-flow study and the intrarenal infusion studies, they conclude that PGE/sub 2/ synthesized in the kidney enters both the renal and tubular compartments. In contrast, they find that 6-keto-PGF/sub 1..cap alpha../ of renal origin enters only the renal origin enters only the renal vascular compartment and not the tubular compartment.

  17. [The antagonistic effect of aspirin on the expression of prostaglandin participation in the antihypertensive activity of ACE inhibitors].

    PubMed

    Alimento, M; Campodonico, J; Santambrogio, G; Rossi, M; Trabattoni, D; Celeste, F; Guazzi, M

    1997-06-01

    ACE-inhibitors antagonize both angiotensin production and bradykinin breakdown, resulting in enhancement of vasodilating prostaglandin release. This provides an explanation for the experimental observation that cycloxygenase blockers (such as aspirin or indomethacin) may counteract the antihypertensive efficacy of the ACE-inhibitors; it may be also possible that hypertensive patients taking aspirin as an antiplatelet agent may fail to benefit from ACE-inhibition. This study was aimed at: evaluating the magnitude and incidence of the inhibitory phenomenon; defining the minimal aspirin dosage that produces an antagonistic effect, as well as the possible reasons for a different individual susceptibility. We have studied untreated patients with mild (10 cases, Group 1), moderate (16 cases, Group 2) or severe (26 cases, Group 3) hypertension. The ACE-inhibitor enalapril was used at doses of 10 mg bid (groups 1 and 2) or 20 mg bid (Group 3). Active drug treatment periods had a 5-day duration. A daily dose of aspirin of 100 mg had no effect on the antihypertensive efficacy of enalapril. On the contrary, when a dose of 300 mg was used, 60, 57 and 50% of patients in Group 1, 2 and 3, respectively, showed a > 20% restraint of the mean arterial pressure fall with enalapril (20% was the lower arbitrary limit for defining antagonism). Inhibition was independent of the sequence of drug administration. In these patients counteraction averaged 60, 70 and 90%, respectively. In them, and not in the remaining patients in each group, aspirin substantially attenuated the renin rise elicited by ACE-inhibition. These data suggest that: a dosage of 100 mg aspirin is devoid of any inhibitory effect; more that 50% of ACE inhibited patients are, at least in the short term, susceptible to the action of 300 mg aspirin, regardless of the severity of hypertension; counteraction is seemingly mediated through a prostaglandin inhibition and depends on the individual predominance of prostaglandin

  18. Plasma prostaglandin E(2) metabolite levels during labor induction with a sustained-release prostaglandin E(2) vaginal insert.

    PubMed

    Goharkhay, N; Stanczyk, F Z; Gentzschein, E; Wing, D A

    2000-01-01

    To measure prostaglandin E(2) levels during labor induction with a sustained-release vaginal polymer insert (prostaglandin E(2) insert) and to determine whether Bishop score change correlated with tachysystole. Twelve primiparas and 12 multiparas were treated with a 0.3 mg per hour sustained-release polymer vaginal prostaglandin E(2) insert for up to 24 hours. Bishop score was assessed at start and end of therapy, and serum samples were collected at 4-hour intervals. Prostaglandin E(2) metabolite (PGEM) levels were measured by specific enzyme immunoassay. Exposure averaged 13.5 +/- 7.2 hours. Four patients (16.7%, three nulliparas) had tachysystole. Mean PGEM levels increased from 187 +/- 42 pg/mL at baseline to 548 +/- 110 pg/mL at 12 hours (P <.05) and remained relatively stable thereafter. Nulliparas with Bishop score changes of four points or more had the highest increase, with average peak levels of 985 +/- 109 pg/mL, compared with 452 +/- 58 pg/mL for all others (P <.001). Patients with tachysystole had higher 4-hour (P <.01) and overall (P <.04) increases in PGEM level. Removal of the insert led to an average decrease of 335 pg/mL in PGEM levels (P <.01). The decrease correlated with the PGEM level measured before removal (r =.94, P <.0001) and the maximum PGEM increase from baseline (r =.94, P <.0001). The mean mixed venous cord PGEM level was 409 +/- 375 pg/mL. Administration of the prostaglandin E(2) insert led to a sustained increase in circulating PGEM levels in women who had labor induction. Peak PGEM levels correlated with Bishop score improvement. Rapid increases in prostaglandin E(2) levels might cause tachysystole.

  19. A Knowledge Elicitation Study of Military Planning

    DTIC Science & Technology

    1990-02-01

    66027-0347 Ba. NAME OF FUNDING/SPONSORING 8b. OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER ORPANIZATION U.S. Army Research (If...Method (CDM) has been developed as a knowledge elicitation tool for probing proficient decision making. This report describes the use of CDM during...knowledge elicitation can be used in Army Command and Control (Ce) exercises as a means of understanding decision-making dynamics. Such a tool could

  20. Inhibition of Prostaglandin D Synthase Suppresses Muscular Necrosis

    PubMed Central

    Mohri, Ikuko; Aritake, Kosuke; Taniguchi, Hidetoshi; Sato, Yo; Kamauchi, Shinya; Nagata, Nanae; Maruyama, Toshihiko; Taniike, Masako; Urade, Yoshihiro

    2009-01-01

    Duchenne muscular dystrophy is a fatal muscle wasting disease that is characterized by a deficiency in the protein dystrophin. Previously, we reported that the expression of hematopoietic prostaglandin D synthase (HPGDS) appeared in necrotic muscle fibers from patients with either Duchenne muscular dystrophy or polymyositis. HPGDS is responsible for the production of the inflammatory mediator, prostaglandin D2. In this paper, we validated the hypothesis that HPGDS has a role in the etiology of muscular necrosis. We investigated the expression of HPGDS/ prostaglandin D2 signaling using two different mouse models of muscle necrosis, that is, bupivacaine-induced muscle necrosis and the mdx mouse, which has a genetic muscular dystrophy. We treated each mouse model with the HPGDS-specific inhibitor, HQL-79, and measured both necrotic muscle volume and selected cytokine mRNA levels. We confirmed that HPGDS expression was induced in necrotic muscle fibers in both bupivacaine-injected muscle and mdx mice. After administration of HQL-79, necrotic muscle volume was significantly decreased in both mouse models. Additionally, mRNA levels of both CD11b and transforming growth factor β1 were significantly lower in HQL-79-treated mdx mice than in vehicle-treated animals. We also demonstrated that HQL-79 suppressed prostaglandin D2 production and improved muscle strength in the mdx mouse. Our results show that HPGDS augments inflammation, which is followed by muscle injury. Furthermore, the inhibition of HPGDS ameliorates muscle necrosis even in cases of genetic muscular dystrophy. PMID:19359520

  1. The role of prostaglandins E1 and E2, dinoprostone, and misoprostol in cervical ripening and the induction of labor: a mechanistic approach.

    PubMed

    Bakker, Ronan; Pierce, Stephanie; Myers, Dean

    2017-08-01

    Prostaglandins play a critical role in cervical ripening by increasing inflammatory mediators in the cervix and inducing cervical remodeling. Prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2) exert different effects on these processes and on myometrial contractility. These mechanistic differences may affect outcomes in women treated with dinoprostone, a formulation identical to endogenous PGE2, compared with misoprostol, a PGE1 analog. The objective of this review is to evaluate existing evidence regarding mechanistic differences between PGE1 and PGE2, and consider the clinical implications of these differences in patients requiring cervical ripening for labor induction. We conducted a critical narrative review of peer-reviewed articles identified using PubMed and other online databases. While both dinoprostone and misoprostol are effective in cervical ripening and labor induction, they differ in their clinical and pharmacological profiles. PGE2 has been shown to stimulate interleukin-8, an inflammatory cytokine that promotes the influx of neutrophils and induces remodeling of the cervical extracellular matrix, and to induce functional progesterone withdrawal. Misoprostol has been shown to elicit a dose-dependent effect on myometrial contractility, which may affect rates of uterine tachysystole in clinical practice. Differences in the mechanism of action between misoprostol and PGE2 may contribute to their variable effects in the cervix and myometrium, and should be considered to optimize outcomes.

  2. [Prolonged pregnancy--prostaglandins as the cause of labor onset].

    PubMed

    Rath, W

    1994-01-01

    The causes of prolonged pregnancy are still largely unknown and their investigation requires a detailed observation of potential birth-initiating stimuli on the endocrine and biomolecular level. A large number of clinical and biochemical studies point to the central importance of prostaglandins for the beginning of human birth. The main places of origin of the intensified prostaglandin formation and release are the amnion and the decidua which has "macrophage-like" properties and functions. The superordinate regulation and trigger mechanisms for intensified uterine prostaglandin production has not been sufficiently investigated either. Possible factors currently being debated include local changes in estrogen and progesterone biosynthesis in fetal membranes and decidua, subclinical inflammatory reactions with the activation of macrophages and the consecutive release of cytokines, and a loss of maternal immune tolerance with a time-determined rejection reaction. In addition, the substances inhibiting and stimulating prostaglandin synthesis have been detected in the amniotic fluid, fetal membranes and decidua. The fetus itself also plays an important part in the initiation of labor. Prolongation may be due to anatomic functional disturbances of the one hand which prevent the activation of the fetal hypothalamic-hypophyseal-adrenal axis and the release of the birth-initiating stimuli originating in the fetus; on the other hand, an elevated immune tolerance with a delayed rejection reaction or the lack of "bacterial stimulus" may inhibit the activation of the macrophages and hence the formation of cytokines. The consequences would be the development and release of a quantity of prostaglandins from the fetal membranes and decidua insufficient to overcome the pregnancy-maintaining safety systems.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Long-term assessment of prostaglandin analogs and timolol fixed combinations vs prostaglandin analogs monotherapy

    PubMed Central

    Liu, Ai-Wei; Gan, Lin-Yang; Yao, Xiang; Zhou, Jian

    2016-01-01

    AIM To draw a Meta-analysis over the comparison of the intraocular pressure (IOP)-lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglandin analogs (PGAs) monotherapy. METHODS After searching the published reports from MEDLINE, EMBASE, the Cochrane Library, all randomized controlled clinical trials (RCTs) comparing the fixed combination of PGAs/timolol therapy (FCs) and PGAs monotherapy with treatment duration at least 6mo were included. The efficacy outcomes were mean diurnal IOP, percentage of participants whose IOP were lower than 18 mm Hg, incidence of visual field change, while the safety outcomes included corneal side effects, hyperemia and eye irritation. The analysis was carried out in RevMan version 5.3 software. RESULTS After six-month medical intervention, the mean diurnal IOP of FCs was lower than PGAs (MD -1.14, 95% CI -1.82 to -0.46, P=0.001); the percentage of target IOP achieving between FCs and PGAs showed no significant difference (RR 1.18, 95% CI 0.97 to 1.43, P=0.10). No statistically significant differences of the incidence of hyperemia (RR 0.67, 95% CI 0.45 to 1.01, P=0.06) and eye irritation (RR 1.20, 95% CI 0.95 to 1.51, P=0.12) between the FCs and PGAs monotherapy were detected. Only one research involved in corneal events, result of this trial revealed no difference between two intervention groups regarding corneal effects (central endothelial cell density, MD -0.20, 95% CI -0.72 to 0.32, P=0.45; central corneal thickness, MD -0.01, 95% CI -0.02 to 0.00, P=0.23). The evaluation of visual field change was not performed due to the limited duration of the trials included in this Meta-analysis. CONCLUSION The long-term efficacy of the FCs overweighed the PGAs monotherapy in lowering IOP, but in the incidence of hyperemia and eye irritation syndromes, the differences are not statically significant. More RCTs with detailed and authentic data over the assessments of

  4. [Problems of assessing the biological value of prostaglandin in vitro (author's transl)].

    PubMed

    Tullberg, K; Jacobi, H

    1978-01-01

    Isolated rat stomach strips were used to study the antagonism between psychotropic drugs and prostaglandin. It was found that the inhibited prostaglandin effect registered under the influence of psychotropic drugs in due not so much to the inhibition of synthetase action but rather to an inhibitory action on liberated prostaglandin. An atropine-like effect of the psychotropic drugs or an inhibition in the formation of endogenic prostaglandin in the walls are ruled out as possible explanations. The following possible explanations were discussed: a) the tested psychotropic drugs block prostaglandin receptors in the stomach; b) the test substances react with prostaglandin in the nutritive solution; c) the substances stimulate metabolic processes in the stomach wall that break down prostaglandin.

  5. Role of the prostaglandins in labour and prostaglandin receptor inhibitors in the prevention of preterm labour.

    PubMed

    Olson, David M; Ammann, Christina

    2007-01-01

    Parturition is composed of five separate but integrated physiological events: fetal membrane rupture, cervical dilatation, myometrial contractility, placental separation, and uterine involution. Prostaglandins (PGs) have central roles in each of these events, but the most studied is myometrial contraction. Elevated uterine PGs or the enhanced sensitivity of the myometrium to PGs leads to contractions and labour. The primary regulator of PG synthesis is the mRNA expression of PG H Synthase (PGHS-2 or COX-2). Given the central role of PGs in labour, this enzyme becomes an obvious therapeutic target for the prevention of preterm labour, the major cause of perinatal mortality and morbidity. Unfortunately, even though the non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit PGHS, are usually successful in suppressing preterm labour or prolonging pregnancy in animal and human studies, the NSAIDS have had adverse effects on fetal physiology and development. Therefore, other means to suppress PG synthesis or action to arrest preterm labour need to be investigated. The PGF2alpha receptor, FP, may prove to be a reasonable target for tocolysis. FP mRNA increases in the mouse uterus at preterm birth, whereas PGF2alpha concentrations do not increase, suggesting elevated uterine sensitivity to contractile agonists is one mechanism for preterm labour initiation. New data shows that administration of a specific FP antagonist, Theratechnologies (THG) 113.31, delays preterm birth in mice and sheep with no observable maternal or fetal side effects. Hence antagonizing PG action offers new hope for delaying preterm birth.

  6. Stereoscopy Amplifies Emotions Elicited by Facial Expressions

    PubMed Central

    Kätsyri, Jari; Häkkinen, Jukka

    2015-01-01

    Mediated facial expressions do not elicit emotions as strongly as real-life facial expressions, possibly due to the low fidelity of pictorial presentations in typical mediation technologies. In the present study, we investigated the extent to which stereoscopy amplifies emotions elicited by images of neutral, angry, and happy facial expressions. The emotional self-reports of positive and negative valence (which were evaluated separately) and arousal of 40 participants were recorded. The magnitude of perceived depth in the stereoscopic images was manipulated by varying the camera base at 15, 40, 65, 90, and 115 mm. The analyses controlled for participants’ gender, gender match, emotional empathy, and trait alexithymia. The results indicated that stereoscopy significantly amplified the negative valence and arousal elicited by angry expressions at the most natural (65 mm) camera base, whereas stereoscopy amplified the positive valence elicited by happy expressions in both the narrowed and most natural (15–65 mm) base conditions. Overall, the results indicate that stereoscopy amplifies the emotions elicited by mediated emotional facial expressions when the depth geometry is close to natural. The findings highlight the sensitivity of the visual system to depth and its effect on emotions. PMID:27551358

  7. Stereoscopy Amplifies Emotions Elicited by Facial Expressions.

    PubMed

    Hakala, Jussi; Kätsyri, Jari; Häkkinen, Jukka

    2015-12-01

    Mediated facial expressions do not elicit emotions as strongly as real-life facial expressions, possibly due to the low fidelity of pictorial presentations in typical mediation technologies. In the present study, we investigated the extent to which stereoscopy amplifies emotions elicited by images of neutral, angry, and happy facial expressions. The emotional self-reports of positive and negative valence (which were evaluated separately) and arousal of 40 participants were recorded. The magnitude of perceived depth in the stereoscopic images was manipulated by varying the camera base at 15, 40, 65, 90, and 115 mm. The analyses controlled for participants' gender, gender match, emotional empathy, and trait alexithymia. The results indicated that stereoscopy significantly amplified the negative valence and arousal elicited by angry expressions at the most natural (65 mm) camera base, whereas stereoscopy amplified the positive valence elicited by happy expressions in both the narrowed and most natural (15-65 mm) base conditions. Overall, the results indicate that stereoscopy amplifies the emotions elicited by mediated emotional facial expressions when the depth geometry is close to natural. The findings highlight the sensitivity of the visual system to depth and its effect on emotions.

  8. Function of prostaglandin E2 EP receptors in the acute outcome of rodent hypoxic ischemic encephalopathy

    PubMed Central

    Taniguchi, Hidetoshi; Anacker, Christoph; Suarez-Mier, Gabriela Beatriz; Wang, Qian; Andreasson, Katrin

    2011-01-01

    Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of severe and permanent neurologic disability after birth. The inducible cyclooxygenase COX-2, which along with COX-1 catalyzes the first committed step in prostaglandin (PG) synthesis, elicits significant brain injury in models of cerebral ischemia, however its downstream PG receptor pathways trigger both toxic and paradoxically protective effects. Here, we investigated the function of PGE2 E-prostanoid (EP) receptors in the acute outcome of hypoxic-ischemic (HI) injury in the neonatal rat. We determined the temporal and cellular expression patterns of the EP1-4 receptors before and after HIE and tested whether modulation of EP1-4 receptor function could protect against cerebral injury acutely after HIE. All four EP receptors were expressed in forebrain neurons and were induced in endothelial cells after HIE. Inhibition of EP1 signaling with the selective antagonist SC-51089 or co-activation of EP2-4 receptors with the agonist misoprostol significantly reduced HIE cerebral injury 24h after injury. These receptor ligands also protected brain endothelial cells subjected to oxygen glucose deprivation, suggesting that activation of EP receptor signaling is directly cytoprotective. These data indicate that the G-protein coupled EP receptors may be amenable to pharmacologic targeting in the acute setting of neonatal HIE. PMID:21939736

  9. Niacin ameliorates ulcerative colitis via prostaglandin D2-mediated D prostanoid receptor 1 activation.

    PubMed

    Li, Juanjuan; Kong, Deping; Wang, Qi; Wu, Wei; Tang, Yanping; Bai, Tingting; Guo, Liang; Wei, Lumin; Zhang, Qianqian; Yu, Yu; Qian, Yuting; Zuo, Shengkai; Liu, Guizhu; Liu, Qian; Wu, Sheng; Zang, Yi; Zhu, Qian; Jia, Daile; Wang, Yuanyang; Yao, Weiyan; Ji, Yong; Yin, Huiyong; Nakamura, Masataka; Lazarus, Michael; Breyer, Richard M; Wang, Lifu; Yu, Ying

    2017-03-24

    Niacin, as an antidyslipidemic drug, elicits a strong flushing response by release of prostaglandin (PG) D2 However, whether niacin is beneficial for inflammatory bowel disease (IBD) remains unclear. Here, we observed niacin administration-enhanced PGD2 production in colon tissues in dextran sulfate sodium (DSS)-challenged mice, and protected mice against DSS or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in D prostanoid receptor 1 (DP1)-dependent manner. Specific ablation of DP1 receptor in vascular endothelial cells, colonic epithelium, and myeloid cells augmented DSS/TNBS-induced colitis in mice through increasing vascular permeability, promoting apoptosis of epithelial cells, and stimulating pro-inflammatory cytokine secretion of macrophages, respectively. Niacin treatment improved vascular permeability, reduced apoptotic epithelial cells, promoted epithelial cell update, and suppressed pro-inflammatory gene expression of macrophages. Moreover, treatment with niacin-containing retention enema effectively promoted UC clinical remission and mucosal healing in patients with moderately active disease. Therefore, niacin displayed multiple beneficial effects on DSS/TNBS-induced colitis in mice by activation of PGD2/DP1 axis. The potential efficacy of niacin in management of IBD warrants further investigation.

  10. Prostaglandin I2 enhances cough reflex sensitivity to capsaicin in the asthmatic airway

    PubMed Central

    Ishiura, Yoshihisa; Fujimura, Masaki; Nobata, Kouichi; Oribe, Yoshitaka; Abo, Miki; Myou, Shigeharu

    2007-01-01

    Inflammatory mediators are involved in the pathogenesis of airway inflammation, but the role of prostaglandin I2 (PGI2) remains obscure. This study was designed to investigate the role of PGI2 in cough reflex sensitivity of the asthmatic airway, which is characterized by chronic eosinophilic airway inflammation. The effect of beraprost, a chemically and biologically stable analogue of PGI2, on cough response to inhaled capsaicin was examined in 21 patients with stable asthma in a randomized, placebo-controlled cross over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. The cough threshold was significantly (p < 0.05) decreased after two weeks of treatment with beraprost [17.8 (GSEM 1.20) μM] compared with placebo [30.3 (GSEM 1.21) μM]. PGI2 increases cough reflex sensitivity of the asthmatic airway, suggesting that inhibition of PGI2 may be a novel therapeutic option for patients with asthma, especially cough predominant asthma. PMID:17222337

  11. Rational elicitation of cold-sensitive phenotypes

    PubMed Central

    Baliga, Chetana; Majhi, Sandipan; Mondal, Kajari; Bhattacharjee, Antara; Varadarajan, Raghavan

    2016-01-01

    Cold-sensitive phenotypes have helped us understand macromolecular assembly and biological phenomena, yet few attempts have been made to understand the basis of cold sensitivity or to elicit it by design. We report a method for rational design of cold-sensitive phenotypes. The method involves generation of partial loss-of-function mutants, at either buried or functional sites, coupled with selective overexpression strategies. The only essential input is amino acid sequence, although available structural information can be used as well. The method has been used to elicit cold-sensitive mutants of a variety of proteins, both monomeric and dimeric, and in multiple organisms, namely Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster. This simple, yet effective technique of inducing cold sensitivity eliminates the need for complex mutations and provides a plausible molecular mechanism for eliciting cold-sensitive phenotypes. PMID:27091994

  12. Films for eliciting emotional states in children.

    PubMed

    von Leupoldt, Andreas; Rohde, Jenny; Beregova, Anna; Thordsen-Sörensen, Imke; zur Nieden, Janine; Dahme, Bernhard

    2007-08-01

    Standardized sets of films have been shown to be effective for eliciting emotional states in adults, but no comparable validated stimuli are available for children. We therefore examined the effects of three pre-selected film clips each of 3-min duration in eliciting a pleasant, neutral and unpleasant emotional state in 297 children aged between 6 and 12 years. After the films were presented on a video projector, affective ratings were obtained with the Self-Assessment-Manikin on the emotional dimensions of valence and arousal. Increasing pleasure ratings were observed from the unpleasant to the neutral to the pleasant film. Associated arousal ratings were stronger for the unpleasant and pleasant films compared to the neutral film. Overall, results showed successful elicitation of targeted emotional states only marginally influenced by age, gender or prior experience with the films. The use of these films is therefore suggested for future studies on emotions in children.

  13. Effects of centrally administered prostaglandin E(3) and thromboxane A(3) on plasma noradrenaline and adrenaline in rats: comparison with prostaglandin E(2) and thromboxane A(2).

    PubMed

    Shimizu, Takahiro; Yokotani, Kunihiko

    2009-06-02

    Previously, we reported the involvement of brain omega-6 prostanoids, especially prostaglandin E(2) and thromboxane A(2), in the activation of central sympatho-adrenomedullary outflow in rats. omega-3 Prostanoids, including prostaglandin E(3) and thromboxane A(3), are believed to be less bioactive than omega-6 prostanoids, although studies on the functions of omega-3 prostanoids in the central nervous system have not been reported. In the present study, therefore, we compared the effects of centrally administered omega-3 prostanoids, prostaglandin E(3) and thromboxane A(3), with those of omega-6 prostanoids, prostaglandin E(2) and thromboxane A(2), on the plasma catecholamines in anesthetized rats. Intracerebroventricularly (i.c.v.) administered prostaglandin E(2) (0.15, 0.3 and 1.5 nmol/animal) and prostaglandin E(3) (0.3 and 3 nmol/animal) predominantly elevated plasma noradrenaline but not adrenaline, but the latter was less efficient than the former. On the other hand, U-46619 (an analog of thromboxane A(2)) (30, 100 and 300 nmol/animal, i.c.v.) and Delta(17)-U-46619 (an analog of thromboxane A(3)) (100 and 300 nmol/animal, i.c.v.) both elevated plasma catecholamines (adrenaline>noradrenaline) to the same degree. These results suggest that centrally administered prostaglandin E(3) is less effective than prostaglandin E(2) to elevate plasma noradrenaline, and that thromboxane A(3) is almost as equipotent as thromboxane A(2) to elevate plasma catecholamines in rats.

  14. Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta-oxidation is a major importance for in vivo degradation of prostaglandins in humans.

    PubMed Central

    Diczfalusy, U; Kase, B F; Alexson, S E; Björkhem, I

    1991-01-01

    We have recently shown in vitro that the peroxisomal fraction of a rat liver homogenate has the highest capacity to beta-oxidize prostaglandins. In order to evaluate the relative importance of peroxisomes for this conversion also in vivo, we administered [3H]prostaglandin F2 alpha to an infant suffering from Zellweger syndrome, a congenital disorder characterized by the absence of intact peroxisomes. As a control, labeled compound was administered to two healthy volunteers. Urine was collected, fractionated on a SEP-PAK C18 cartridge, and subjected to reversed-phase high-performance liquid chromatography. The Zellweger patient was found to excrete prostaglandin metabolites considerably less polar than those of the control subjects. The major urinary metabolite in the control subjects was practically absent in the urine from the Zellweger patient. The major urinary prostaglandin F2 alpha metabolite from the Zellweger patient was identified as an omega-oxidized C20-prostaglandin, 9,11-dihydroxy-15-oxoprost-5-ene-1,20-dioic acid. The major urinary prostaglandin F2 alpha metabolite from the control subjects had chromatographic properties of a tetranor (C16) prostaglandin, in accordance with earlier published data. The present results, in combination with our previous in vitro data, indicate that peroxisomal beta-oxidation is of major importance for in vivo chain shortening of prostaglandins. PMID:1885782

  15. Induction of labor using prostaglandin vaginal gel: cost analysis comparing early amniotomy with repeat prostaglandin gel.

    PubMed

    Beckmann, Michael; Merollini, Katharina; Kumar, Sailesh; Flenady, Vicki

    2016-04-01

    In a randomized controlled trial of two policies for induction of labor (IOL) using Prostaglandin E2 (PGE2) vaginal gel, women who had an earlier amniotomy experienced a shorter IOL-to-birth time. To report the cost analysis of this trial and determine if there are differences in healthcare costs when an early amniotomy is performed as opposed to giving more PGE2 vaginal gel, for women undergoing IOL at term. Following an evening dose of PGE2 vaginal gel, 245 women with live singleton pregnancies, ≥37+0 weeks, were randomized into an amniotomy or repeat-PGE2 group. Healthcare costs were a secondary outcome measure, sourced from hospital finance systems and included staff costs, equipment and consumables, pharmacy, pathology, hotel services and business overheads. A decision analytic model, specifically a Markov chain, was developed to further investigate costs, and a Monte Carlo simulation was performed to confirm the robustness of these findings. Mean and median costs and cost differences between the two groups are reported, from the hospital perspective. The healthcare costs associated with IOL were available for all 245 trial participants. A 1000-patient cohort simulation demonstrated that performing an early amniotomy was associated with a cost-saving of $AUD289 ($AUD7094 vs $AUD7338) per woman induced, compared with administering more PGE2. Propagating the uncertainty through the model 10,000 times, early amniotomy was associated with a median cost savings of $AUD487 (IQR -$AUD573, +$AUD1498). After an initial dose of PGE2 vaginal gel, a policy of administering more PGE2 when the Modified Bishop's score is <7 was associated with increased healthcare costs compared with a policy of performing an amniotomy, if technically possible. Length of stay was the main driver of healthcare costs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. [Prostaglandin E2 gel for labor induction in preterm pregnancy].

    PubMed

    Sieńko, Jacek; Czajkowski, Krzysztof; Nowak, Rafał; Broś, Magdalena; Kunicki, Michał; Strzyzewski, Wojciech

    2003-01-01

    Endocervical prostaglandin E2 gel administration is widely accepted mean of induction of labor in pregnancy at term. Further investigation is needed to assess its usage in pregnancy below 37 weeks' gestation. The aim of this study is to analyse the course of labor, its complications and neonatal outcome in preterm deliveries induced with endocervical dinoprostone. We conducted a retrospective study of 22 preterm deliveries induced with dinoprostone. A control group consisted of 26 pregnancies at term. The incidence of cesarean sections was comparable in both preterm and term deliveries (45 vs. 41%, p = 0.38). We found no differences in characteristics of indications of operative delivery, duration of particular stages of labor; time from dinoprostone administration to the beginning of 1st stage of labor, estimated blood loss. 1 and 5-minute Apgar scores were similar in both groups. Endocervical prostaglandin E2 gel administration seems to be a safe method of induction of labor in preterm pregnancy.

  17. Prostaglandin E receptors as inflammatory therapeutic targets for atherosclerosis.

    PubMed

    Yang, Cui; Liu, Xiuxia; Cao, Qing; Liang, Qian; Qiu, Xiaohua

    2011-01-31

    Prostaglandin E receptors (EPs) are the G-protein-coupled receptors (GPCRs) that respond to type E(2) prostaglandin (PGE(2)). Data has shown that PGE(2) may function as an endogenous anti-inflammatory mediator by suppressing the production of cytokines. However, other studies have demonstrated that PGE(2), a pro-inflammatory mediator produced by various cell types within the wounded vascular wall, plays a crucial role in early atherosclerotic development. These contradictory results may be due to the versatility of EPs. Experimental data suggest an individual role for each PGE(2) receptor, such as EP(1), EP(2), EP(3) and EP(4), in atherosclerosis. In this review, the roles of EPs in atherosclerosis are summarized, and the value of EPs as new therapeutic targets for atherosclerosis is explored.

  18. The harlequin color change and association with prostaglandin E1.

    PubMed

    Rao, Jaggi; Campbell, Morag E; Krol, Alfons

    2004-01-01

    The harlequin color change is an unusual cutaneous phenomenon observed in newborn infants as transient, benign episodes of a sharply demarcated erythema on half of the infant, with simultaneous contralateral blanching. In this report, two newborns with congenital heart anomalies demonstrated the harlequin color change, one whose skin findings showed a course related to the dose of systemic prostaglandin E1, suggesting a possible association. The benign, self-limited nature of the color change mandates that prostaglandin E1 not be discontinued for this reason. The entity is likely more common than the paucity of reports in the world literature suggests, and all physicians should recognize its graphic appearance to avoid unnecessary exposure to agents in an effort to treat it.

  19. Initial Treatment: Prostaglandin Analog or Selective Laser Trabeculoplasty.

    PubMed

    Clement, Colin I

    2012-01-01

    Prostaglandin analogs (PGA) have been the initial treatment of choice in many patients with glaucoma. However, there is an increasing awareness that non adherence and disruption of the ocular surface may limit PGA utility and tolerability respectively in some patients. In an eye with an open iridocorneal angle, these issues can potentially be addressed with the use of laser trabeculoplasty (LT). This therapy can achieve long-term intraocular pressure reduction following 1 to 2 treatment sessions without the ongoing need to apply medication (and preservatives) to the ocular surface. Whether PGAs or LT should be used in a given individual will also be influenced by other important factors including efficacy, response rate, tolerability, complications, cost and accessibility. This review examines these issues in relation to the initiation of primary therapy. How to cite this article: Clement CI. Initial Treatment: Prostaglandin Analog of Selective Laser Trabeculoplasty. J Current Glau Prac 2012;6(3):99-103.

  20. Sex, drugs and sports: prostaglandins, epitestosterone and sexual development.

    PubMed

    Sanders, Bryan K

    2007-01-01

    Amateau and McCarthy's findings published in Nature Neuroscience (June 2004) are noteworthy for suggesting a role for prostaglandins in sexual development. However, evidence suggests that in manipulating PGE2, they unknowingly implicated 3alpha-hydroxysteroid dehydrogenase [E.C. 1.1.1.50], 3(or 17)alpha-hydroxysteroid dehydrogenase [E.C. 1.1.1.209] and their respective products, androsterone (ADT) and epitestosterone (EpiT), in the developmental masculinization of sex behavior. EpiT is generally regarded as a hormonally inactive 17alpha-epimer of testosterone (T). In rats, the kidney is the primary site of EpiT formation, whereas in humans it originates from the gonads, with only a small contribution secreted by the adrenals. Because the ratio of T to EpiT is nearly constant, it is presently used for assessing steroid abuse in competitive sports, where the World Anti-Doping Agency (WADA) considers a T/EpiT ratio >4 evidence of T doping. Despite its central role in the detection of illict anabolic steroid use, our knowledge of factors effecting EpiT production is poor. Clues in the literature, however, reveal that prostaglandin-mediated processes, such as LHRH release, may influence its production. Antimycotics, NSAIDs, and opioid analgesics used in sports medicine are all known to effect prostaglandin E2 synthesis. Primary PGs are potent inhibitors of ADT oxidation, while indomethacin, a prostaglandin blocker, powerfully inhibits 3alpha-HSD reduction and ADT oxidation. This is significant because ADT inhibits the oxidation of EpiT, and may modulate its antiandrogenic and neuroprotective effects. It is hypothesized that the T/EpiT ratio is increased by COX-2 inhibitors and opiod analgesics, and decreased by antimycotics that do not impair testosterone biosynthesis. Given the devastating personal and career consequences that may result from false positive drug tests, substantive research on the effects of PGE2 manipulations on EpiT is warranted.

  1. Prostaglandin concentrations in the semen of fertile men.

    PubMed

    Templeton, A A; Cooper, I; Kelly, R W

    1978-01-01

    The PG concentrations in the semen of 23 fertile men were 73 microgram PGE/ml, 267 microgram 19-OH PGE/ml, 2.1 microgram PGF/ml and 18.3 microgram 19-OH PGF/ml. The wide ranges of concentrations found for the PGEs (2-272 microgram/ml) and for the 19-OH PGEs (53-1094 microgram/ml) throw some doubt on the previously established correlation between infertility and low prostaglandin concentrations.

  2. Realistic Real World Contexts: Model Eliciting Activities

    ERIC Educational Resources Information Center

    Doruk, Bekir Kürsat

    2016-01-01

    Researchers have proposed a variety of methods to make a connection between real life and mathematics so that it can be learned in a practical way and enable people to utilise mathematics in their daily lives. Model-eliciting activities (MEAs) were developed to fulfil this need and are very capable of serving this purpose. The reason MEAs are so…

  3. Video Elicitation of the Semiotic Self.

    ERIC Educational Resources Information Center

    Stockall, Nancy

    2001-01-01

    Illustrates the power of video recording to elicit the thinking of teachers as they reflect on their teaching practices. Draws on the work of Wiley (1994), which identified the internal conversation as a critical feature of the semiotic self. (Author/VWL)

  4. Eliciting User Requirements Using Appreciative Inquiry

    ERIC Educational Resources Information Center

    Gonzales, Carol Kernitzki

    2010-01-01

    Many software development projects fail because they do not meet the needs of users, are over-budget, and abandoned. To address this problem, the user requirements elicitation process was modified based on principles of Appreciative Inquiry. Appreciative Inquiry, commonly used in organizational development, aims to build organizations, processes,…

  5. Methods of Eliciting Information from Experts

    DTIC Science & Technology

    1987-10-01

    Itzhak Perlman) or a concertmeister in an orchestra, or simply one of its violinists . Differences in amount of expertise may supply different...would lead to becoming a world class violinist . Underlying Assumptions In attempting to elicit information from experts, one makes a number of

  6. Eliciting User Requirements Using Appreciative Inquiry

    ERIC Educational Resources Information Center

    Gonzales, Carol Kernitzki

    2010-01-01

    Many software development projects fail because they do not meet the needs of users, are over-budget, and abandoned. To address this problem, the user requirements elicitation process was modified based on principles of Appreciative Inquiry. Appreciative Inquiry, commonly used in organizational development, aims to build organizations, processes,…

  7. Realistic Real World Contexts: Model Eliciting Activities

    ERIC Educational Resources Information Center

    Doruk, Bekir Kürsat

    2016-01-01

    Researchers have proposed a variety of methods to make a connection between real life and mathematics so that it can be learned in a practical way and enable people to utilise mathematics in their daily lives. Model-eliciting activities (MEAs) were developed to fulfil this need and are very capable of serving this purpose. The reason MEAs are so…

  8. Effects of nonhypotensive endotoxemia in conscious rats: Role of prostaglandins

    SciTech Connect

    Burnier, M.; Waeber, B.; Aubert, J.F.; Nussberger, J.; Brunner, H.R. )

    1988-03-01

    A nonhypotensive dose of endotoxin was administered to normal conscious rats to evaluate the vascular and humoral effects of endotoxemia per se. Mean blood pressure and heart rate remained stable during the 45 min infusion of Escherichia coli endotoxin. However, a marked increase in plasma renin activity plasma epinephrine and plasma norepinephrine was observed during infusion in endotoxin-treated rats when compared with the vehicle-treated animals. In addition, the blood pressure response to exogenous norepinephrine was significantly reduced during nonhypotensive endotoxemia. Significant changes in regional blood flow distribution, as assessed by radiolabeled microspheres, were observed in endotoxemic rats; in particular a decrease in renal blood flow, and an increase in coronary blood flow were found. The role of prostaglandins in the vascular and humoral alterations induced by nonhypotensive endotoxemia was also examined. Pretreatment with indomethacin (5 mg) prevent the increase in plasma renin activity as well as plasma catecholamine levels. On the contrary, the decreased vascular reactivity and the reduction in renal blood flow observed during endotoxemia were not affected by prostaglandin synthesis inhibition. Thus significant vascular and humoral changes have been found during endotoxemia even in absence of hypotension. The humoral but not the vascular effects of endotoxemia were abolished when prostaglandin synthesis was inhibited.

  9. Mid trimester abortion by one shot administration of prostaglandin.

    PubMed

    Ganguli, A C; Krishna, U R; Mhatre, V S; Purandare, V N

    1977-10-01

    268 cases in which mid trimester abortion in the 2nd trimester of pregnancy was performed by injecting prostaglandins by intra-amniotic route were studied. Details are presented of 1 study in which 100 cases had prostaglandin injected intraamniotically in 1 shot. 50 cases received 50 mg of PGF2a and 40 received 2.5 mg of 15 Methyl PGF2a, an analogue more potent and longer acting. The majority of the patients were primigravida, most of these being unmarried mothers. The average gestation period in both groups was between 17-18 weeks. The average induction onset interval was considerably shorter in PGF2a group, but its abortion time was just about 1 hour less than that of the methyl analogue. The average incidence of vomiting is about 2-folds and that of loose motionsis almost 5 times in the 15 Methyl group. 81% of the patients were followed up, and 86% of this group stopped bleeding within 10 days and the remaining within 20 days. There has not been a single incidence of post abortal infection. The disadvantages associated with the original intravenous administration of prostaglandin have been overcome by using the intra-amniotic routes. 1 of the greatest advantages of 1 shot intra-amniotic PGF2a 50 mg was a low incidence of incomplete abortion. Only 12% of cases in this group had retained placenta compared to 40-50% in the other groups.

  10. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis

    PubMed Central

    North, Trista E.; Goessling, Wolfram; Walkley, Carl R.; Lengerke, Claudia; Kopani, Kamden R.; Lord, Allegra M.; Weber, Gerhard J.; Bowman, Teresa V.; Jang, Il-Ho; Grosser, Tilo; FitzGerald, Garret A.; Daley, George Q.; Orkin, Stuart H.; Zon, Leonard I.

    2009-01-01

    Haematopoietic stem cell (HSC) homeostasis is tightly controlled by growth factors, signalling molecules and transcription factors. Definitive HSCs derived during embryogenesis in the aorta-gonad-mesonephros region subsequently colonize fetal and adult haematopoietic organs1,2. To identify new modulators of HSC formation and homeostasis, a panel of biologically active compounds was screened for effects on stem cell induction in the zebrafish aorta-gonad-mesonephros region. Here, we show that chemicals that enhance prostaglandin (PG) E2 synthesis increased HSC numbers, and those that block prostaglandin synthesis decreased stem cell numbers. The cyclooxygenases responsible for PGE2 synthesis were required for HSC formation. A stable derivative of PGE2 improved kidney marrow recovery following irradiation injury in the adult zebrafish. In murine embryonic stem cell differentiation assays, PGE2 caused amplification of multipotent progenitors. Furthermore, ex vivo exposure to stabilized PGE2 enhanced spleen colony forming units at day 12 post transplant and increased the frequency of long-term repopulating HSCs present in murine bone marrow after limiting dilution competitive transplantation. The conserved role for PGE2 in the regulation of vertebrate HSC homeostasis indicates that modulation of the prostaglandin pathway may facilitate expansion of HSC number for therapeutic purposes. PMID:17581586

  11. Mechanism and clinical significance of prostaglandin-induced iris pigmentation.

    PubMed

    Stjernschantz, Johan W; Albert, Daniel M; Hu, Dan-Ning; Drago, Filippo; Wistrand, Per J

    2002-08-01

    The new glaucoma drugs latanoprost, isopropyl unoprostone, travoprost, and bimatoprost cause increased pigmentation of the iris in some patients. The purpose of the present article is to survey the available preclinical and clinical data on prostaglandin-induced iris pigmentation and to assess the phenomenon from a clinical perspective. Most of the data have been obtained with latanoprost, and it appears that there is a predisposition to latanoprost-induced iris pigmentation in individuals with hazel or heterochromic eye color. As latanoprost and travoprost are selective agonists for the prostaglandin F(2alpha) receptor, it is likely that the phenomenon is mediated by this receptor. Several studies indicate that latanoprost stimulates melanogenesis in iridial melanocytes, and transcription of the tyrosinase gene is upregulated. The safety aspects of latanoprost-induced iris pigmentation have been addressed in histopathologic studies, and no evidence of harmful consequences of the side effect has been found. Although a final assessment of the clinical significance of prostaglandin-induced iris pigmentation currently is impossible to make, it appears that the only clear-cut disadvantage is a potential heterochromia between the eyes in unilaterally treated patients because the heterochromia is likely to be permanent, or very slowly reversible.

  12. [Prostaglandin inhibitor indomethacin inhibits afferent activities of Adelta and C units in the saphenous nerve of diabetic hyperalgesic rats].

    PubMed

    Liu, Jian; Zhang, Qiao-Jun; Guo, Bei-Chuan; Cao, Dong-Yuan; Wang, Ke-Mo

    2002-10-25

    The effects of a non-selective inhibitor of cyclo-oxygenase (COX) indomethacin, and exogenous prostaglandin E(2) (PGE(2)) on A(delta) units and C units in the saphenous nerve of diabetic hyperalgesic rats were studied. The results showed that the conduction velocity of A(delta) units and C units and their mechanical threshold in diabetic hyperalgesic rats were obviously decreased, and a small number of A(delta) units (4/24) and C units (2/18) produced increased spontaneous activities. Intraperitoneal injection of indomethacin in diabetic hyperalgesic rats significantly relieved mechanical hyperalgesia, and resulted in a decrease in spontaneous afferent activities of the A(delta) units and C units. Subcutaneous injection of exogenous PGE(2) into the diabetic hyperalgesic and control rats produced a significant decrease in mechanical threshold of the A(delta) units and C units, and elicited discharge from 3 A(delta) units (3/24) and 1 C unit (1/18) in diabetic hyperalgesic rats and from 2 A(delta) units (2/13) in control rats. The present data suggest that the synthesis and release of PGs are increased in diabetic neuropathy, PGs can sensitize and /or activate A(delta) units and C units and elicit hyperalgesia and allodynia in diabetic rats.

  13. Blockade of prostaglandin E2-induced thermogenesis by unilateral microinjection of GABAA receptor antagonist into the preoptic area.

    PubMed

    Osaka, Toshimasa

    2008-09-16

    Previous studies have demonstrated that pretreatment of rats with a GABA(A) receptor antagonist microinjected bilaterally into the preoptic area (POA) blocked cold- or lipopolysaccharide-induced thermogenesis. Here, the involvement of GABA(A) receptors in prostaglandin (PG)E2-induced fever was examined. Thermogenic, tachycardic, vasoconstrictive, and hyperthermic responses were elicited by the unilateral microinjection of 0.57-1.1 pmol PGE2 into the region adjacent to the organum vasculosum of the lamina terminalis in urethane-chloralose-anesthetized rats. All these responses were blocked 10 min after pretreatment of the rats with a GABA(A) receptor antagonist, bicuculline methiodide or gabazine (50-500 pmol), microinjected unilaterally into the POA; and recovery occurred at approximately 70 min. Though the antagonist treatment alone had no effect on the O2 consumption rate or colonic temperature, it did elicit a bradycardic response. Pretreatment with the vehicle, saline, had no effect on the PGE2-induced responses. However, the blocking action of bicuculline/gabazine was efficacious when the agent was administered unilaterally, but not necessarily bilaterally, into the POA either contralateral or ipsilateral to the PGE2 injection site. These results suggest that the PGE2-induced responses are not simply mediated by the GABAergic transmission from the PGE2-sensitive site to the thermoefferent structure in the POA, although a tonic inhibitory input to POA neurons has a permissive role for the full expression of PGE2-induced fever.

  14. Mechanical stimulation of skeletal muscle cells mitigates glucocorticoid-induced decreases in prostaglandin production and prostaglandin synthase activity

    NASA Technical Reports Server (NTRS)

    Chromiak, J. A.; Vandenburgh, H. H.

    1994-01-01

    The glucocorticoid dexamethasone (Dex) induces a decline in protein synthesis and protein content in tissue cultured, avian skeletal muscle cells, and this atrophy is attenuated by repetitive mechanical stretch. Since the prostaglandin synthesis inhibitor indomethacin mitigated this stretch attenuation of muscle atrophy, the effects of Dex and mechanical stretch on prostaglandin production and prostaglandin H synthase (PGHS) activity were examined. In static cultures, 10(-8) M Dex reduced PGF2 alpha production 55-65% and PGE2 production 84-90% after 24-72 h of incubation. Repetitive 10% stretch-relaxations of non-Dex-treated cultures increased PGF2 alpha efflux 41% at 24 h and 276% at 72 h, and increased PGE2 production 51% at 24 h and 236% at 72 h. Mechanical stimulation of Dex-treated cultures increased PGF2 alpha production 162% after 24 h, returning PGF2 alpha efflux to the level of non-Dex-treated cultures. At 72 h, stretch increased PGF2 alpha efflux 65% in Dex-treated cultures. Mechanical stimulation of Dex-treated cultures also increased PGE2 production at 24 h, but not at 72 h. Dex reduced PGHS activity in the muscle cultures by 70% after 8-24 h of incubation, and mechanical stimulation of the Dex-treated cultures increased PGHS activity by 98% after 24 h. Repetitive mechanical stimulation attenuates the catabolic effects of Dex on cultured skeletal muscle cells in part by mitigating the Dex-induced declines in PGHS activity and prostaglandin production.

  15. Mechanical stimulation of skeletal muscle cells mitigates glucocorticoid-induced decreases in prostaglandin production and prostaglandin synthase activity

    NASA Technical Reports Server (NTRS)

    Chromiak, J. A.; Vandenburgh, H. H.

    1994-01-01

    The glucocorticoid dexamethasone (Dex) induces a decline in protein synthesis and protein content in tissue cultured, avian skeletal muscle cells, and this atrophy is attenuated by repetitive mechanical stretch. Since the prostaglandin synthesis inhibitor indomethacin mitigated this stretch attenuation of muscle atrophy, the effects of Dex and mechanical stretch on prostaglandin production and prostaglandin H synthase (PGHS) activity were examined. In static cultures, 10(-8) M Dex reduced PGF2 alpha production 55-65% and PGE2 production 84-90% after 24-72 h of incubation. Repetitive 10% stretch-relaxations of non-Dex-treated cultures increased PGF2 alpha efflux 41% at 24 h and 276% at 72 h, and increased PGE2 production 51% at 24 h and 236% at 72 h. Mechanical stimulation of Dex-treated cultures increased PGF2 alpha production 162% after 24 h, returning PGF2 alpha efflux to the level of non-Dex-treated cultures. At 72 h, stretch increased PGF2 alpha efflux 65% in Dex-treated cultures. Mechanical stimulation of Dex-treated cultures also increased PGE2 production at 24 h, but not at 72 h. Dex reduced PGHS activity in the muscle cultures by 70% after 8-24 h of incubation, and mechanical stimulation of the Dex-treated cultures increased PGHS activity by 98% after 24 h. Repetitive mechanical stimulation attenuates the catabolic effects of Dex on cultured skeletal muscle cells in part by mitigating the Dex-induced declines in PGHS activity and prostaglandin production.

  16. Role of endogenous prostaglandins in protection of rat gastric mucosa by tripotassium dicitrate bismuthate.

    PubMed

    Malandrino, S; Bestetti, A; Fumagalli, G; Borsa, M; Viganó, T; Tonon, G

    1987-10-01

    Gross and microscopic examination of rat gastric mucosa demonstrated that intragastric administration to rats of tripotassium dicitrate bismuthate (TDB), a colloidal bismuth compound, protects against gastric lesions induced by 85% ethanol. Indomethacin, a prostaglandin synthetase inhibitor, significantly blocked the gastric mucosal protective effect of TDB. The release of gastric mucosal prostaglandins was greater in animals treated with TDB than in control animals, both time- and dose-dependently. These results seem to indicate involvement of prostaglandins in the action of TDB.

  17. Preeclampsia -- a state of prostaglandin deficiency? Urinary prostaglandin excretion, the renin-aldosterone system, and circulating catecholamines in preeclampsia.

    PubMed

    Pedersen, E B; Christensen, N J; Christensen, P; Johannesen, P; Kornerup, H J; Kristensen, S; Lauritsen, J G; Leyssac, P P; Rasmussen, A; Wohlert, M

    1983-01-01

    Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin, aldosterone, norepinephrine (NE) and epinephrine (E) were determined during pregnancy, 5 days, 3, and 6 months after delivery in preeclampsia, normotensive pregnant, and nonpregnant control subjects. The PGE2 was higher in normotensive pregnant control subjects than in nonpregnant subjects. In preeclampsia, PGE2 was reduced to nonpregnant level. PGF2 alpha was the same in preeclampsia and in normotensive pregnancy, but elevated when compared to the normotensive nonpregnant control group. Plasma concentrations of renin and aldosterone were increased during pregnancy, but considerably less in preeclampsia than during normotensive pregnancy. NE and E were the same as in nonpregnant subjects during both hypertensive and normotensive pregnancy. All parameters were normal 3 months after delivery. There were no correlations between PGE2, PGF2 alpha, plasma concentrations of renin, aldosterone, NE, or E and blood pressure level in third trimester either in preeclampsia or in normotensive pregnancy. PGE2 was positively correlated to plasma concentrations of renin. It is suggested that the lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion. It is hypothesized that preeclampsia is a state of prostaglandin deficiency. The changes in the renin-aldosterone system may be secondary to changes in prostaglandin concentration both in preeclampsia and normotensive pregnancy.

  18. Prostaglandins before caesarean section for preventing neonatal respiratory distress.

    PubMed

    Motaze, Nkengafac V; Mbuagbaw, Lawrence; Young, Taryn

    2013-11-11

    Respiratory distress (RD) can occur in both preterm and term neonates born through normal vaginal delivery or caesarean section (CS). It accounts for about 30% of neonatal deaths and can occur at any time following birth. Respiratory distress syndrome (RDS), transient tachypnoea (rapid breathing) of the newborn and persistent pulmonary hypertension (increased blood pressure of pulmonary vessels) of the newborn are the most frequent clinical presentations of neonatal RD. Prostaglandins are used in routine obstetric practice to ripen the uterine cervix and to trigger labour, with those of the E series being preferred over others due to the fact that they are more uteroselective. Administration of prostaglandins to an expectant mother before delivery causes reabsorption of lung fluid from the fetal lung and promotes surfactant secretion by inducing a catecholamine surge. As a result, significant reduction in neonatal respiratory morbidity following a CS could be obtained, leading to reduced long-term complications such as bronchopulmonary dysplasia (chronic lung disease with lung tissue modification) and asthma. The objective of this review was to determine if administration of prostaglandins before CS can improve respiratory outcomes of newborns. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013). We also searched three clinical trial registries; ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry and the WHO Clinical Trials Registry Platform (ICTRP), for ongoing studies (24 June 2013). We included all published and unpublished randomised controlled trials comparing the use of prostaglandins with other treatments (including placebo) to reduce neonatal respiratory morbidity. Participants were pregnant women with an indication for a CS, and we compared administration of prostaglandins prior to CS with no treatment, placebo or another treatment. Two review authors independently assessed studies for inclusion

  19. Learning from Expert Elicitation in Climate Change

    NASA Astrophysics Data System (ADS)

    Morgan, M. G.

    2009-12-01

    Since the early 1990's the author has been involved in the design and execution of six detailed expert elicitations that, among other things, have obtained subjective judgments from experts that reflect their best judgment in the form of subjective probability density functions, about the value of key climate variables, climate impacts and a technology for mitigation (Morgan and Keith, 1995; Morgan Pitelka and Shevliakova, 2001; Morgan, Adams and Keith, 2006; Zickfeld et al, 2007; Curtright, Morgan and Keith, 2008; Zickfeld, Morgan Keith and Frame, in review). This paper builds on that experience to draw insights about the design and use of expert elicitation in the assessment and analysis of climate change and its impacts. Several trends in responses will be noted. Methodological pitfalls will be discussed. Comparisons will be drawn with the consensus-based methods employed by IPCC, which appear to have produced tighter uncertainty bounds than individual elicitation. The paper will close with thoughts on the possible use of expert elicitation in future IPCC assessments. Support for this work is from the Climate Decision Making Center through a cooperative agreement between the National Science Foundation (SES-0345798) and Carnegie Mellon University. References: M. Granger Morgan and David Keith, "Subjective Judgments by Climate Experts," Environmental Science & Technology, 29(10), 468A-476A, October 1995. M. Granger Morgan, Louis F. Pitelka and Elena Shevliakova, "Elicitation of Expert Judgments of Climate Change Impacts on Forest Ecosystems," Climatic Change, 49, 279-307, 2001. M. Granger Morgan, Peter Adams, and David W. Keith, "Elicitation of Expert Judgments of Aerosol Forcing," Climatic Change, 75, 195-214, 2006. Kirsten Zickfeld, Anders Levermann, Till Kuhlbrodt. Stefan Rahmstorf, M. Granger Morgan and David Keith, "Expert Judgements on the Response on the Atlantic Meridional Overturning Circulation to Climate Change," Climatic Change, 82, 235-265, 2007

  20. [Secretion of inflammatory cytokines and prostaglandins by fetal trophoblast cells induces uterine contraction and labor onset].

    PubMed

    Steinbron, A; Günes, H; Lechner, B; Halberstadt, E

    1995-01-01

    Induce infection-associated cytokines intrauterine secretion of prostaglandins and term labor? Concentrations of Il-6, Il-1 beta, TNF-alpha, PGF2 and PGF2 alpha were determined in cervical secretions and amniotic fluid during spontaneous term labor. The supernatant of amnion-, chorion-, decidua- and trophoblast cells, cultured after elective cesarean section or spontaneous delivery, was analysed for cytokine- and prostaglandin activity. Term labor always is associated with intrauterine cytokine- and prostaglandin release. Increased production of cytokines and prostaglandins in case of normal term labor only was found by fetal trophoblast cells. Signal for parturition is of trophoblast and therefore of fetal origin.

  1. Efficacy of the selective prostaglandin synthase type 2 inhibitor nimesulide in blocking basal prostaglandin production and delaying glucocorticoid-induced premature labor in sheep.

    PubMed

    Poore, K R; Young, I R; Hirst, J J

    1999-05-01

    The purpose of the study was to determine the effects of selective prostaglandin synthase type 2 inhibitors on basal prostaglandin concentrations in the fetal and maternal circulations and on the labor-associated increase in prostaglandin production in sheep. The effects of maternal nimesulide (0.01, 0.1, and 1 mg/kg) and 6-methoxy-2-naphthylacetic acid (1, 5, and 10 mg/kg) administration were examined (n = 5) at 134 +/- 1 days' gestation. At 138 days' gestation premature labor was induced by fetal dexamethasone infusion (1 mg/d). Ewes were treated with either vehicle or nimesulide infusion (20 mg. d-1. kg-1, n = 5 per group). Nimesulide and 6-methoxy-2-naphthylacetic acid decreased basal prostaglandin production in a concentration-dependent manner. Delivery of nimesulide-treated ewes was delayed by >/=17 hours with respect to that of control ewes (53.9 +/- 2.6 hours). In 2 nimesulide-treated ewes labor did not progress to delivery despite membrane rupture. The increase in prostaglandin concentrations usually seen during dexamethasone-induced labor was abolished in nimesulide-treated ewes and also in their fetuses. Highly selective inhibitors of prostaglandin endoperoxidase H synthase 2 may be required to spare fetal prostaglandin production and limit potential side effects during the suppression of preterm labor.

  2. Eliciting nicotine craving with virtual smoking cues.

    PubMed

    Gamito, Pedro; Oliveira, Jorge; Baptista, André; Morais, Diogo; Lopes, Paulo; Rosa, Pedro; Santos, Nuno; Brito, Rodrigo

    2014-08-01

    Craving is a strong desire to consume that emerges in every case of substance addiction. Previous studies have shown that eliciting craving with an exposure cues protocol can be a useful option for the treatment of nicotine dependence. Thus, the main goal of this study was to develop a virtual platform in order to induce craving in smokers. Fifty-five undergraduate students were randomly assigned to two different virtual environments: high arousal contextual cues and low arousal contextual cues scenarios (17 smokers with low nicotine dependency were excluded). An eye-tracker system was used to evaluate attention toward these cues. Eye fixation on smoking-related cues differed between smokers and nonsmokers, indicating that smokers focused more often on smoking-related cues than nonsmokers. Self-reports of craving are in agreement with these results and suggest a significant increase in craving after exposure to smoking cues. In sum, these data support the use of virtual environments for eliciting craving.

  3. Elicitation of secondary metabolism in actinomycetes.

    PubMed

    Abdelmohsen, Usama Ramadan; Grkovic, Tanja; Balasubramanian, Srikkanth; Kamel, Mohamed Salah; Quinn, Ronald J; Hentschel, Ute

    2015-11-01

    Genomic sequence data have revealed the presence of a large fraction of putatively silent biosynthetic gene clusters in the genomes of actinomycetes that encode for secondary metabolites, which are not detected under standard fermentation conditions. This review focuses on the effects of biological (co-cultivation), chemical, as well as molecular elicitation on secondary metabolism in actinomycetes. Our review covers the literature until June 2014 and exemplifies the diversity of natural products that have been recovered by such approaches from the phylum Actinobacteria.

  4. Voltage transients elicited by brief chilling

    NASA Technical Reports Server (NTRS)

    Pickard, B. G.

    1984-01-01

    Chilling auxin-depleted, etiolated stems of Pisum sativum L. to 4 degrees C for 60 s enhanced the production of previously described voltage transients 20-fold. It is postulated that plasmalemmal permeability to Ca2+ is increased at low temperature, permitting influx of the ion from the apoplast to the cytosol and thereby promoting production of transients. Heating to 40 degrees C or 45 degrees C elicits no increase in transients, and heating to 50 degrees C leads to loss of turgor.

  5. Essays on probability elicitation scoring rules

    NASA Astrophysics Data System (ADS)

    Firmino, Paulo Renato A.; dos Santos Neto, Ademir B.

    2012-10-01

    In probability elicitation exercises it has been usual to considerer scoring rules (SRs) to measure the performance of experts when inferring about a given unknown, Θ, for which the true value, θ*, is (or will shortly be) known to the experimenter. Mathematically, SRs quantify the discrepancy between f(θ) (the distribution reflecting the expert's uncertainty about Θ) and d(θ), a zero-one indicator function of the observation θ*. Thus, a remarkable characteristic of SRs is to contrast expert's beliefs with the observation θ*. The present work aims at extending SRs concepts and formulas for the cases where Θ is aleatory, highlighting advantages of goodness-of-fit and entropy-like measures. Conceptually, it is argued that besides of evaluating the personal performance of the expert, SRs may also play a role when comparing the elicitation processes adopted to obtain f(θ). Mathematically, it is proposed to replace d(θ) by g(θ), the distribution that model the randomness of Θ, and do also considerer goodness-of-fit and entropylike metrics, leading to SRs that measure the adherence of f(θ) to g(θ). The implications of this alternative perspective are discussed and illustrated by means of case studies based on the simulation of controlled experiments. The usefulness of the proposed approach for evaluating the performance of experts and elicitation processes is investigated.

  6. Eliciting principles of hazard identification from experts.

    PubMed

    Jelovsek, F R; Mattison, D R; Young, J F

    1990-11-01

    National experts in the field of developmental toxicology were interviewed in order to elicit the principles, or rules-of-thumb, they use in determining if a compound or agent is likely to be a developmental hazard during pregnancy. Several levels of individual and cumulative consensus activity were carried out that resulted in consensus in 71 rules and partial consensus in an additional 24 rules of 145 rules initially elicited. Rules could be divided generically into those affecting the expert's confidence in a piece of scientific evidence and those determining the weight of importance of that evidence in deciding about hazard identification. Topically, the rules also divided into those about the general nature or characteristics of a compound, animal studies testing for an effect of the compound, and human reports about the presence of absence of developmental effects associated with the compound. Several conclusions about the methodology include the following: 1) expert systems must be based on the knowledge of more than one expert; 2) considerable human effort is expended in evaluating the certainty of scientific evidence before combining the evidence for problem solving; 3) how experts use evidence of different degrees of uncertainty in their decisions is a major area that is yet to be determined and that may greatly affect subsequent efforts in artificial intelligence; and 4) knowledge elicitation by interview has limitations but is a workable methodology for medical decision making.

  7. Comparison of prostaglandin E2 gel, prostaglandin E2 pessary and extra-amniotic saline infusion with oxytocin for induction of labour.

    PubMed

    Qamar, Saima; Bashir, Adeela; Ibrar, Faiza

    2012-01-01

    Induction of labour is the intentional initiation of cervical ripening and uterine contraction for the purpose of accomplishing delivery, prior to onset of spontaneous parturition. This study was conducted to compare maternal and neonatal outcome in women induced with Prostaglandin E2 gel, Prostaglandin E2 pessary and extra-amniotic saline infusion with oxytocin at Bishops score < 5. It was a quasi-experimental which was conducted at the Department of Gynaecology and Obstetrics Unit-I, Mother and Child Health Care Centre, Pakistan Institute of Medical Sciences, Islamabad during one year of time. Eighty cases in each group (prostaglandin gel, prostaglandinE2 pessary and extra-amniotic saline infusion with oxytocin) were collected. Systematic sampling was done. First woman admitted was induced with prostaglandin gel, the second one with prostaglandin pessary and the third was induced with extra amniotic saline infusion and oxytocin. The most common indication for induction was post dates followed by PIH. The induction labour interval was less in EASI with oxytocin group (5.18 +/- 3.4) hours, as compared to prostaglandin pessary (8.81 +/- 5.60) hours and prostaglandin gel (8.32 +/- 5.18) hours. Induction delivery interval in EASI with oxytocin was (10 +/- 5.6) hours as compared to prostaglandin pessary (14 +/- 6.3) hours and prostaglandin gel (13 +/- 7.1) hours. This difference was statistically significant. The primigravidas had longer duration of labour than multigravidas. Induction labour interval in primigravidas was (8.2 +/- 5.1) hours while in multigravidas it was (6.7 +/- 5.02) hours. Induction delivery interval was also more in primigravidas (13.6 +/- 6.80) hours as compared to multigravidas (11.4 +/- 6.20) hours. Vaginal delivery rate was 89.2% while the caesarean section rate was 10.4%. The most common indication for caesarean section was foetal distress. There was no significant difference in perinatal morbidity and mortality in the three groups. EASI with

  8. Role of prostaglandins in development of porcine blastocysts.

    PubMed

    Geisert, R D; Rasby, R J; Minton, J E; Wetteman, R P

    1986-02-01

    Rapid elongation of porcine blastocysts between Days 11 to 12 of pregnancy coincides with an increase in uterine luminal content of prostaglandins. The present study evaluated the effect of two prostaglandin synthesis inhibitors (indomethacin and flunixin meglumine) on elongation of porcine blastocysts from spherical to filamentous forms between Day 11 to 12 of pregnancy. Gilts were hemi-hysterectomized on Day 11 of pregnancy. The excised uterine horn was flushed with 0.9% saline and diameter of blastocysts recovered were measured. Immediately following surgery, pregnant gilts were assigned to receive either: 1) vehicle every 4 h, 2) flunixin meglumine (banamine) every 4 h, or 3) indomethacin every 12 h. The remaining uterine horn was removed and flushed after the time of blastocyst elongation estimated for each gilt on basis of blastocyst development in the first horn. Uterine flushings were analyzed for total calcium, protein, acid phosphatase activity, estrone, estradiol-17 beta and prostaglandin F. Pretreatment blastocyst diameter was similar for all groups and ranged from 1 mm to 20 mm. Treatment of gilts with either banamine or indomethacin effectively inhibited (P less than 0.001) the increase in uterine luminal content of PGF. Total calcium, estrone and estradiol-17 beta were not influenced by treatment. Total uterine luminal protein and acid phosphatase activity were reduced (P less than 0.05) in banamine treated gilts compared to those receiving vehicle or indomethacin treatments. Although total PGF recovered in uterine flushings was reduced during the period of blastocyst elongation, treatment with PGF synthetase inhibitors failed to block rapid elongation of blastocysts from the spherical to filamentous forms.

  9. Screening of Zulu medicinal plants for prostaglandin-synthesis inhibitors.

    PubMed

    Jäger, A K; Hutchings, A; van Staden, J

    1996-06-01

    Aqueous and ethanolic extracts of 39 plants used in traditional Zulu medicine to treat headache or inflammatory diseases were screened for prostaglandin-synthesis inhibitors. Extracts were tested in an in vitro assay for cyclooxygenase inhibitors. In general, ethanolic extracts caused higher inhibition than aqueous extracts. Two-thirds of the plants screened had high inhibitory activity. The highest inhibition was obtained with ethanolic extracts of Bidens pilosa, Eucomis autumnalis, Harpephyllum caffrum, Helichrysum nudifolium, Leonotis intermedia, L. leonorus, Ocotea bullata, Rumex saggitatus, Solanum mauritianum, Synadenium cupulare and Trichilia dregeana.

  10. Prostaglandin E2 regulates angiogenesis via activation of fibroblast growth factor receptor-1.

    PubMed

    Finetti, Federica; Solito, Raffaella; Morbidelli, Lucia; Giachetti, Antonio; Ziche, Marina; Donnini, Sandra

    2008-01-25

    Prostaglandin E(2) (PGE(2)) behaves as a mitogen in epithelial tumor cells as well as in many other cell types. We investigated the actions of PGE(2) on microvascular endothelial cells (capillary venular endothelial cells) with the purpose of delineating the signaling pathway leading to the acquisition of the angiogenic phenotype and to new vessel formation. PGE(2) (100 nM) produced activation of the fibroblast growth factor receptor 1 (FGFR-1), as measured by its phosphorylation, but not of vascular endothelial growth factor receptor 2. PGE(2) stimulated the EP3 subtype receptor, as deduced by abrogation of EP3 Galpha(i) subunit activity through pertussis toxin. Consistent with this result, in human umbilical venular endothelial cells missing the EP3 receptor, PGE(2) did not phosphorylate FGFR-1. Upon binding to its receptor, PGE(2) initiated an autocrine/paracrine signaling cascade involving the intracellular activation of c-Src, activation of matrix metalloproteinase (predominantly MMP2), which in turn caused the mobilization of membrane-anchored fibroblast growth factor-2 (FGF-2). In fact, in cells unable to release FGF-2 the transfection with both FGFR-1 and EP3 did not result in FGFR-1 phosphorylation in response to PGE(2). Relevance for the FGF2-FGFR-1 system was highlighted by confocal analysis, showing receptor internalization after cell exposure to the prostanoid. ERK1/2 appeared to be the distal signal involved, its phosphorylation being sensitive to either cSrc inhibitor or FGFR-1 blocker. Finally, PGE(2) stimulated cell migration and capillary formation in aortic rings, which were severely reduced by inhibitors of signaling molecules or by receptor antagonist. In conclusion, this study provides evidence for the involvement of FGFR-1 through FGF2 in eliciting PGE(2) angiogenic responses. This signaling pattern is similar to the autocrine-paracrine mechanism which operates in endothelial cells to support neovascular growth.

  11. Formulation and in vitro evaluation of niacin-loaded nanoparticles to reduce prostaglandin mediated vasodilatory flushing.

    PubMed

    Cooper, D L; Carmical, J A; Panus, P C; Harirforoosh, S

    2015-10-01

    Niacin, activating G-protein coupled receptor (GPR) 109A, stimulates release of vasodilatory prostaglandins (PGs) such as PGE2 which can elicit niacin-associated flushing side effects. Poly-lactic-co-glycolic acid (PLGA) and poly-lactic acid (PLA) are used in nanoparticle (NP) drug delivery to reduce adverse effects and modulate drug release. Our study evaluated the in vitro effects of niacin-loaded PLGA or PLA-NPs on PGE2 expression in whole human blood as a model for niacin-induced flushing. NPs were formulated using a solvent evaporation process and characterized by size, polydispersity, zeta potential, drug entrapment, morphology, and drug release. NP in vitro effects on PGE2 release were measured via ELISA analysis. PLGA-NPs demonstrated the lowest NP size (66.7 ± 0.21 nm) with the highest zeta potential and percent drug entrapment (42.00 ± 1.62 mV and 69.09 ± 0.29%, respectively) when compared to PLA-NPs (130.4 ± 0.66 nm, 27.96 ± 0.18 mV, 69.63 ± 0.03 %, respectively). In vitro release studies showed that PLGA-NPs underwent significant reductions in cumulative drug release when compared to PLA-NPs (p < 0.05). Furthermore, when compared to plain niacin, PLGA-NPs significantly reduced in vitro PGE2 release (p < 0.05). These results support the use of PLGA-NPs as a novel method of delivery for reducing niacin-associated flushing.

  12. Enteral feeding in prostaglandin-dependent neonates: is it a safe practice?

    PubMed

    Willis, Lisa; Thureen, Patti; Kaufman, Jonathan; Wymore, Erica; Skillman, Heather; da Cruz, Eduardo

    2008-12-01

    In many centers presurgical term neonates with prostaglandin-dependent cardiac lesions experience nutritional deficiency because of postponed enteral feeds. We recently adopted early enteral feeding in these infants. This retrospective study demonstrates feeding tolerance in 33 of 34 neonates fed enterally while receiving prostaglandin, suggesting the safety of this practice.

  13. The effect of prostaglandin E1 analog misoprostol on chronic cyclosporin nephrotoxicity.

    PubMed

    John, E G; Fornell, L C; Radhakrishnan, J; Anutrakulchai, S; Jonasson, O

    1993-11-01

    Cyclosporin A has markedly improved graft survival in transplant patients but its side effects, such as renal toxicity and hypertension, pose management problems in transplant recipients. This toxicity has been attributed to prostaglandin inhibition. Concurrent administration of misoprostol (a prostaglandin E1 analog) prevents chronic cyclosporin A-induced nephrotoxicity but not hypertension in rats.

  14. Unsaturated Zone Flow Model Expert Elicitation Project

    SciTech Connect

    Coppersmith, K. J.

    1997-05-30

    This report presents results of the Unsaturated Zone Flow Model Expert Elicitation (UZFMEE) project at Yucca Mountain, Nevada. This project was sponsored by the US Department of Energy (DOE) and managed by Geomatrix Consultants, Inc. (Geomatrix), for TRW Environmental Safety Systems, Inc. The objective of this project was to identify and assess the uncertainties associated with certain key components of the unsaturated zone flow system at Yucca Mountain. This assessment reviewed the data inputs, modeling approaches, and results of the unsaturated zone flow model (termed the ''UZ site-scale model'') being developed by Lawrence Berkeley National Laboratory (LBNL) and the US Geological Survey (USGS). In addition to data input and modeling issues, the assessment focused on percolation flux (volumetric flow rate per unit cross-sectional area) at the potential repository horizon. An understanding of unsaturated zone processes is critical to evaluating the performance of the potential high-level nuclear waste repository at Yucca Mountain. A major goal of the project was to capture the uncertainties involved in assessing the unsaturated flow processes, including uncertainty in both the models used to represent physical controls on unsaturated zone flow and the parameter values used in the models. To ensure that the analysis included a wide range of perspectives, multiple individual judgments were elicited from members of an expert panel. The panel members, who were experts from within and outside the Yucca Mountain project, represented a range of experience and expertise. A deliberate process was followed in facilitating interactions among the experts, in training them to express their uncertainties, and in eliciting their interpretations. The resulting assessments and probability distributions, therefore, provide a reasonable aggregate representation of the knowledge and uncertainties about key issues regarding the unsaturated zone at the Yucca Mountain site.

  15. Antagonist-Elicited Cannabis Withdrawal in Humans

    PubMed Central

    Gorelick, David A.; Goodwin, Robert S.; Schwilke, Eugene; Schwope, David M.; Darwin, William D.; Kelly, Deanna L.; McMahon, Robert P.; Liu, Fang; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A.

    2013-01-01

    Cannabinoid CB1 receptor antagonists have potential therapeutic benefits, but antagonist-elicited cannabis withdrawal has not been reported in humans. Ten male daily cannabis smokers received 8 days of increasingly frequent 20-mg oral Δ9-tetrahydrocannabinol (THC) dosages (40–120 mg/d) around-the-clock to standardize cannabis dependence while residing on a closed research unit. On the ninth day, double-blind placebo or 20- (suggested therapeutic dose) or 40-mg oral rimonabant, a CB1-cannabinoid receptor antagonist, was administered. Cannabis withdrawal signs and symptoms were assessed before and for 23.5 hours after rimonabant. Rimonabant, THC, and 11-hydroxy-THC plasma concentrations were quantified by mass spectrometry. The first 6 subjects received 20-mg rimonabant (1 placebo); the remaining 4 subjects received 40-mg rimonabant (1 placebo). Fourteen subjects enrolled; 10 completed before premature termination because of withdrawal of rimonabant from clinical development. Three of 5 subjects in the 20-mg group, 1 of 3 in the 40-mg group, and none of 2 in the placebo group met the prespecified withdrawal criterion of 150% increase or higher in at least 3 visual analog scales for cannabis withdrawal symptoms within 3 hours of rimonabant dosing. There were no significant associations between visual analog scale, heart rate, or blood pressure changes and peak rimonabant plasma concentration, area-under-the-rimonabant-concentration-by-time curve (0–8 hours), or peak rimonabant/THC or rimonabant/(THC + 11-hydroxy-THC) plasma concentration ratios. In summary, prespecified criteria for antagonist-elicited cannabis withdrawal were not observed at the 20- or 40-mg rimonabant doses. These data do not preclude antagonist-elicited withdrawal at higher rimonabant doses. PMID:21869692

  16. Antagonist-elicited cannabis withdrawal in humans.

    PubMed

    Gorelick, David A; Goodwin, Robert S; Schwilke, Eugene; Schwope, David M; Darwin, William D; Kelly, Deanna L; McMahon, Robert P; Liu, Fang; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A

    2011-10-01

    Cannabinoid CB1 receptor antagonists have potential therapeutic benefits, but antagonist-elicited cannabis withdrawal has not been reported in humans. Ten male daily cannabis smokers received 8 days of increasingly frequent 20-mg oral Δ⁹-tetrahydrocannabinol (THC) dosages (40-120 mg/d) around-the-clock to standardize cannabis dependence while residing on a closed research unit. On the ninth day, double-blind placebo or 20- (suggested therapeutic dose) or 40-mg oral rimonabant, a CB1-cannabinoid receptor antagonist, was administered. Cannabis withdrawal signs and symptoms were assessed before and for 23.5 hours after rimonabant. Rimonabant, THC, and 11-hydroxy-THC plasma concentrations were quantified by mass spectrometry. The first 6 subjects received 20-mg rimonabant (1 placebo); the remaining 4 subjects received 40-mg rimonabant (1 placebo). Fourteen subjects enrolled; 10 completed before premature termination because of withdrawal of rimonabant from clinical development. Three of 5 subjects in the 20-mg group, 1 of 3 in the 40-mg group, and none of 2 in the placebo group met the prespecified withdrawal criterion of 150% increase or higher in at least 3 visual analog scales for cannabis withdrawal symptoms within 3 hours of rimonabant dosing. There were no significant associations between visual analog scale, heart rate, or blood pressure changes and peak rimonabant plasma concentration, area-under-the-rimonabant-concentration-by-time curve (0-8 hours), or peak rimonabant/THC or rimonabant/(THC + 11-hydroxy-THC) plasma concentration ratios. In summary, prespecified criteria for antagonist-elicited cannabis withdrawal were not observed at the 20- or 40-mg rimonabant doses. These data do not preclude antagonist-elicited withdrawal at higher rimonabant doses.

  17. Occurrence of prostaglandins and other eicosanoids in parasites and their role in host-parasite interaction.

    PubMed

    Szkudliński, J

    2000-01-01

    Prostaglandins have been already pretty well recognized as metabolic regulators in vertebebrata tissues mainly in mammals. I.ess reports concerned the occurrence of prostaglandins in invertebrates. In the present review we summarise literature data about the presence of prostaglandins and other eicosanoids in various groups of parasites and their possible role in host-parasite interaction. Prostaglandins have also been found in very primitive organisms as bacteria, varions plants and protozoa. We summarise that prostaglandins seem to be a very ancient group, going back to the roots of evolution. They are as universal in cell physiology as DNA in genetics. In host-parasiter eicosanoids also parasitic origin, play an important role as a modulators of hosts immune responsiveness.

  18. Eliciting promises from children reduces cheating.

    PubMed

    Heyman, Gail D; Fu, Genyue; Lin, Jianyan; Qian, Miao K; Lee, Kang

    2015-11-01

    Widespread cheating can undermine rules that are necessary for maintaining social order. Preventing cheating can be a challenge, especially with regard to children, who as a result of their limited executive function skills may have particular difficulty with resisting temptation to cheat. We examined one approach designed to help children resist this temptation: eliciting a verbal commitment to not cheat. We tested 4- to 7-year-olds (total N = 330) and found that starting at 5 years of age, a verbal commitment to not cheat led to a substantial reduction in cheating. The results suggest that verbal commitments can be used to help children overcome temptations and comply with rules.

  19. Prostaglandin EP3 receptor superactivates adenylyl cyclase via the Gq/PLC/Ca2+ pathway in a lipid raft-dependent manner.

    PubMed

    Yamaoka, Kumiko; Yano, Akiko; Kuroiwa, Kenji; Morimoto, Kazushi; Inazumi, Tomoaki; Hatae, Noriyuki; Tabata, Hiroyuki; Segi-Nishida, Eri; Tanaka, Satoshi; Ichikawa, Atsushi; Sugimoto, Yukihiko

    2009-11-27

    We previously demonstrated that prostaglandin EP3 receptor augments EP2-elicited cAMP formation in COS-7 cells in a G(i/o)-insensitive manner. The purpose of our current study was to identify the signaling pathways involved in EP3-induced augmentation of receptor-stimulated cAMP formation. The enhancing effect of EP3 receptor was irrespective of the C-terminal structure of the EP3 isoform. This EP3 action was abolished by treatment with inhibitors for phospholipase C and intracellular Ca(2+)-related signaling molecules such as U73122, staurosporine, 2-APB and SK&F 96365. Indeed, an EP3 agonist stimulated IP(3) formation and intracellular Ca(2+) mobilization, which was blocked by U73122, but not by pertussis toxin. The enhancing effect by EP3 on cAMP formation was mimicked by both a Ca(2+) ionophore and the activation of a typical G(q)-coupled receptor. Moreover, EP3 was exclusively localized to the raft fraction in COS-7 cells and EP3-elicited augmentation of cAMP formation was abolished by cholesterol depletion and introduction of a dominant negative caveolin-1 mutant. These results suggest that EP3 elicits adenylyl cyclase superactivation via G(q)/phospholipase C activation and intracellular Ca(2+) mobilization in a lipid raft microdomain-dependent manner.

  20. The Effect of Chronic Sodium Loading and Sodium Restriction on Plasma Prostaglandin A, E and F Concentrations in Normal Humans

    PubMed Central

    Zusman, Randall M.; Spector, David; Caldwell, Burton V.; Speroff, Leon; Schneider, George; Mulrow, Patrick J.

    1973-01-01

    It has been suggested that prostaglandins may be involved in the control of sodium homeostasis. Prostaglandin A and prostaglandin E have been shown to increase renal blood flow and urinary sodium excretion and prostaglandin A has been shown to stimulate aldosterone release. The purpose of this study was to determine the effect of chronic sodium loading and sodium restriction on plasma prostaglandin A, E, and F concentrations. Seven normal human volunteers were placed on three sodium intake diets: (a) ad lib. sodium intake, (b) high sodium intake, and (c) low sodium intake. Plasma prostaglandin A, E, and F concentrations were measured by radioimmunoassay. Mean prostaglandin A levels on the ad lib. diet were 1.60 ng/ml. Prostaglandin A levels decreased 49% to 0.82 ng/ml on the high sodium intake and increased 34% to 2.14 ng/ml on the low sodium intake. Prostaglandin A levels increased 161% on the low sodium diet in comparison with levels on the high sodium diet. Plasma prostaglandin E and F concentrations did not change significantly during variation in sodium intake. These results show that dietary sodium content markedly effects plasma prostaglandin A levels and that prostaglandins may play a role in the physiologic mechanism of sodium homeostasis. PMID:4700484

  1. Optimising daytime deliveries when inducing labour using prostaglandin vaginal inserts.

    PubMed

    Miller, Hugh; Goetzl, Laura; Wing, Deborah A; Powers, Barbara; Rugarn, Olof

    2016-01-01

    To determine induction start time(s) that would maximise daytime deliveries when using prostaglandin vaginal inserts. Women enrolled into the Phase III trial, EXPEDITE (clinical trial registration: NCT01127581), had labour induced with either a misoprostol or dinoprostone vaginal insert (MVI or DVI). A secondary analysis was conducted to determine the optimal start times for induction by identifying the 12-h period with the highest proportion of deliveries by parity and treatment. Optimal start times for achieving daytime deliveries when using MVI appear to be 19:00 in nulliparae and 23:00 in multiparae. Applying these start times, the median time of onset of active labour would be approximately 08:30 for both parities and the median time of delivery would be the following day at approximately 16:30 for nulliparae and 12:00 (midday) for multiparae. Optimal start times when using DVI appear to be 07:00 for nulliparae and 23:00 for multiparae. Using these start times, the median time of onset of active labour would be the following day at approximately 04:00 and 11:50, and the median time of delivery would be approximately 13:40 and 16:10, respectively. When optimising daytime deliveries, different times to initiate induction of labour may be appropriate depending on parity and the type of retrievable prostaglandin vaginal insert used.

  2. Prostaglandins are important in thermoregulation of a reptile (Pogona vitticeps).

    PubMed

    Seebacher, Frank; Franklin, Craig E

    2003-08-07

    The effectiveness of behavioural thermoregulation in reptiles is amplified by cardiovascular responses, particularly by differential rates of heart beat in response to heating and cooling (heart-rate hysteresis). Heart-rate hysteresis is ecologically important in most lineages of ectothermic reptile, and we demonstrate that heart-rate hysteresis in the lizard Pogona vitticeps is mediated by prostaglandins. In a control treatment (administration of saline), heart rates during heating were significantly faster than during cooling at any given body temperature. When cyclooxygenase 1 and 2 enzymes were inhibited, heart rates during heating were not significantly different from those during cooling. Administration of agonists showed that thromboxane B(2) did not have a significant effect on heart rate, but prostacyclin and prostaglandin F(2alpha) caused a significant increase (3.5 and 13.6 beats min(-1), respectively) in heart rate compared with control treatments. We speculate that heart-rate hysteresis evolved as a thermoregulatory mechanism that may ultimately be controlled by neurally induced stimulation of nitric oxide production, or maybe via photolytically induced production of vitamin D.

  3. Review on prostaglandin and oxytocin activity in preterm labor.

    PubMed

    Ivanisević, M; Djelmis, J; Buković, D

    2001-12-01

    The principal difference between term and preterm labor is how they are activated. It has been proposed that term labor results from physiological activation of the common terminal pathway, whereas preterm labor is a pathological condition caused by multiple etiologies that activate one or more of the components of this pathway. Increased uterine contractility at preterm labor results from activation and stimulation of the myometrium. Myometrium is stimulated by increased concentrations ofprostaglandins and oxytocin. Increased production of stimulatory prostaglandins by intrauterine tissues is generally considered a central component of the cascade of events leading to preterm parturition. Prostaglandins act to mediate cervical ripening and to stimulate uterine contractions and indirectly to increase fundally dominant myometrial contractility by up regulation of gap junctions, oxytocin and arginine vasopressin receptors and synchronizations of contractions. The authors tried to explain the role and influence of oxytocin in human parturition, as well as the novel therapy in inhibiting the contractions in preterm labor. The selective oxytocin inhibitor was tested in vitro on human myometrium and decidua by the author of this article among the first in the world.

  4. Enhancement of neural and thermal vasoconstriction by prostaglandin B1.

    PubMed

    Engelbrecht, J A; Greenberg, S; Wilson, W R

    1975-03-01

    The vascular effects of prostaglandin B1 (PGB1) were studied during constant-flow perfusion of the canine hindpaw. The effects of PGB1 (50-200 ng/kg/min ia) on systemic and hindpaw perfusion pressures and on responses to local cooling (4 degrees C for 90 sec) and local heating (45 degrees C for 60 sec) were measured in 15 dogs. PGB1 (50-100 ng/kg/min) decreased perfusion pressure without any significant effect on systemic arterial pressure. Higher concentrations of PGB1 (200 ng/kg/min) elevated perfusion pressure to control values. The pressor responses to local cooling were increased from 11 to 32 mmHg while the dilator responses to local heating and nitroglycerin were reduced during infusions of PGB1. PGB1 also enhanced the pressor responses to norepinephrine or tyramine. These findings support the conclusions that (1) low concentrations of prostaglandin B1 enhance neurotransmitter release with minimal effects on vascular smooth muscle cells and (2) these effects are not secondary to increased perfusion pressures or vascular wall stresses since infusions of PGB1 resulted in vasodilation.

  5. Canine gastric mucosal vasodilation with prostaglandins and histamine analogs

    SciTech Connect

    Gerber, J.G.; Nies, A.S.

    1982-10-01

    The effect of direct intragastric artery infusion of prostaglandins E2 and I2, arachidonic acid, dimaprit (histamine H2 agonist), and 2',2'-pyridylethylamine (histamine H1 agonist) on gastric mucosal blood flow was examined in dogs to elucidate the relationship between gastric secretory state and mucosal blood flow in dogs. These compounds were chosen because of their diverse effect on gastric acid secretion. Gastric fundus blood flow was measured both electromagnetically with a flow probe around the left gastric artery which supplies the fundus almost exclusively, and by the radioactive microsphere technique. Intraarterial infusion of all the compounds resulted in gastric mucosal vasodilation even though PGE2, PGI2, and arachidonic acid inhibit gastric acid secretion, dimaprit stimulated gastric acid secretion, and 2',2'-pyridylethylamine does not affect gastric acid secretion. There was total agreement in the blood flow measurements by the two different techniques. Our data suggest that gastric acid secretion and gastric vasodilation are independently regulated. In addition, the validity of the studies in which the aminopyrine clearance indicates that prostaglandins are mucosal vasoconstrictors needs to be questioned because of the reliance of those measurements on the secretory state of the stomach.

  6. Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways.

    PubMed

    Guan, S-M; Fu, S-M; He, J-J; Zhang, M

    2011-01-01

    Prostaglandin E(2) (PGE(2)) plays important roles in the bone resorption of inflammatory diseases such as rheumatoid arthritis and periodontitis via specific prostaglandin receptors (i.e., EP1-EP4). In this study, the authors examined whether Prevotella intermedia regulates PGE(2) production and EP expression in human periodontal ligament fibroblasts (hPDLs); they also explored the potential signaling pathways involved in PGE(2) production. P. intermedia induced PGE(2) production and cyclooxygenase-2 (COX-2) expression in a dose- and time-dependent manner. Indomethacin and NS-398 completely abrogated the P. intermedia-induced PGE(2) production without modulating COX-2 expression. Specific inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, phosphatidylinositol 3-kinase, and protein kinase C--but not c-AMP and protein kinase A--significantly attenuated the P. intermedia-induced COX-2 and PGE(2) expression. P. intermedia reduced EP1 expression in a concentration- and time-dependent manner. The results indicate that the COX-2-dependent induction of PGE(2) by P. intermedia in hPDLs is mediated by multiple signaling pathways.

  7. Microsomal prostaglandin E2 synthase-1 inhibitors: a patent review.

    PubMed

    Psarra, Anastasia; Nikolaou, Aikaterini; Kokotou, Maroula G; Limnios, Dimitris; Kokotos, George

    2017-09-01

    Microsomal prostaglandin E2 synthase-1 (mPGES-1) catalyzes the terminal step of prostaglandin E2 (PGE2) generation. It is strongly upregulated in inflamed tissues and overexpressed in tumors and it has been recognized as a key enzyme in inflammatory diseases such as arthritis, atherosclerosis, stroke and cancer. Thus, a great effort has been devoted in developing synthetic mPGES-1 inhibitors as novel anti-inflammatory agents. Areas covered: This review article summarizes the mPGES-1 inhibitors presented in patent literature from 2000 to August 2016 and their biological evaluation, discussing their activities in vitro and in vivo. Expert opinion: The side effects of NSAIDs and COX-2 inhibitors on the gastrointestinal tract and the cardiovascular system showcase the urgent need for the discovery of novel potent and safe anti-inflammatory drugs. mPGES-1 inhibitors may present superior safety in comparison to existing anti-inflammatory drugs. The first synthetic inhibitor of mPGES-1 was reported in 2001 and up to now a variety of structurally different inhibitors has been developed. However, only recently two inhibitors entered clinical trials and none has reached yet the market. More preclinical and clinical studies on mPGES-1 inhibitors are needed to realize if indeed they may become novel agents for the treatment of inflammation and cancer.

  8. Prostaglandin signaling regulates ciliogenesis by modulating intraflagellar transport

    PubMed Central

    Jin, Daqing; Ni, Terri T.; Sun, Jianjian; Wan, Haiyan; Amack, Jeffrey D.; Yu, Guangju; Fleming, Jonathan; Chiang, Chin; Li, Wenyan; Papierniak, Anna; Cheepala, Satish; Conseil, Gwenaëlle; Cole, Susan P.C.; Zhou, Bin; Drummond, Iain A.; Schuetz, John D.; Malicki, Jarema; Zhong, Tao P.

    2014-01-01

    Cilia are microtubule-based organelles that mediate signal transduction in a variety of tissues. Despite their importance, the signaling cascades that regulate cilia formation remain incompletely understood. Here we report that prostaglandin signaling affects ciliogenesis by regulating anterograde intraflagellar transport (IFT). Zebrafish leakytail (lkt) mutants display ciliogenesis defects, and lkt locus encodes an ATP-binding cassette transporter (ABCC4). We show that Lkt/ABCC4 localizes to the cell membrane and exports prostaglandin E2 (PGE2), a function that is abrogated by the Lkt/ABCC4T804M mutant. PGE2 synthesis enzyme Cyclooxygenase-1 and its receptor, EP4, which localizes to the cilium and activates cAMP-mediated signaling cascade, are required for cilia formation and elongation. Importantly, PGE2 signaling increases anterograde but not retrograde velocity of IFT and promotes ciliogenesis in mammalian cells. These findings lead us to propose that Lkt/ABCC4-mediated PGE2 signaling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis. PMID:25173977

  9. Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport.

    PubMed

    Jin, Daqing; Ni, Terri T; Sun, Jianjian; Wan, Haiyan; Amack, Jeffrey D; Yu, Guangju; Fleming, Jonathan; Chiang, Chin; Li, Wenyan; Papierniak, Anna; Cheepala, Satish; Conseil, Gwenaëlle; Cole, Susan P C; Zhou, Bin; Drummond, Iain A; Schuetz, John D; Malicki, Jarema; Zhong, Tao P

    2014-09-01

    Cilia are microtubule-based organelles that mediate signal transduction in a variety of tissues. Despite their importance, the signalling cascades that regulate cilium formation remain incompletely understood. Here we report that prostaglandin signalling affects ciliogenesis by regulating anterograde intraflagellar transport (IFT). Zebrafish leakytail (lkt) mutants show ciliogenesis defects, and the lkt locus encodes an ATP-binding cassette transporter (ABCC4). We show that Lkt/ABCC4 localizes to the cell membrane and exports prostaglandin E2 (PGE2), a function that is abrogated by the Lkt/ABCC4(T804M) mutant. PGE2 synthesis enzyme cyclooxygenase-1 and its receptor, EP4, which localizes to the cilium and activates the cyclic-AMP-mediated signalling cascade, are required for cilium formation and elongation. Importantly, PGE2 signalling increases anterograde but not retrograde velocity of IFT and promotes ciliogenesis in mammalian cells. These findings lead us to propose that Lkt/ABCC4-mediated PGE2 signalling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis.

  10. Role of prostaglandins in intrauterine migration of the equine conceptus.

    PubMed

    Stout, T A; Allen, W R

    2001-05-01

    Between at least day 9 and day 16 after ovulation the spherical equine conceptus migrates continuously throughout the uterine lumen, propelled by peristaltic myometrial contractions. This unusually long period of intrauterine movement ensures that the conceptus delivers its anti-luteolytic signal to the entire endometrium to achieve luteostasis. The present experiment tested the hypothesis that prostaglandins stimulate the myometrial contractions that result in the migration of the conceptus. Serial ultrasonographic examinations of the uteri of eight mares performed during 2 h periods between day 10 and day 18 of gestation recorded the pattern of conceptus migration before and after treatment with the cyclo-oxygenase inhibitor flunixin meglumine. Conceptus mobility was high between day 10 and day 14 after ovulation (4.3 +/- 0.8, 4.7 +/- 0.8 and 4.3 +/- 0.9 changes of location per h on day 10, day 12 and day 14, respectively), but was reduced immediately and markedly by an i.v. injection of flunixin meglumine (3.8 +/- 1.5, 1.8 +/- 0.8 and 0.7 +/- 0.2 location changes per h), thereby implicating prostaglandins as the primary stimulus for the myometrial contractions that drive migration of the conceptus.

  11. Prostaglandins, catecholamines, renin and aldosterone during hypertensive and normotensive pregnancy.

    PubMed

    Pedersen, E B; Christensen, N J; Christensen, P; Johannesen, P; Kornerup, H J; Kristensen, S; Lauritsen, J G; Leyssac, P P; Rasmussen, A B; Wohlert, M

    1982-01-01

    Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin (PRC), aldosterone (PAC), noradrenaline (PNA) and adrenaline (PA) were determined in the third trimester of pregnancy, 5 days and 3 months after delivery in preeclampsia and normotensive pregnant and non-pregnant control subjects. PGE2 was higher in pregnant control subjects than in non-pregnant subjects, but reduced to non-pregnant level in preeclampsia. PGF2 alpha was the same in preeclampsia and normotensive pregnancy but higher than in the non-pregnant group. PRC and PAC were increased during pregnancy, but considerably lesser in preeclampsia than during normotensive pregnancy. PNA and PA were the same in all three groups. All parameters were normal 3 months after delivery. There were no correlations between any of the hormones and blood pressure in any of the groups. PGE2 was positively correlated to PRC. The lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion, and the changes in PRC and PAC are supposed to be secondary to changes in PGE2. It is hypothesised that preeclampsia is a state of prostaglandin deficiency.

  12. Role of prostaglandins in marihuana-induced bronchodilation.

    PubMed

    Laviolette, M; Bélanger, J

    1986-01-01

    In vitro evidence suggests that physiological effects of marihuana may be mediated by prostaglandins via the stimulation of phospholipase A2. To verify if marihuana could act by this route in vivo, we tested the effects of acetylsalicylic and mefenamic acids, inhibitors of cyclooxygenase, on marihuana-induced bronchodilation and tachycardia. In 11 healthy volunteers, marihuana smoking (7 mg/kg, 1.7% delta 9-tetrahydrocannabinol) produced a significant increase in specific airway conductance (from 0.262 +/- 0.033 to 0.360 +/- 0.050 s-1 X cm H2O-1, mean +/- SE, p less than 0.01), forced expiratory volume in 1 s (4.02 +/- 0.22-4.27 +/- 0.25 liter, p less than 0.05) and heart rate (73.2 +/- 2.0-108.5 +/- 5.2 beats/min, p less than 0.001). In a second session, acetylsalicylic or mefenamic acid was taken for 30 h before marihuana smoking. No inhibition of marihuana-induced increase of specific airway conductance, forced expiratory volume in 1 s and heart rate was found. These findings suggest that the bronchodilation and the tachycardia induced by marihuana smoking in humans are not mediated by prostaglandins.

  13. Optimising daytime deliveries when inducing labour using prostaglandin vaginal inserts

    PubMed Central

    Miller, Hugh; Goetzl, Laura; Wing, Deborah A.; Powers, Barbara; Rugarn, Olof

    2016-01-01

    Abstract Objective: To determine induction start time(s) that would maximise daytime deliveries when using prostaglandin vaginal inserts. Methods: Women enrolled into the Phase III trial, EXPEDITE (clinical trial registration: NCT01127581), had labour induced with either a misoprostol or dinoprostone vaginal insert (MVI or DVI). A secondary analysis was conducted to determine the optimal start times for induction by identifying the 12-h period with the highest proportion of deliveries by parity and treatment. Results: Optimal start times for achieving daytime deliveries when using MVI appear to be 19:00 in nulliparae and 23:00 in multiparae. Applying these start times, the median time of onset of active labour would be approximately 08:30 for both parities and the median time of delivery would be the following day at approximately 16:30 for nulliparae and 12:00 (midday) for multiparae. Optimal start times when using DVI appear to be 07:00 for nulliparae and 23:00 for multiparae. Using these start times, the median time of onset of active labour would be the following day at approximately 04:00 and 11:50, and the median time of delivery would be approximately 13:40 and 16:10, respectively. Conclusions: When optimising daytime deliveries, different times to initiate induction of labour may be appropriate depending on parity and the type of retrievable prostaglandin vaginal insert used. PMID:25758619

  14. Influence of different prostaglandin applications on cervical rheology.

    PubMed

    Spätling, L; Neuman, M R; Huch, R; Huch, A

    1985-10-01

    The softening effect of prostaglandin (PG) on cervical tissue prior to elective pregnancy termination is quantified by a new technique for the measurement of the elastance and relaxation of the cervix. The method is based on the pressure-volume relation of a compliant balloon placed in the cervical canal. These properties have been measured before and after different applications of prostaglandins in 58 patients electively terminating pregnancy. Application techniques used included high pressure jet application of PGE2 into the tissue of the portio uteri and the internal cervical os (120 micrograms), PGE2 and PGF2 alpha in Tylose gel (100 micrograms/0.5 ml); PGE2 as an intracervical tablet (150 micrograms) and PGE2 oral tablets placed into the posterior fornix of the vagina. Significant changes in cervical elastance were seen with the intracervically applied PGE2 in Tylose gel and the vaginally applied PGE2 tablets. The intracervically applied PGE2 gel also gave significant changes in cervical relaxation. No side effects other than mild cramping (2 patients) were seen with any of the applications in this study.

  15. Prostaglandins are important in thermoregulation of a reptile (Pogona vitticeps).

    PubMed Central

    Seebacher, Frank; Franklin, Craig E

    2003-01-01

    The effectiveness of behavioural thermoregulation in reptiles is amplified by cardiovascular responses, particularly by differential rates of heart beat in response to heating and cooling (heart-rate hysteresis). Heart-rate hysteresis is ecologically important in most lineages of ectothermic reptile, and we demonstrate that heart-rate hysteresis in the lizard Pogona vitticeps is mediated by prostaglandins. In a control treatment (administration of saline), heart rates during heating were significantly faster than during cooling at any given body temperature. When cyclooxygenase 1 and 2 enzymes were inhibited, heart rates during heating were not significantly different from those during cooling. Administration of agonists showed that thromboxane B(2) did not have a significant effect on heart rate, but prostacyclin and prostaglandin F(2alpha) caused a significant increase (3.5 and 13.6 beats min(-1), respectively) in heart rate compared with control treatments. We speculate that heart-rate hysteresis evolved as a thermoregulatory mechanism that may ultimately be controlled by neurally induced stimulation of nitric oxide production, or maybe via photolytically induced production of vitamin D. PMID:12952634

  16. 15-Deoxy-Delta 12,14-prostaglandin J2 inhibition of NF-kappaB-DNA binding through covalent modification of the p50 subunit.

    PubMed

    Cernuda-Morollón, E; Pineda-Molina, E; Cañada, F J; Pérez-Sala, D

    2001-09-21

    Cyclopentenone prostaglandins display anti-inflammatory activities and interfere with the signaling pathway that leads to activation of transcription factor NF-kappaB. Here we explore the possibility that the NF-kappaB subunit p50 may be a target for the cyclopentenone 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)). This prostaglandin inhibited the DNA binding ability of recombinant p50 in a dose-dependent manner. The inhibition required the cyclopentenone moiety and could be prevented but not reverted by glutathione and dithiothreitol. Moreover, a p50 mutant with a C62S mutation was resistant to inhibition, indicating that the effect of 15d-PGJ(2) was probably due to its interaction with cysteine 62 in p50. The covalent modification of p50 by 15d-PGJ(2) was demonstrated by reverse-phase high pressure liquid chromatography and mass spectrometry analysis that showed an increase in retention time and in the molecular mass of 15d-PGJ(2)-treated p50, respectively. The interaction between p50 and 15d-PGJ(2) was relevant in intact cells. 15d-PGJ(2) effectively inhibited cytokine-elicited NF-kappaB activity in HeLa without reducing IkappaBalpha degradation or nuclear translocation of NF-kappaB subunits. 15d-PGJ(2) reduced NF-kappaB DNA binding activity in isolated nuclear extracts, suggesting a direct effect on NF-kappaB proteins. Finally, treatment of HeLa with biotinylated-15d-PGJ(2) resulted in the formation of a 15d-PGJ(2)-p50 adduct as demonstrated by neutravidin binding and immunoprecipitation. These results clearly show that p50 is a target for covalent modification by 15d-PGJ(2) that results in inhibition of DNA binding.

  17. Isolated sleep paralysis elicited by sleep interruption.

    PubMed

    Takeuchi, T; Miyasita, A; Sasaki, Y; Inugami, M; Fukuda, K

    1992-06-01

    We elicited isolated sleep paralysis (ISP) from normal subjects by a nocturnal sleep interruption schedule. On four experimental nights, 16 subjects had their sleep interrupted for 60 minutes by forced awakening at the time when 40 minutes of nonrapid eye movement (NREM) sleep had elapsed from the termination of rapid eye movement (REM) sleep in the first or third sleep cycle. This schedule produced a sleep onset REM period (SOREMP) after the interruption at a high rate of 71.9%. We succeeded in eliciting six episodes of ISP in the sleep interruptions performed (9.4%). All episodes of ISP except one occurred from SOREMP, indicating a close correlation between ISP and SOREMP. We recorded verbal reports about ISP experiences and recorded the polysomnogram (PSG) during ISP. All of the subjects with ISP experienced inability to move and were simultaneously aware of lying in the laboratory. All but one reported auditory/visual hallucinations and unpleasant emotions. PSG recordings during ISP were characterized by a REM/W stage dissociated state, i.e. abundant alpha electroencephalographs and persistence of muscle atonia shown by the tonic electromyogram. Judging from the PSG recordings, ISP differs from other dissociated states such as lucid dreaming, nocturnal panic attacks and REM sleep behavior disorders. We compare some of the sleep variables between ISP and non-ISP nights. We also discuss the similarities and differences between ISP and sleep paralysis in narcolepsy.

  18. Multiple faces elicit augmented neural activity

    PubMed Central

    Puce, Aina; McNeely, Marie E.; Berrebi, Michael E.; Thompson, James C.; Hardee, Jillian; Brefczynski-Lewis, Julie

    2013-01-01

    How do our brains respond when we are being watched by a group of people?Despite the large volume of literature devoted to face processing, this question has received very little attention. Here we measured the effects on the face-sensitive N170 and other ERPs to viewing displays of one, two and three faces in two experiments. In Experiment 1, overall image brightness and contrast were adjusted to be constant, whereas in Experiment 2 local contrast and brightness of individual faces were not manipulated. A robust positive-negative-positive (P100-N170-P250) ERP complex and an additional late positive ERP, the P400, were elicited to all stimulus types. As the number of faces in the display increased, N170 amplitude increased for both stimulus sets, and latency increased in Experiment 2. P100 latency and P250 amplitude were affected by changes in overall brightness and contrast, but not by the number of faces in the display per se. In Experiment 1 when overall brightness and contrast were adjusted to be constant, later ERP (P250 and P400) latencies showed differences as a function of hemisphere. Hence, our data indicate that N170 increases its magnitude when multiple faces are seen, apparently impervious to basic low-level stimulus features including stimulus size. Outstanding questions remain regarding category-sensitive neural activity that is elicited to viewing multiple items of stimulus categories other than faces. PMID:23785327

  19. Galanin-like peptide (GALP) facilitates thermogenesis via synthesis of prostaglandin E2 by astrocytes in the periventricular zone of the third ventricle.

    PubMed

    Kageyama, Haruaki; Endo, Kei; Osaka, Toshimasa; Watanabe, Jun; Wang, Li Hua; Ito, Kazuo; Suzuki, Mamiko; Sakagami, Junichi; Takenoya, Fumiko; Shioda, Seiji

    2013-07-01

    Administration of galanin-like peptide (GALP) leads to a decrease in both total food intake and body weight 24 h after injection, compared to controls. Moreover, GALP induces an increase in core body temperature. To elucidate the mechanism by which GALP exerts its effect on energy homeostasis, urethane-anesthetized rats were intracerebroventricularly injected with GALP or saline, after which oxygen consumption, heart rate, and body temperature were monitored for 4 h. In some cases, animals were also pretreated with the cyclooxygenase (COX) inhibitor, diclofenac, via intracerebroventricular (i.c.v.) or intravenous (i.v.) injection. c-Fos expression in the brain was also examined after injection of GALP, and the levels of COX and prostaglandin E(2) synthetase (PGES) mRNA in primary cultured astrocytes treated with GALP were analyzed by using qPCR. The i.c.v. injection of GALP caused biphasic thermogenesis, an effect which could be blocked by pretreatment with centrally (i.c.v.), but not peripherally (i.v.) administered diclofenac. c-Fos immunoreactivity was observed in astrocytes in the periventricular zone of the third ventricle. GALP treatment also increased COX-2 and cytosolic PGES, but not COX-1, microsomal PGES-1, or microsomal PGES-2 mRNA levels in cultured astrocytes. We, therefore, suggest that GALP elicits thermogenesis via a prostaglandin E(2)-mediated pathway in astrocytes of the central nervous system.

  20. 15-Deoxy-Δ(12,14)-prostaglandin J2 exerts pro- and anti-inflammatory effects in mesangial cells in a concentration-dependent manner.

    PubMed

    Martínez, Alma E; Sánchez-Gómez, Francisco J; Díez-Dacal, Beatriz; Oeste, Clara L; Pérez-Sala, Dolores

    2012-02-01

    Cyclopentenone prostaglandins play a modulatory role in inflammation, in part through their ability to covalently modify key proinflammatory proteins. Using mesangial cells as a cellular model of inflammation we have observed that 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) exerts a biphasic effect on cell activation by cytokines, with nanomolar concentrations eliciting an amplification of nitric oxide (NO) production and iNOS and COX-2 levels, and concentrations of 5 μM and higher inhibiting proinflammatory gene expression. An analog of 15d-PGJ(2) lacking the cyclopentenone structure (9,10-dihydro-15d-PGJ(2)) showed reduced ability to elicit both types of effects, suggesting that the electrophilic nature of 15d-PGJ(2) is important for its biphasic action. Interestingly, the switch from stimulatory to inhibitory actions occurred within a narrow concentration range and correlated with the ability of 15d-PGJ(2) to induce heme oxygenase 1 and γ-GCSm expression. These events are highly dependent on the triggering of the antioxidant response, which is considered as a sensor of thiol group modification. Indeed, the levels of the master regulator of the antioxidant response Nrf2 increased upon treatment with concentrations of 15d-PGJ(2) above 5 μM, an effect that could not be mimicked by 9,10-dihydro-15d-PGJ(2). Thus, an interplay of redox and electrophilic signalling mechanisms can be envisaged by which 15d-PGJ(2), as several other redox mediators, could contribute both to the onset and to the resolution of inflammation in a context or concentration-dependent manner.

  1. Regional distribution of prostaglandin endoperoxide synthase studied by enzyme-linked immunoassay using monoclonal antibodies.

    PubMed

    Yoshimoto, T; Magata, K; Ehara, H; Mizuno, K; Yamamoto, S

    1986-06-11

    Prostaglandin endoperoxide synthase transforms arachidonic acid to prostaglandin H2 via prostaglandin G2. The enzyme purified from bovine vesicular gland was given to mice as antigen, and monoclonal antibodies were raised by the hybridoma technique. Two species of the monoclonal antibody recognizing different sites of the enzyme were utilized to establish a peroxidase-linked immunoassay of prostaglandin endoperoxide synthase. Fab' fragment of one of the antibodies was prepared and conjugated to horseradish peroxidase. The conjugate was then bound to prostaglandin endoperoxide synthase, and the labeled enzyme was precipitated by the addition of the other antibody. The peroxidase activity of the immunoprecipitate correlated linearly with the amount of prostaglandin endoperoxide synthase. This sensitive and convenient method to determine the enzyme amount rather than the enzyme activity was utilized to extensively screen the amount of prostaglandin endoperoxide synthase in various bovine tissues. In addition to vesicular gland, platelets and kidney medulla previously known as rich enzyme sources, the immunoenzymometric assay demonstrated a high content of the enzyme in various parts of alimentary tract and a low but significant amount of enzyme in some parts of brain.

  2. Plasma 8-iso-Prostaglandin F2α concentrations and outcomes after acute intracerebral hemorrhage.

    PubMed

    Du, Quan; Yu, Wen-Hua; Dong, Xiao-Qiao; Yang, Ding-Bo; Shen, Yong-Feng; Wang, Hao; Jiang, Li; Du, Yuan-Feng; Zhang, Zu-Yong; Zhu, Qiang; Che, Zhi-Hao; Liu, Qun-Jie

    2014-11-01

    Higher plasma 8-iso-Prostaglandin F2α concentrations have been associated with poor outcome of severe traumatic brain injury. We further investigated the relationships between plasma 8-iso-Prostaglandin F2α concentrations and clinical outcomes in patients with acute intracerebral hemorrhage. Plasma 8-iso-Prostaglandin F2α concentrations of 128 consecutive patients and 128 sex- and gender-matched healthy subjects were measured by enzyme-linked immunosorbent assay. We assessed their relationships with disease severity and clinical outcomes including 1-week mortality, 6-month mortality and unfavorable outcome (modified Rankin Scale score>2). Plasma 8-iso-Prostaglandin F2α concentrations were substantially higher in patients than in healthy controls. Plasma 8-iso-Prostaglandin F2α concentrations were positively associated with National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume using a multivariate linear regression. It emerged as an independent predictor for clinical outcomes of patients using a forward stepwise logistic regression. ROC curves identified the predictive values of plasma 8-iso-Prostaglandin F2α concentrations, and found its predictive value was similar to NIHSS scores and hematoma volumes. However, it just numerically added the predictive values of NIHSS score and hematoma volume. Increased plasma 8-iso-Prostaglandin F2α concentrations are associated with disease severity and clinical outcome after acute intracerebral hemorrhage. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Long-Term Prostaglandin E1 Infusion for Newborns with Critical Congenital Heart Disease.

    PubMed

    Aykanat, Alper; Yavuz, Taner; Özalkaya, Elif; Topçuoğlu, Sevilay; Ovalı, Fahri; Karatekin, Güner

    2016-01-01

    Prostaglandin E1 is crucial for keeping the patent ductus arteriosus in critical congenital heart disease for the survival and palliation of particularly prematurely born babies until a cardiosurgical intervention is available. In this study, the side effects of prostaglandin E1 in newborns with critical congenital heart disease and clinical outcomes were evaluated. Thirty-five newborns diagnosed with critical congenital heart disease were treated with prostaglandin E1 between January 2012 and September 2014 at our hospital. Patient charts were examined for prostaglandin E1 side effects (metabolic, gastric outlet obstruction, apnea), clinical status, and prognosis. Acquired data were analyzed in the SPSS 20.0 program. Patients with birth weight under 2500 g needed more days of prostaglandin E1 infusion than ones with birthweight over 2500 g (P = 0.016). The ratio of patients with birth weight under 2500 g who received prostaglandin E1 longer than 7 days was higher than the patients with birth weight over 2500 g (P = 0.02). Eighteen side effects were encountered in 11 of 35 patients (31%). Of these side effects, 1 patient had 4, 4 patients had 2, and 6 patients had only 1 side effect. Discontinuation of the therapy was never needed. Prostaglandin E1 is an accepted therapy modality for survival and outcome in critical congenital heart disease in particularly low-birth-weight babies until a surgical intervention is available. Side effects are not less encountered but are almost always manageable, and discontinuation is not needed.

  4. Assessing pragmatic skills in elicited production.

    PubMed

    de Villiers, Peter

    2004-02-01

    In developing a test of pragmatic skills for children ages 4 to 9 years, we focused on a number of functional language skills that are important for children's success in early schooling and for the development of fluent reading and writing. They included (1) wh-question asking, (2) communicative role taking, (3) linking events in a cohesive narrative, and (4) articulating the mental states of the characters in a story. All of the proposed items provide specific referential support and pragmatic motivation for the forms and content to be produced by the child. The pictured materials and elicitation prompts constrain the range of appropriate utterances, so the children's productions are more easily scored than an open-ended spontaneous speech sample. All tasks described show a clear developmental trend, a clear separation between the performance of typically developing and language-impaired children, and no performance differences between African American English- and Mainstream American English-speaking children.

  5. Reinforcing concomitants of electrically elicited vocalizations.

    PubMed

    Jürgens, U

    1976-09-24

    In 38 squirrel monkeys 251 vocalization-producing electrode positions were tested for their positive and negative reinforcing properties. Two groups of vocalization-producing brain areas could be distinguished: One group in which the electrically elicited vocalization was independent of the accompanying reinforcement effect, and a second group in which vocalization and reinforcement effect were correlated. The first group included the anterior cingulate gyrus, the adjacent supplementary motor area, gyrus rectus, ventromedial edge of the capsula interna, caudal periaqueductal gray and adjacent parabrachial region. The second group consited of the caudatum, septum, substantia innominata, amygdala, inferior thalamic peduncle, stria terminalis, midline thalamus, ventral and periventricular hypothalamus, substantia nigra, rostral periaqueductal gray, dorsolateral midbrain tegmentum and lateral medulla. It is hypothesized that the first group contains predominantly or exclusively "primary" vocalization substrates; the second group is thought to be composed mainly of structures whose stimulation yields vocalization secondarily due to stimulus induced motivational changes.

  6. Bayesian markets to elicit private information

    PubMed Central

    2017-01-01

    Financial markets reveal what investors think about the future, and prediction markets are used to forecast election results. Could markets also encourage people to reveal private information, such as subjective judgments (e.g., “Are you satisfied with your life?”) or unverifiable facts? This paper shows how to design such markets, called Bayesian markets. People trade an asset whose value represents the proportion of affirmative answers to a question. Their trading position then reveals their own answer to the question. The results of this paper are based on a Bayesian setup in which people use their private information (their “type”) as a signal. Hence, beliefs about others’ types are correlated with one’s own type. Bayesian markets transform this correlation into a mechanism that rewards truth telling. These markets avoid two complications of alternative methods: they need no knowledge of prior information and no elicitation of metabeliefs regarding others’ signals. PMID:28696293

  7. Cellular requirements for cutaneous sensitivity elicitation.

    PubMed

    Aoki, I

    1985-01-01

    The role of glass-adherent cells in cutaneous sensitivity (CS) elicitation has been analyzed in this study. CS responses have been revealed to be mediated by at least two distinct subsets of genetically restricted T cells: I-restricted 'DTH-like' T cells and K/D-restricted 'CTL-like' T cells. Both T-cell responses require I-A-positive glass-adherent cell populations, which lack T-cell markers, to manifest their activities. The role of the adherent cells is different in the 'DTH-like' responses and the 'CTL-like' responses. The disparities between the present results and previous contentions are discussed in this paper.

  8. WITHDRAWN: Prostaglandins for prelabour rupture of membranes at or near term.

    PubMed

    Tan, B P; Hannah, M E

    2007-07-18

    Induction of labour after prelabour rupture of membranes may reduce the risk of neonatal infection. However an expectant approach may be less likely to result in caesarean section. The objective of this review was to assess the effects of induction of labour with prostaglandins versus expectant management for prelabour rupture of membranes at or near term. We searched the Cochrane Pregnancy and Childbirth Group trials register. Randomised and quasi-randomised trials comparing early use of prostaglandins (with or without oxytocin) with no early use of prostaglandins in women with spontaneous rupture of membranes before labour, and 34 weeks or more of gestation. Trials were assessed for quality and data were abstracted. Fifteen trials were included. Most were of moderate to good quality. Different forms of prostaglandin preparations were used in these trials and it may be inappropriate to combine their results. Induction of labour by prostaglandins was associated with a decreased risk of chorioamnionitis (odds ratio 0.77, 95% confidence interval 0.61 to 0.97) based on eight trials and admission to neonatal intensive care (odds ratio 0.79, 95% confidence interval 0.66 to 0.94) based on seven trials. No difference was detected for rate of caesarean section, although induction by prostaglandins was associated with a more frequent maternal diarrhoea and use of anaesthesia and/or analgesia. Based on one trial, women were more likely to view their care positively if labour was induced with prostaglandins,. Induction of labour with prostaglandins appears to decrease the risk of maternal infection (chorioamnionitis) and admission to neonatal intensive care. Induction of labour with prostaglandins does not appear to increase the rate of caesarean section, although it is associated with more frequent maternal diarrhoea and pain relief.

  9. Biosynthesis of prostaglandins in gingiva of patients with chronic periodontitis

    SciTech Connect

    Mendieta, C.F.; Reeve, C.M.; Romero, J.C.

    1985-01-01

    This study was undertaken to determine the ability of inflamed and normal gingival tissues to synthesize prostaglandins (PGs) from the precursor arachidonic acid. Thirteen samples of inflamed human gingival tissue and six samples of normal human gingival tissue were studied. The inflammation was characterized histologically. After incubation of the tissue with (/sup 14/C)arachidonate, PG metabolites were separated by thin-layer chromatography and identified by comparison with co-chromatographed standards. Inflamed gingival tissue synthesized significantly larger amounts, compared to normal tissue, of 6-keto-PGF1 alpha (P less than 0.05), thromboxane B2, PGD2, and PGA2. Some unidentified metabolites, possibly lipoxygenase products were detected in significantly larger amounts in inflamed than in normal tissue.

  10. Prostaglandin inhibitor and radiotherapy in advanced head and neck cancers

    SciTech Connect

    Pillsbury, H.C. III; Webster, W.P.; Rosenman, J.

    1986-05-01

    Radiotherapy is the usual mode of treatment for unresectable head and neck cancer. To improve cure rates, extend survival, and reduce morbidity, we use accelerated hyperfractionation radiotherapy and an adjuvant drug to inhibit prostaglandin synthesis. In this study, 19 patients received 300 rad/day of radiotherapy in two equally divided doses to a total dose averaging 6,200 rad. Either indomethacin, 25 mg, or placebo was given four times a day in a double-blind fashion during therapy. Radiation mucositis was graded as 0 to 4+; pain, nutritional status, and tumor status were monitored daily and recorded biweekly. Evaluation of the data showed delayed mucositis in the experimental group for grades 1 to 3, with a significant difference at grade 3 compared with controls. The significance of a long-term comparison of cure rates would be doubtful considering the heterogeneity of the primary sites and regional disease in this group coupled with the small size of our study.

  11. Prostaglandins. A review of neurophysiology and psychiatric implications.

    PubMed

    Gross, H A; Dunner, D L; Lafleur, D; Meltzer, H L; Muhlbauer, H L; Fieve, R R

    1977-10-01

    This article reviews the function of prostaglandins (PGs) in the nervous system and discusses the possible alterations in PG metabolism as relating to mental illness. The PGs are a unique group of cyclic fatty acids whose immediate precursors are thought to function postsynaptically by inhibition or facillitation of neurotransmission through cyclase inhibition or activation, and by means of a negative feedback loop to inhibit further release of neurotransmitter from the presynaptic nerve. A review of PGs in psychiatric conditions is presented as well as a discussion of the interaction of psychoactive drugs with the PGs. The concluding section of this review discusses possible future strategies to provide insight into PG physiology as it relates to synaptic transmission in normal and pathological conditions in man.

  12. Local prostaglandin administration for mid trimester abortion: a retrospective analysis.

    PubMed

    Cameron, I T; Baird, D T

    1987-01-01

    The hospital records of 548 consecutive patients undergoing midtrimester pregnancy termination by the local administration of prostaglandins (PGs) have been reviewed. Most women (352 or 64%) were single and 322 (59%) were pregnant for the 1st time. 2/3 of the patients (361 or 66%) were between 12-16 weeks pregnant, whereas 7 (1%) were considered to be more than 20 weeks pregnant. In 401 cases (92%), abortion was performed under Item 2 of the 1967 Abortion Act, although Item 4 was cited in 34 (81%) of those individuals with a pregnancy of greater than 17 weeks duration. Apart from 10 women (2%) in whom severe hemorrhage was documented, the major complication rate was less than 1%. The use of local PGs provides a safe, effective treatment method for therapeutic abortion in the 2nd trimester.

  13. [COX-2 regulation of prostaglandins in synaptic signaling].

    PubMed

    Yang, Hong-Wei

    2009-10-01

    Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme converting arachidonic acid to prostaglandins (PGs), which is a key messenger in traumatic brain injury- and ischemia-induced neuronal damage and in neuroinflammation. COX-2 is implicated in the pathogeneses of neurodegenerative diseases. Growing evidence implies that the contribution of COX-2 to neuropathology is associated with its involvement in synaptic alteration. Elevation or inhibition of COX-2 has been shown to enhance or suppress excitatory glutamatergic neurotransmission and long-term potentiation (LTP). These events are mainly mediated via PGE2, the predominant reaction product of COX-2, and the PGE2 subtype 2 receptor (EP2). Thus, elucidation of COX-2 in synaptic signaling may provide a mechanistic basis for designing new drugs aimed at preventing, treating or alleviating neuroinflammation-associated neurological disorders.

  14. Concentration of prostaglandins in seminal fluid of fertile men.

    PubMed

    Bendvold, E; Gottlieb, C; Svanborg, K; Bygdeman, M; Eneroth, P

    1987-04-01

    Semen samples from 31 men, all of whom had fathered a child within the preceding year, were analysed for sperm characteristics and for the content of prostaglandins (PGs). Mean concentrations (mg/l) for the four main groups of PGs were 67.1 for PGE, 3.2 for PGF, 245.7 for 19-hydroxy-PGE and 13.3 for 19-hydroxy-PGF. The individual values were distributed over a relatively wide range but the extremely wide ranges reported by previous authors were not confirmed. Information is also presented concerning the relative proportions of the four isomers of PGF, as well as those of 19-hydroxy-PGF. Only sperm density was related to PG concentration in fertile men. Polyzoospermia was associated with a low PGE concentration.

  15. Human semen prostaglandins do not affect sperm motility and migration.

    PubMed

    Procaccini, J C; Gimeno, M F; Kesserü, E; Asch, R H

    1985-01-01

    Prostaglandin (PG) E2, PGF2 alpha and testosterone (T) concentrations were determined in the seminal plasma of 57 fertility-clinic patients. Results (mean less than SE) were: PGE2, 3.44 +/- 0.38 mu/ml; PGF2 alpha, 138 +/- 0.33 micrograms/ml; T, 429.54 +/- 14.01 pg/ml. The material was divided into 4 groups: normospermic, oligozoospermic, asthenozoospermic and azoospermic. No statistically significant differences were found among the values of the different groups, except for PGE2, which was found to be increased in the asthenozoospermic group. Sperm migration patterns were assessed in each semen sample, using the Kremer capillary tube test and human cervical mucus. Considering each semen sample individually, no correlations whatever were found among sperm count, motility and migration parameters and the respective concentrations of both PGs and T, nor was there a correlation among PGE2, PGF2 alpha, and T values of the same sample.

  16. High performance liquid chromotography of prostaglandins: biological applications.

    PubMed

    Carr, K; Sweetman, B J; Frölich, J C

    1976-01-01

    Two procedures are described for separation and purification of prostaglandins by high performance liquid chromatography. Both systems show excellent resolution of PGA2, PGE2 and PGF2a. Peak definition on the micro-particle silicic acid system is particularly good with the PGs appearing in 2-3 ml of organs effluent. Studies on reproducibility showed that PGE2 and PGE2a could be recovered with a retention volume of 54.2+/-0.76 ml and 64+/-0.6 ml, respectively (n=7, mean +/-50) with good recovery. The column can be run in about one hour and can be regenerated indefinitely (greater than 200 times). The degree of purification is compatible with analysis by gas chromatography-mass spectrometry. Examples showing the application of this chromatographic method to human seminal fluid, human renal tissue, platelet rich plasma and human urine samples indicate that it makes possible analysis of these samples even at low levels.

  17. The use of prostaglandin pessaries prior to vaginal termination.

    PubMed

    Craft, I

    1973-03-01

    Prosaglandin F2alpha 100 mg pessaries were inserted on 2 occasions within 24 hours of vaginal termination of pregnancy in an attempt to facilitate the subsequent operative procedure. Some degree of cervical dilatation occurred in 8 out of the 10 subjects studied but in only multiparous patients was it of sufficient degree to make evacuation easier. Side effects of uterine cramps, a flushed sensation; and the presence of diarrhea were relatively common. Disadvantages of prostaglandin F2a pessaries for use in vaginal termination of pre.g.nancy (e.g., large amounts are needed to induce cervical dilatation; cervical trauma is affected by parity status, no local specific ccervical softening action) preclude its clinical use.

  18. Temperature regulation and prostaglandin E1 fever in scorpions.

    PubMed Central

    Cabanac, M; Le Guelte, L

    1980-01-01

    1. Scorpions Buthus occitanus and Androctonus australis were placed in a temperature gradient where they could select their thermopreferendum. Intrathoracic temperature was recorded continuously. 2. Both species selected 24.8 +/- 1.0 degrees C as their preferred body temperature. No nycthemeral cycle of preference was observed in the experimental conditions. Saline injection did not modify this thermopreferendum. 3. Prostaglandin E1 (PGE1) produced a fever. Duration and magnitude of fevers were related to PGE1 doses in a bell-shaped curve. The longest and highest fevers were obtained with 4 microgram . g-1 PGE1. 4. These results show that there is an ability to produce fever and, thus, indirectly, that there is a set point in body temperature regulation in arthropods, among the oldest known terrestrial animals. PMID:7431238

  19. Prostaglandin Pathway Gene Therapy for Sustained Reduction of Intraocular Pressure

    PubMed Central

    Barraza, Román A; McLaren, Jay W; Poeschla, Eric M

    2009-01-01

    Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in prostaglandin (PG) biosynthesis. In the eye, loss of COX-2 expression in aqueous humor–secreting cells has been associated with primary open-angle glaucoma (POAG). Reduction of intraocular pressure (IOP) is the main treatment goal in this disease. We used lentiviral vectors to stably express COX-2 and other PG biosynthesis and response transgenes in the ciliary body epithelium and trabecular meshwork (TM), the ocular suborgans that produce aqueous humor and regulate its outflow, respectively. We show that robust ectopic COX-2 expression and PG production require COX-2 complementary DNA (cDNA) sequence optimization. When COX-2 expression was coupled with a similarly optimized synthetic PGF2α receptor transgene to enable downstream signaling, gene therapy produced substantial and sustained reductions in IOP in a large animal model, the domestic cat. This study provides the first gene therapy for correcting the main cause of glaucoma. PMID:19953083

  20. Effect of flunixin meglumine on prostaglandin F2 alpha synthesis and metabolism in the pig.

    PubMed

    Odensvik, K; Cort, N; Basu, S; Kindahl, H

    1989-09-01

    The effect of flunixin meglumine on prostaglandin synthesis and metabolism was evaluated in the pig in vivo. It was found that the prostaglandin metabolite, 15-ketodihydro-PGF2 alpha, was decreased in the peripheral circulation within 20 min of injection of the drug. In therapeutic doses in the pig the drug had no effect on the metabolism of PGF2 alpha. Flunixin was compared with some other non-steroidal anti-inflammatory drugs in an in vitro test system utilizing sheep vesicular gland microsomes. It was concluded that this drug is a potent inhibitor of prostaglandin synthesis.

  1. Intravesical prostaglandin F2 for promoting bladder emptying after surgery for female stress incontinence.

    PubMed

    Tammela, T; Kontturi, M; Käär, K; Lukkarinen, O

    1987-07-01

    Prostaglandin F2 alpha 10 mg was administered intravesically in a double-blind placebo-controlled study to promote micturition in cases of urinary retention after operative treatment of urinary stress incontinence in women. Fifteen of 18 patients (83%) succeeded in voiding after treatment with prostaglandin F2 alpha, but the placebo was ineffective in all 18 patients (P less than 0.001). Although the effect of prostaglandin F2 alpha on bladder muscle contraction was short-lived, it seemed to enhance the restoration of bladder motor function with no serious side effects, and thus to be clinically useful in the treatment of post-operative urinary retention.

  2. Involvement of endogenous prostaglandins in ischemic preconditioning in pigs.

    PubMed

    Gres, Petra; Schulz, Rainer; Jansen, Johanna; Umschlag, Christian; Heusch, Gerd

    2002-08-15

    In pigs, the infarct size (IS) reduction achieved by a strong preconditioning stimulus (IPs) of 10 min ischemia and 15 min reperfusion is greater than that by a weaker preconditioning stimulus (IPw) of 3 min ischemia and 15 min reperfusion. The cardioprotection achieved by IPw is completely abolished by blockade of bradykinin-B(2)-receptors. Since activation of bradykinin-B(2)-receptors subsequently activates cyclooxygenase, we now tested whether or not inhibition of cyclooxygenase with indomethacin interferes with IS reduction by IP. In 42 enflurane-anesthetized pigs, the LAD coronary artery was cannulated, and subendocardial blood flow (ENDO, microspheres, ml/min/g) and IS (%, TTC-staining) were determined. Following 90 min ischemia and 120 min reperfusion, IS averaged 25.5+/-3.8 (S.E.M.) (ENDO: 0.05+/-0.01). IS was reduced by IPw to 6.3+/-2.1 (ENDO: 0.07+/-0.01) and further reduced by IPs to 2.4+/-1.0 (ENDO: 0.06+/-0.01). Indomethacin (10 mg/kg i.v.) did not alter IS per se (20.9+/-5.4, ENDO: 0.06+/-0.02), but completely abolished the IS reduction by IPw (23.2+/-5.9, ENDO: 0.06+/-0.01). In contrast, indomethacin abolished the IS reduction by IPs in only two of seven pigs (16.1+/-7.4, ENDO: 0.05+/-0.01). Prostaglandins are involved in IP. However, with stronger IP stimuli other triggers/mediators can compensate for the lack of prostaglandins.

  3. Fetal placental prostaglandin metabolism in the peripartum cow

    SciTech Connect

    Gross, T.S.; Williams, W.F.; Lewis, G.S.

    1986-03-05

    Previous results demonstrate that fetal placental tissue synthesizes prostaglandin E (PGE) prior to parturition. When placental membranes do not separate postpartum, PGE synthesis is maintained, while prostaglandin F (PGF) synthesis predominates when the membranes separate. Concurrent with separation is a decline in fetal placental binucleate cell (BNC) numbers. These data suggest a fetal placental conversion of PGE to PGF. For this experiment, placentomes were collected at ten days prepartum (PRE, n=12) and within 1 hr postpartum. Nine of the postpartum animals had fetal membrane separation within 12 hr postpartum (S) and eight did not exhibit membrane separation (NS). For each placentome, fetal (villi) components were manually isolated and examined for the ability to interconvert /sup 3/H labeled PGE/sub 2/ and PGF/sub 2/. All villi were unable to convert PGE/sub 2/ to PGF/sub 2/ (P > .05). The PRE and NS villi were able to convert PGF/sub 2/ to PGE/sub 2/ (P < .05) while S villi could not. When the BNC decline in numbers, as in the S villi, the ability to convert PGF/sub 2/ to PGE/sub 2/ (P < .05) while S villi could not. When the BNC decline in numbers, as in the S villi, the ability to convert PGF/sub 2/ to PGE/sub 2/ also declines (P < .05). These data suggest that peripartum fetal placental tissue might synthesize PGF which is then converted to PGE. It is possible that the BNC are directly converting PGF to PGE or that they are modulating this conversion. Therefore, with a decline in BNC numbers, PGF synthesis would predominate.

  4. Prostaglandin endoperoxide H synthases: peroxidase hydroperoxide specificity and cyclooxygenase activation.

    PubMed

    Liu, Jiayan; Seibold, Steve A; Rieke, Caroline J; Song, Inseok; Cukier, Robert I; Smith, William L

    2007-06-22

    The cyclooxygenase (COX) activity of prostaglandin endoperoxide H synthases (PGHSs) converts arachidonic acid and O2 to prostaglandin G2 (PGG2). PGHS peroxidase (POX) activity reduces PGG2 to PGH2. The first step in POX catalysis is formation of an oxyferryl heme radical cation (Compound I), which undergoes intramolecular electron transfer forming Intermediate II having an oxyferryl heme and a Tyr-385 radical required for COX catalysis. PGHS POX catalyzes heterolytic cleavage of primary and secondary hydroperoxides much more readily than H2O2, but the basis for this specificity has been unresolved. Several large amino acids form a hydrophobic "dome" over part of the heme, but when these residues were mutated to alanines there was little effect on Compound I formation from H2O2 or 15-hydroperoxyeicosatetraenoic acid, a surrogate substrate for PGG2. Ab initio calculations of heterolytic bond dissociation energies of the peroxyl groups of small peroxides indicated that they are almost the same. Molecular Dynamics simulations suggest that PGG2 binds the POX site through a peroxyl-iron bond, a hydrogen bond with His-207 and van der Waals interactions involving methylene groups adjoining the carbon bearing the peroxyl group and the protoporphyrin IX. We speculate that these latter interactions, which are not possible with H2O2, are major contributors to PGHS POX specificity. The distal Gln-203 four residues removed from His-207 have been thought to be essential for Compound I formation. However, Q203V PGHS-1 and PGHS-2 mutants catalyzed heterolytic cleavage of peroxides and exhibited native COX activity. PGHSs are homodimers with each monomer having a POX site and COX site. Cross-talk occurs between the COX sites of adjoining monomers. However, no cross-talk between the POX and COX sites of monomers was detected in a PGHS-2 heterodimer comprised of a Q203R monomer having an inactive POX site and a G533A monomer with an inactive COX site.

  5. Vasopressin-induced natriuresis in the conscious rat: role of blood pressure, renal prostaglandin synthesis and the peptide ANF.

    PubMed Central

    Lote, C J; Thewles, A; Wood, J A

    1989-01-01

    1. The response to arginine vasopressin (AVP) at doses of 5 and 10 pmol (100 g body weight)-1 h-1 was studied in conscious rats during the infusion of 1% (w/v) dextrose at 11.6 ml h-1 with and without pre-treatment with indomethacin. 2. In the absence of indomethacin AVP infusion induced dose-related increases in sodium output that were positively correlated with increases in mean arterial blood pressure (MAP) and plasma atrial natriuretic factor (ANF) immunoreactivity. Increases in renal prostaglandin E2 (PGE2) synthesis were also associated with AVP infusion. 3. Indomethacin pre-treatment abolished the AVP-induced increases in renal PGE2 synthesis and also the dose-related differences in ANF immunoreactivity. Increases in MAP and sodium output were unaffected at the 10 pmol (100 g body weight)-1 h-1 dose of AVP and only slightly attenuated for the 5 pmol (100 g body weight)-1 h-1 dose. 4. For both series AVP induced marked falls in glomerular filtration rate (GFR) but only small transient falls in effective renal plasma flow. The observed falls in GFR support the view that the natriuresis is due to changes in tubular handling and not in the filtered load of sodium. 5. It is concluded that the natriuresis elicited by AVP is closely related to the pressor action of the hormone but renal PGE2 synthesis and plasma ANF are not responsible for mediating this response. PMID:2533261

  6. Involvement of PPARgamma in oxidative stress-mediated prostaglandin E(2) production in SZ95 human sebaceous gland cells.

    PubMed

    Zhang, Qiwei; Seltmann, Holger; Zouboulis, Christos C; Konger, Raymond L

    2006-01-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma) is thought to play a role in sebaceous gland cell function. We previously demonstrated in human epidermoid carcinoma KB cells that UVB irradiation activates PPARgamma via the generation of multiple oxidized glycerophosphocholine species with PPARgamma ligand activity. UVB-induced cyclooxygenase 2 (COX-2) expression was also shown to be PPARgamma-dependent. We therefore reasoned that PPARgamma activation and PPARgamma-dependent COX-2 expression may occur as a general consequence of oxidative stress. The present studies were designed to examine the effects of the oxidant tert-butylhydroperoxide (TBH) on PPARgamma activation and COX-2 expression in SZ95 sebocytes. We first verified that functional PPARgamma is expressed and activated by UVB irradiation in these cells. We next demonstrated that TBH increased PPARgamma reporter activity in SZ95 sebocytes. Increased COX-2 protein, mRNA expression, and prostaglandin E(2) (PGE(2)) production was observed after TBH or PPARgamma agonist treatment. The ability of PPARgamma agonists and TBH to induce COX-2 expression and PGE(2) production was blocked by pretreatment with the specific PPARgamma antagonist GW9662. Finally, TBH and PPARgamma agonists failed to elicit a PGE(2) response in SZ95 sebocytes stably expressing a dominant-negative PPARgamma. This study illustrates the importance of the PPARgamma system in regulating cellular responses to oxidative stress.

  7. Serelaxin Elicits Bronchodilation and Enhances β-Adrenoceptor-Mediated Airway Relaxation

    PubMed Central

    Lam, Maggie; Royce, Simon G.; Donovan, Chantal; Jelinic, Maria; Parry, Laura J.; Samuel, Chrishan S.; Bourke, Jane E.

    2016-01-01

    Treatment with β-adrenoceptor agonists does not fully overcome the symptoms associated with severe asthma. Serelaxin elicits potent uterine and vascular relaxation via its cognate receptor, RXFP1, and nitric oxide (NO) signaling, and is being clinically evaluated for the treatment of acute heart failure. However, its direct bronchodilator efficacy has yet to be explored. Tracheal rings were prepared from male Sprague-Dawley rats (250–350 g) and tricolor guinea pigs, and precision cut lung slices (PCLSs) containing intrapulmonary airways were prepared from rats only. Recombinant human serelaxin (rhRLX) alone and in combination with rosiglitazone (PPARγ agonist; recently described as a novel dilator) or β-adrenoceptor agonists (isoprenaline, salbutamol) were added either to pre-contracted airways, or before contraction with methacholine or endothelin-1. Regulation of rhRLX responses by epithelial removal, indomethacin (cyclooxygenase inhibitor), L-NAME (nitric oxide synthase inhibitor), SQ22536 (adenylate cyclase inhibitor) and ODQ (guanylate cyclase inhibitor) were also evaluated. Immunohistochemistry was used to localize RXFP1 to airway epithelium and smooth muscle. rhRLX elicited relaxation in rat trachea and PCLS, more slowly than rosiglitazone or isoprenaline, but potentiated relaxation to both these dilators. It markedly increased β-adrenoceptor agonist potency in guinea pig trachea. rhRLX, rosiglitazone, and isoprenaline pretreatment also inhibited the development of rat tracheal contraction. Bronchoprotection by rhRLX increased with longer pre-incubation time, and was partially reduced by epithelial removal, indomethacin and/or L-NAME. SQ22536 and ODQ also partially inhibited rhRLX-mediated relaxation in both intact and epithelial-denuded trachea. RXFP1 expression in the airways was at higher levels in epithelium than smooth muscle. In summary, rhRLX elicits large and small airway relaxation via epithelial-dependent and -independent mechanisms, likely

  8. Production of prostaglandins by the pseudopregnant rat uterus, in vitro, and the effect of tamoxifen with the identification of 6-keto-prostaglandin F1alpha as a major product.

    PubMed Central

    Fenwick, L; Jones, R L; Naylor, B; Poyser, N L; Wilson, N H

    1977-01-01

    1 Prostaglandin production by rat uterus homogenates has been studied, in vitro, on days 2 to 13 of pseudopregnancy. 2 The highest production of prostaglandins occurred on day 5. 3 The amounts of prostaglandins F and D formed were higher than the amounts of prostaglandin E on every day studied. 4 The ratios of prostglandins F and D to prostaglandin E produced steadily decreased up to day 6. It then increased with the highest values occurring between days 10 and 13, 5 Progesterone levels in peripheral plasma increased rapidly from days 2 to 5, remained high up to day 9, then steadily decreased between days 10 and 13. 6 The anti-oestrogenic drug, tamoxifen administered on day 2, significantly inhibited the increase of prostaglandin production which occurred on day 5. Prostaglandin E production was inhibited more than the production of prostaglandins F and D. 7 Analysis of the uterine extracts by gas chromatography and mass spectrometry showed prostaglandin F2alpha, F1alpha (in trace amounts), E2 and D2 to be present. 8 The major product detected was 6-keto-prostaglandin F1alpha. Its identification forms an addendum to the paper. 9 Also present as a major product was 6(9)-oxy-11,15-dihydroxyprosta-7,13-dienoic acid. PMID:836998

  9. Testosterone induction of prostaglandin-endoperoxide synthase 2 expression and prostaglandin F(2alpha) production in hamster Leydig cells.

    PubMed

    Matzkin, María E; Gonzalez-Calvar, Silvia I; Mayerhofer, Artur; Calandra, Ricardo S; Frungieri, Mónica B

    2009-07-01

    We have previously observed expression of prostaglandin-endoperoxide synthase 2 (PTGS2), the key enzyme in the biosynthesis of prostaglandins (PGs), in reproductively active Syrian hamster Leydig cells, and reported an inhibitory role of PGF(2alpha) on hamster testicular steroidogenesis. In this study, we further investigated PTGS2 expression in hamster Leydig cells during sexual development and photoperiodic gonadal regression. Since PTGS2 is mostly expressed in pubertal and reproductively active adult hamsters with high circulating levels of LH and androgens, we studied the role of these hormones in the regulation/maintenance of testicular PTGS2/PGF(2alpha). In active hamster Leydig cells, LH/hCG and testosterone induced PTGS2 and PGF(2alpha) production, and their actions were abolished by the antiandrogen bicalutamide (Bi). These results indicate that LH does not exert a direct effect on PG synthesis. Testosterone also stimulated phosphorylation of the mitogen-activated protein kinase isoforms 3/1 (MAPK3/1) within minutes and hours, but the testosterone metabolite dihydrotestosterone had no effect on PTGS2 and MAPK3/1. Because Bi and U0126, an inhibitor of the MAP kinase kinases 1 and 2 (MAP2K1/2), abolished testosterone actions on MAPK3/1 and PTGS2, our studies suggest that testosterone directly induces PTGS2/PGF(2alpha) in hamster Leydig cells via androgen receptors and a non-classical mechanism that involves MAPK3/1 activation. Since PGF(2alpha) inhibits testosterone production, it might imply the existence of a regulatory loop that is setting a brake on steroidogenesis. Thus, the androgen environment might be crucial for the regulation of testicular PG production at least during sexual development and photoperiodic variations in hamsters.

  10. Peroxidative oxidation of leuco-dichlorofluorescein by prostaglandin H synthase in prostaglandin biosynthesis from polyunsaturated fatty acids.

    PubMed

    Larsen, L N; Dahl, E; Bremer, J

    1996-01-05

    Prostaglandin H synthase can oxidize arachidonic acid with leuco-dichlorofluorescein as reducing cosubstrate. Addition of 0.5 mM phenol increases the oxidation of leuco-dichlorofluorescein to dichlorofluorescein 5-fold, probably by acting as a cyclic intermediate in the oxidation. Tetramethyl-p-phenylenediamine is also oxidized as cosubstrate. Its oxidation is not influenced by phenol. A stoichiometry of close to one mole of tetramethyl-p-phenylenediamine or leuco-dichlorofluorescein consumed per mole of arachidonic acid was found in the initial phase of the reaction. In the presence of phenol + leuco-dichlorofluorescein, the oxidation rate of arachidonic acid is about 40% lower than with phenol alone as cosubstrate. Since dichlorofluorescein has a molar extinction coefficient of 91 . 10(3) at 502 nm, the oxidation of less than 1 microM leuco-dichlorofluorescein can be detected spectrophotometrically. The rate of extinction change with leuco-dichlorofluorescein (at 502 nm) is about 4-fold more rapid than with tetramethyl-p-phenylenediamine (at 611 nm). With this spectrophotometric assay we have confirmed that arachidonic acid, linolenic acid, adrenic acid, gamma-linolenic acid, eicosapentaenoic acid, are substrates for prostaglandin H synthase with decreasing reaction rates in the mentioned order. The same order of reaction rates were found when oxygen consumption was measured. The assay also shows that docosahexaenoic acid is substrate for the enzyme. The reaction rate of the enzyme evidently is decreased both by a n-3 double bond and by deviation from a 20 carbon chain length of the fatty acid substrate.

  11. Expert Elicitation of Population-Level Effects of Disturbance.

    PubMed

    Fleishman, Erica; Burgman, Mark; Runge, Michael C; Schick, Robert S; Kraus, Scott

    2016-01-01

    Expert elicitation is a rigorous method for synthesizing expert knowledge to inform decision making and is reliable and practical when field data are limited. We evaluated the feasibility of applying expert elicitation to estimate population-level effects of disturbance on marine mammals. Diverse experts estimated parameters related to mortality and sublethal injury of North Atlantic right whales (Eubalaena glacialis). We are now eliciting expert knowledge on the movement of right whales among geographic regions to parameterize a spatial model of health. Expert elicitation complements methods such as simulation models or extrapolations from other species, sometimes with greater accuracy and less uncertainty.

  12. Web-based tool for expert elicitation of the variogram

    NASA Astrophysics Data System (ADS)

    Truong, Phuong N.; Heuvelink, Gerard B. M.; Gosling, John Paul

    2013-02-01

    The variogram is the keystone of geostatistics. Estimation of the variogram is deficient and difficult when there are no or too few observations available due to budget constraints or physical and temporal obstacles. In such cases, expert knowledge can be an important source of information. Expert knowledge can also fulfil the increasing demand for an a priori variogram in Bayesian geostatistics and spatial sampling optimization. Formal expert elicitation provides a sound scientific basis to reliably and consistently extract knowledge from experts. In this study, we aimed at applying existing statistical expert elicitation techniques to extract the variogram of a regionalized variable that is assumed to have either a multivariate normal or lognormal spatial probability distribution from expert knowledge. To achieve this, we developed an elicitation protocol and implemented it as a web-based tool to facilitate the elicitation of beliefs from multiple experts. Our protocol has two main rounds: elicitation of the marginal probability distribution and elicitation of the variogram. The web-based tool has three main components: a web interface for expert elicitation and feedback; a component for statistical computation and mathematical pooling of multiple experts' knowledge; and a database management component. Results from a test case study show that the protocol is adequate and that the online elicitation tool functions satisfactorily. The web-based tool is free to use and supports scientists to conveniently elicit the variogram of spatial random variables from experts. The source code is available from the journal FTP site under the GNU General Public License.

  13. Expert elicitation of population-level effects of disturbance

    USGS Publications Warehouse

    Fleishman, Erica; Burgman, Mark; Runge, Michael C.; Schick, Robert S; Krauss, Scott; Popper, Arthur N.; Hawkins, Anthony

    2016-01-01

    Expert elicitation is a rigorous method for synthesizing expert knowledge to inform decision making and is reliable and practical when field data are limited. We evaluated the feasibility of applying expert elicitation to estimate population-level effects of disturbance on marine mammals. Diverse experts estimated parameters related to mortality and sublethal injury of North Atlantic right whales (Eubalaena glacialis). We are now eliciting expert knowledge on the movement of right whales among geographic regions to parameterize a spatial model of health. Expert elicitation complements methods such as simulation models or extrapolations from other species, sometimes with greater accuracy and less uncertainty.

  14. Role of mucosal prostaglandins and DNA synthesis in gastric cytoprotection by luminal epidermal growth factor.

    PubMed Central

    Konturek, S J; Brzozowski, T; Piastucki, I; Dembinski, A; Radecki, T; Dembinska-Kiec, A; Zmuda, A; Gregory, H

    1981-01-01

    This study compares the effect of epidermal growth factor and prostaglandins (PGE2 or PGI2), applied topically to gastric mucosa, on gastric secretion and formation of ASA-induced gastric ulcerations in rats. Epidermal growth factor given topically in non-antisecretory doses prevented dose-dependently the formation of ASA-induced ulcers without affecting prostaglandin generation but with a significant rise in DNA synthesis in the oxyntic mucosa. The anti-ulcer effect of topical prostaglandins was also accompanied by an increase in DNA synthesis. This study indicates that topical epidermal growth factor, like PGE2 or PGI2, is cytoprotective and that this cytoprotection is not mediated by the inhibition of gastric secretion or prostaglandin formation but related to the increase in DNA synthesis in oxyntic mucosa. PMID:7030877

  15. Celecoxib improves host defense through prostaglandin inhibition during Histoplasma capsulatum infection.

    PubMed

    Pereira, Priscilla Aparecida Tartari; Trindade, Bruno Caetano; Secatto, Adriana; Nicolete, Roberto; Peres-Buzalaf, Camila; Ramos, Simone Gusmão; Sadikot, Ruxana; Bitencourt, Claudia da Silva; Faccioli, Lúcia Helena

    2013-01-01

    Prostaglandins act as mediators of inflammation and, similar to cytokines, function as immune modulators during innate and adaptive immune responses. Therefore, using a pharmacological inhibitor, celecoxib, we investigated the role of prostaglandins in host defense against Histoplasma capsulatum infection in C57BL/6 mice. Our results showed that treatment with celecoxib inhibited cyclooxygenase 2, reduced the total fungal burden, and reduced the concentration of PGE2, cytokines, lymphocytes, neutrophils, and mononuclear cells in the bronchoalveolar space and lung parenchyma. In addition, celecoxib treatment increased the synthesis of nitric oxide, IFN- γ, LTB4, and the phagocytic capacity of alveolar macrophages. Moreover, celecoxib treatment increased the survival of mice after infection with a lethal inoculum of H. capsulatum. These results suggest that prostaglandins alter the host immune response and play an important role in the pathogenesis of histoplasmosis. Thus, the inhibition of prostaglandins could be a valuable immunomodulatory strategy and antifungal therapy for histoplasmosis treatment.

  16. Determination of prostaglandin analogs in cosmetic products by high performance liquid chromatography with tandem mass spectrometry.

    PubMed

    Wittenberg, James B; Zhou, Wanlong; Wang, Perry G; Krynitsky, Alexander J

    2014-09-12

    A method was developed and validated for the determination of 16 prostaglandin analogs in cosmetic products. The QuEChERS (Quick, Easy, Cheap, Efficient, Rugged, Safe) liquid-liquid extraction method, typically used for pesticide residue analysis, was utilized as the sample preparation technique. The prostaglandin analogs were chromatographically separated and quantified using high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Thirty-one cosmetic products were surveyed, and 13 products were determined to contain a prostaglandin analog with amounts ranging from 27.4 to 297μg/g. The calculated concentrations for the cosmetic products were in a similar range when compared to the concentrations of three different prostaglandin analog-containing prescription products.

  17. [Prostaglandin E1 in the treatment of chronic ischemia of the extremities].

    PubMed

    Kowal-Gierczak, B; Kurzawska-Mielecka, M; Czarnacki, M

    1990-11-01

    The authors observed the effect of prostaglandin E1 (Prostavasine) on the blood flow in the lower extremities in 25 patients with chronic ischemia caused by thrombo-angitis obliterans and arteriosclerosis obliterans (clinical stage III and IV). The blood flow in the lower extremities and the effects of prostaglandin E1 were assessed by means of rheo-angiographic and Doppler-testing investigations. The parameters A (amplitude), S (area) and WOT (index) of rheo-angiographic curves showed significant increased. No significant changes were found in the determined Doppler's indexes. The observed differences of values the parameters of rheo-angiographic curves suggests that prostaglandin E1 evident improvement the tissue blood flow in patients with critical ischemia of the lower extremities. The authors found that prostaglandin E1 was without any significant effect dilating the great vessels, but an evident improvement was observed in rheo-angiographic records which reflect rather the blood flow values in the small vessels.

  18. [The importance of oxytocin and prostaglandins to the mechanism of labor in humans].

    PubMed

    Husslein, P

    1984-01-01

    In the present work an attempt is made to get a deeper insight into the mechanism of labor and the events leading to the onset of labor by means of radioimmunological measurements of OT, PGE, PGF, PGEM and PGFM and by determining the oxytocin sensitivity and the concentration of oxytocin receptors. Prostaglandins play a major role for the mechanism of labor in labor of spontaneous onset as well as in several forms of induced labor (intravenous infusion of OT, amniotomy, local application of PGE2). The reason for this seems to be the 3 fold action of prostaglandins: stimulation of myometrial contractions, cervical softening, induction of gap junctions. Moreover prostaglandins produced in the placenta play a major role in the mechanism of placental separation and expulsion. Oxytocin seems to be of importance for the initiation of labor and the final expulsion of the fetus. Immediately before the onset of regular contractions a marked increase of oxytocin sensitivity can be demonstrated which correlates very well with an increase of oxytocin receptor concentration in the myometrium and decidua. Due to this increase in oxytocin sensitivity no rise in oxytocin plasma levels is necessary to induce labor. Apart from the induction of myometrial contractions oxytocin leads via receptors in the decidua to a stimulation of prostaglandin synthesis which can also be demonstrated in vitro. In cases of premature contractions the same mechanisms seem to be operational as at term, oxytocin and prostaglandins again playing a major role. Inhibition of contractions with ethanol is based on the capacity of alcohol to inhibit oxytocin secretion. The contractions inhibiting effect of ritodrine is mediated through the cAMP induced relaxation of the myometrium although possibly a direct reduction of prostaglandin synthesis by ritodrine is possible. Increasing estrogen and decreasing progesterone activities at term lead to multiple subtile changes leading to an increased prostaglandin

  19. Basic emotions elicited by odors and pictures.

    PubMed

    Croy, Ilona; Olgun, Selda; Joraschky, Peter

    2011-12-01

    The sense of olfaction is often reported to have a special relationship with emotional processing. Memories triggered by olfactory cues often have a very emotional load. On the other hand, basic negative or positive emotional states should be sufficient to cover the most significant functions of the olfactory system including ingestion, hazard avoidance, and social communication. Thus, we investigated whether different basic emotions can be evoked in healthy people through the sense of olfaction. We asked 119 participants which odor evokes one of the six basic emotions (happiness, disgust, anger, anxiety, sadness, and surprise); another 97 participants were asked about pictures evoking those emotions. The results showed that almost every participant could name an olfactory elicitor for happiness or disgust. Olfactory elicitors of anxiety were reported less frequently, but they were still reported by three-quarters of the participants. However, for sadness and anger only about half of the participants reported an olfactory elicitor, whereas significantly more named a visual cue. Olfactory emotion elicitors were mainly related to the classes of culture, plants, and food, and visual emotion elicitors were largely related to humans. This data supports the hypothesis that in the vast majority of people, few differentiated emotions can be elicited through the olfactory channel. These emotions are happiness, disgust, and anxiety. (c) 2011 APA, all rights reserved.

  20. Eliciting and using expert knowledge in metrology

    NASA Astrophysics Data System (ADS)

    O'Hagan, Anthony

    2014-08-01

    The expression of uncertainty has hitherto been seen as an add-on—first an estimate is obtained and then uncertainty in that estimate is evaluated. We argue that quantification of uncertainty should be an intrinsic part of measurement and that the measurement result should be a probability distribution for the measurand. Full quantification of uncertainties in measurement, recognizing and quantifying all sources of uncertainty, is rarely simple. Many potential sources of uncertainty can effectively only be quantified by the application of expert judgement. Scepticism about the validity or reliability of expert judgement has meant that these sources of uncertainty have often been overlooked, ignored or treated in a qualitative, narrative way. But the consequence of this is that reported expressions of uncertainty regularly understate the true degree of uncertainty in measurements. This article first discusses the concept of quantifying uncertainty in measurement, and then considers some of the areas where expert judgement is needed in order to quantify fully the uncertainties in measurement. The remainder of the article is devoted to describing methodology for eliciting expert knowledge.

  1. Acting green elicits a literal warm glow

    NASA Astrophysics Data System (ADS)

    Taufik, Danny; Bolderdijk, Jan Willem; Steg, Linda

    2015-01-01

    Environmental policies are often based on the assumption that people only act environmentally friendly if some extrinsic reward is implicated, usually money. We argue that people might also be motivated by intrinsic rewards: doing the right thing (such as acting environmentally friendly) elicits psychological rewards in the form of positive feelings, a phenomenon known as warm glow. Given the fact that people's psychological state may affect their thermal state, we expected that this warm glow could express itself quite literally: people who act environmentally friendly may perceive the temperature to be higher. In two studies, we found that people who learned they acted environmentally friendly perceived a higher temperature than people who learned they acted environmentally unfriendly. The underlying psychological mechanism pertains to the self-concept: learning you acted environmentally friendly signals to yourself that you are a good person. Together, our studies show that acting environmentally friendly can be psychologically rewarding, suggesting that appealing to intrinsic rewards can be an alternative way to encourage pro-environmental actions.

  2. Plasma prostaglandins across the tumor bed of patients with gynecologic malignancy.

    PubMed

    Mortel, R; Allegra, J C; Demers, L M; Harvey, H A; Trautlein, J; Nahhas, W; White, D; Gillin, M A; Lipton, A

    1977-05-01

    Prostaglandin E produced by tumors has recently been implicated as a mechanism by which tumors may subvert the immune system and grow despite their antigenicity. Arterial and venous determinations of prostaglandin E were performed in eleven patients with gynecologic malignancy. No significant difference was found when arterial and venous levels were compared and there was no difference in venous PGE levels when subjects with cancer were compared to patients with benign gynecologic disease.

  3. Prostaglandin F2alpha produced by inducible cyclooxygenase may contribute to the resolution of inflammation.

    PubMed

    Colville-Nash, Paul R; Gilroy, Derek W; Willis, Dean; Paul-Clark, Mark J; Moore, Adrian R; Willoughby, Derek A

    2005-01-01

    Cyclooxygenase-2 may play a role in resolution of carrageenan-induced pleurisy in rats by generating anti-inflammatory prostanoids. Here, we show exudate prostaglandin F2alpha concentrations rise during resolution of this model. These were reduced by the selective cyclooxygenase-2 inhibitor NS-398, which exacerbated inflammation. Concomitant treatment with NS-398 and the synthetic FP receptor agonist fluprostenol reversed this exacerbation. This suggests prostaglandin F2alpha produced by cyclooxygenase-2 contributes to resolution of this inflammatory reaction.

  4. Comparative study of antiinflammatory drugs and sulphasalazine in relation to prostaglandin E and 19 hydroxylated prostaglandin E levels and human male fertility.

    PubMed

    Freixa, R; Roselló Catafau, J; Gelpí, E; Iglesias Cortit, J L; Ballescá, J L; de Paz, J L; Iglesias Guiu, J; Gonzalez Merlo, J; Puig Parellada, P

    1984-12-01

    The effect of lysine salicylate, flurbiprofen and sulphasalazine on human seminal prostaglandin profiles of six normal individuals was studied. All of them were treated with pharmacological doses of the three agents for four days with rest periods of eighteen days in between. Sulphasalazine produced less prostaglandin (PG) inhibition relative to the other two antiinflammatory drugs but in contrast only sulphasalazine induced sperm changes. Infertility status associated with the ingestion of therapeutic levels of sulphasalaziane is not directly related to the endogenous PGEs and 19-OH PGEs, the major prostanoids in human semen. PG determinations were carried out using gas chromatographic (GC) techniques.

  5. Effects of alterations in urine flow rate on prostaglandin E excretion in conscious dogs.

    PubMed

    Kirschenbaum, M A; Serros, E R

    1980-02-01

    The relationships between urinary prostaglandin E excretion and urine flow rate were evaluated in 11 conscious mongrel dogs during antidiuresis, maximal water loading, vasopressin administration during maximal water loading, and mannitol infusion. Urine flow rates between 0.21 and 15.1 ml/min were achieved. Urinary prostaglandin E excretion rates, determined by a membrane receptor assay, varied directly with urine flow rates (r = 0.908). Vasopressin administration (34--540 microU . kg-1 . min-1) resulted in a fall, rather than the expected rise, in urinary prostaglandin E excretion. When the concentration of prostaglandin E in the urine was plotted against urine flow rate, the demonstrated relationship appeared most consistent with passive diffusion. Mannitol infusion increased urine flow rates to levels comparable to the levels seen with maximal water loading but did not result in a fall in plasma osmolality. Urinary prostaglandin E excretion rates, however, were not distinguishable from those in the previous group. These data demonstrate that urinary prostaglandin E excretion rates are determined, to a great extent, by urine flow rate and that the significance of the interpretation of elevated excretion levels of these lipids in diuretic states may have to be reevaluated.

  6. [A brief review of recent achievements concerning biochemistry and physiology of prostaglandins in the eye].

    PubMed

    Kahán, L I; Dekov, A M; Pálfalvi, M; Imre, G

    1999-11-28

    Two prostaglandin molecules have important physiological and pathophysiological role in the tissues of the eye. Prostaglandin F2 alpha takes part in mediating intraocular pressure, prostaglandin E2 is the mediator of inflammation. In case of increased intraocular pressure, latanoprost a derivative of prostaglandin F2 alpha can be applied. Numerous data are available on the favourable intraocular pressure lowering effect of latanoprost. It can be applied as a single hypotensive or it can be combined with eye-drops currently used in glaucoma. It exerts its therapeutic effect by increasing uveoscleral outflow. Inflammation in the eye can be diminished by nonsteroidal anti-inflammatory drugs similarly to inflammations in other tissues of the organism. Literature on nonsteroidal anti-inflammatory drugs is enormous. Molecules of different structures inhibit the synthesis of prostaglandins. Primarily they are useful anti-inflammatory agents, reduce intraocular pressure in secundary glaucoma, inhibit intraocular miosis and prevent development of cystoid macula oedema. Nonsteroidal anti-inflammatory drugs do not exert their effects on prostaglandins themselves, but inhibit their synthesis. Hence the use of both, latanoprost and nonsteroidal anti-inflammatory drugs simultaneously, improves safety of therapy in case of patients prone to uveitis.

  7. Signal pathways mediating oxytocin stimulation of prostaglandin synthesis in select target cells.

    PubMed

    Soloff, M S; Jeng, Y J; Copland, J A; Strakova, Z; Hoare, S

    2000-03-01

    A major action of oxytocin is to stimulate prostaglandin production in reproductive tissues. The two major enzyme systems involved are cytosolic phospholipase A2 (cPLA2), which catalyses the formation of arachidonic acid from membrane glycerophospholipids, and prostaglandin endoperoxide-H synthases-1 and -2, which allow conversion of arachidonic acid to prostaglandins. During gestation, the concentrations of all three enzymes rise in the rabbit amnion. Agonists, including oxytocin, increase cPLA2 activity, in part, by elevating intracellular Ca2+ concentration, which causes cPLA2 to be translocated from the cytosol to intracellular membrane binding sites. Cytosolic PLA2 is then activated by a mitogen-activated protein kinase (MAPK)-dependent step. Our studies have elucidated signal pathways involved in oxytocin-stimulated prostaglandin output in both rabbit amnion cells and Chinese hamster ovary cells stably transfected with the rat oxytocin receptor. The two cell types are alike with respect to oxytocin-stimulated intracellular Ca2+ transients, mediation via Gq, and the specific MAPK that catalyses the phosphorylation of cPLA2. However, they differ with respect to the mechanisms of upregulation of key enzymes involved in prostaglandin E2 synthesis. These findings illustrate the tiers of complementary mechanisms involved in oxytocin stimulation of prostaglandin E2, and the extent of the diversity in the cellular signalling pathways involved.

  8. Circadian variations of prostaglandin E2 and F2 alpha release in the golden hamster retina.

    PubMed

    de Zavalía, Nuria; Fernandez, Diego C; Sande, Pablo H; Keller Sarmiento, María I; Golombek, Diego A; Rosenstein, Ruth E; Silberman, Dafne M

    2010-02-01

    Circadian variations of prostaglandin E2 and F2alpha release were examined in the golden hamster retina. Both parameters showed significant diurnal variations with maximal values at midnight. When hamsters were placed under constant darkness for 48 h, the differences in prostaglandin release between subjective mid-day and subjective midnight persisted. Western blot analysis showed that cyclooxygenase (COX)-1 levels were significantly higher at midnight than at mid-day, and at subjective midnight than at subjective mid-day, whereas no changes in COX-2 levels were observed among these time points. Immunohistochemical studies indicated the presence of COX-1 and COX-2 in the inner (but not outer) retina. Circadian variations of retinal prostaglandin release were also assessed in suprachiasmatic nuclei (SCN)-lesioned animals. Significant differences in retinal prostaglandin release between subjective mid-day and subjective midnight were observed in SCN-lesioned animals. These results indicate that hamster retinal prostaglandin release is regulated by a retinal circadian clock independent from the SCN. Thus, the present results suggest that the prostaglandin/COX-1 system could be a retinal clock output or part of the retinal clock mechanism.

  9. DEVELOPMENT OF AN INSTRUMENT FOR ELICITING AND EVALUATING VOCATIONAL IMAGERY.

    ERIC Educational Resources Information Center

    MATHEWSON, ROBERT H.; ORTON, JOHN W.

    THIS STUDY WAS CONDUCTED TO (1) PRODUCE AN INSTRUMENT FOR ELICITING VOCATIONAL IMAGERY FOR USE IN THE EDUCATIONAL-VOCATIONAL ORIENTATION AND COUNSELING OF HIGH SCHOOL YOUTH, AND (2) DEVELOP A SCALE FOR EVALUATING THE MATURITY OF THE VOCATIONAL IMAGERY ELICITED BY THE INSTRUMENT. A PREVIOUSLY DESIGNED INSTRUMENT "WHAT I THINK OF MYSELF"…

  10. Eliciting Spontaneous Speech in Bilingual Students: Methods & Techniques.

    ERIC Educational Resources Information Center

    Cornejo, Ricardo J.; And Others

    Intended to provide practical information pertaining to methods and techniques for speech elicitation and production, the monograph offers specific methods and techniques to elicit spontaneous speech in bilingual students. Chapter 1, "Traditional Methodologies for Language Production and Recording," presents an overview of studies using…

  11. Elicited Emotions and Cognitive Functioning in Preschool Children

    ERIC Educational Resources Information Center

    Blau, Rivka; Klein, Pnina S.

    2010-01-01

    In this study, the effects of eliciting positive and negative emotions on various cognitive functions of four- to five-year-old preschool children were examined. Emotions were elicited through presentations of "happy" and "sad" video clips, before the children performed the cognitive tasks. Behavioural (facial expressions) and…

  12. Pedagogical use of ELICIT for Leadership Training: Survey and Recommendations

    DTIC Science & Technology

    2011-06-01

    classroom training as part of leadership development programs. ELICIT is particularly helpful in teaching the strengths and weakness of various...organizational structures (edge organization vs. traditional command and control hierarchy.) This paper reviews some of the pedagogical uses of the classroom ...training to date, and provides recommendations for the use of ELICIT in various classroom settings. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF

  13. Freeze or Flee? Negative Stimuli Elicit Selective Responding

    ERIC Educational Resources Information Center

    Estes, Zachary; Verges, Michelle

    2008-01-01

    Humans preferentially attend to negative stimuli. A consequence of this automatic vigilance for negative valence is that negative words elicit slower responses than neutral or positive words on a host of cognitive tasks. Some researchers have speculated that negative stimuli elicit a general suppression of motor activity, akin to the freezing…

  14. Examining of Model Eliciting Activities Developed by Mathematics Student Teachers

    ERIC Educational Resources Information Center

    Dede, Ayse Tekin; Hidiroglu, Çaglar Naci; Güzel, Esra Bukova

    2017-01-01

    The purpose of this study is to examine the model eliciting activities developed by the mathematics student teachers in the context of the principles of the model eliciting activities. The participants of the study conducted as a case study design were twenty one mathematics student teachers working on seven groups. The data collection tools were…

  15. Freeze or Flee? Negative Stimuli Elicit Selective Responding

    ERIC Educational Resources Information Center

    Estes, Zachary; Verges, Michelle

    2008-01-01

    Humans preferentially attend to negative stimuli. A consequence of this automatic vigilance for negative valence is that negative words elicit slower responses than neutral or positive words on a host of cognitive tasks. Some researchers have speculated that negative stimuli elicit a general suppression of motor activity, akin to the freezing…

  16. Science Teachers' Elicitation Practices: Insights for Formative Assessment

    ERIC Educational Resources Information Center

    Ateh, Comfort M.

    2015-01-01

    In evaluating teachers' instructional decisions during instruction, it is clear that the nature of their elicitation is crucial for student learning. When instructional decisions are informed by information about students' conceptual understanding, significant learning is possible. This article examined the elicitation practices of two high school…

  17. Introducing Forum Theatre to Elicit and Advocate Children's Views

    ERIC Educational Resources Information Center

    Hammond, Nick

    2013-01-01

    Eliciting and advocating the voice of the child remains at the heart of international political agenda and also remains a central role for educational psychologists (EPs). Previous research indicates that EPs tend to use language-based methods for eliciting and advocating views of children. However, these approaches are often limited. Taking a…

  18. Prostaglandin E(2) fever mediated by inhibition of the GABAergic transmission in the region immediately adjacent to the organum vasculosum of the lamina terminalis.

    PubMed

    Osaka, Toshimasa

    2008-08-01

    Unilateral microinjection of prostaglandin (PG)E(2) into a region immediately adjacent to the organum vasculosum of the lamina terminalis (peri-OVLT) in the preoptic area elicited thermogenic, tachycardic, cutaneous vasoconstrictive, and hyperthermic responses simultaneously in urethane-chloralose-anesthetized rats. The magnitude of these responses increased dose-dependently over the range of 57 fmol-2.8 pmol, except for the vasoconstrictive response. Microinjection of a GABA(A) receptor antagonist, bicuculline methiodide or gabazine (5-20 pmol), into the PGE(2)-sensitive site in the peri-OVLT region also elicited responses similar to those induced by PGE(2). Although administration of a GABA(A) receptor agonist, muscimol (10 pmol), microinjected into the same site alone usually had no effect on the rate of whole-body O(2) consumption, heart rate or colon and skin temperatures, all PGE(2)-induced responses were blocked 10 min after the muscimol pretreatment and recovered at 50-90 min. Pretreatment with the vehicle, saline, had no effect on the PGE(2)-induced responses. These results suggest that spontaneous release of GABA and tonic activation of GABA(A) receptors in the peri-OVLT region prevent the elevation in the body core temperature under normal circumstances and that PGE(2)-induced febrile responses are mediated, at least in part, by inhibition of the GABAergic transmission in this area.

  19. The effects of E and A prostaglandins on gastric mucosal blood flow and acid secretion in the rat

    PubMed Central

    Main, I. H. M.; Whittle, B. J. R.

    1973-01-01

    1. The effects of prostaglandins E1, E2, A1 and A2 on gastric acid secretion and mucosal blood flow were studied by means of a [14C]-aniline clearance technique in the anaesthetized rat. 2. During intravenous administration of these prostaglandins, in doses which almost completely inhibited pentagastrin- and histamine-induced acid secretion, a fall in clearance was observed. 3. Clearance per unit acid secretion increased during prostaglandin administration, precluding a primary reduction in mucosal blood flow as the mechanism of the antisecretory action. 4. Prostaglandins increased clearance during basal secretion, indicating a direct vasodilator effect on the gastric mucosa. 5. The possibility that endogenous prostaglandins contribute to functional vasodilatation in the gastric mucosa and that exogenous prostaglandins may be of clinical value in the treatment of peptic ulcer is discussed. PMID:4149696

  20. The possible mode of action of prostaglandins: XVI. A study to assess the local effect of prostaglandins E1, E2 or F2 alpha in the regulation of male fertility.

    PubMed

    Rej, S K; Chatterjee, A

    1980-06-01

    A single intratesticular injection of prostaglandin E1 (PGE1) or prostaglandin E2 (PGE2) at a dose of 2.5 mg/kg was found to interfere with the fertilizing ability of epididymal spermatozoa of the test animals both in the injected and contralateral control sides. Prostaglandin F2 alpha, conversely, was found to be ineffective in terms of fertility of the test animals in the same experimental model. The beneficial effect of testosterone therapy concurrently with either of the PGE1 or PGE2 in maintaining the fertility of the animals has been recorded and discussed in terms of the mode of action of prostaglandins.

  1. Prostaglandin concentrations in uterine fluid of cows with pyometra.

    PubMed Central

    Manns, J G; Nkuuhe, J R; Bristol, F

    1985-01-01

    Uterine fluid was obtained from eight clinical cases of pyometra with retained corpus luteum and nine additional samples of fluid were collected from animals slaughtered at an abattoir. These samples, along with uterine flushes from normal cows in their luteal phase were analyzed for prostaglandin of the F (PGF) and E (PGE) groups. Blood samples were also obtained from the clinical cases for analysis of 13,14-dihydro-15-keto PGF (PGFM) the major metabolite of PGF. Pyometrial exudate from clinical cases of abattoir samples had high concentrations of PGF (17.9 ng/mL) and PGE (33.2 ng/mL) and the total amount of PGF and PGE in the uterus was calculated to be several hundred times as great as in normal cows. Furthermore, clinical cases had elevated PGFM in their blood compared to that of controls, which suggests that at least some of the PGF was being absorbed from the uterus. These results are discussed in light of our current understanding of the maternal recognition of pregnancy in cattle. PMID:4075244

  2. Rabbit blastocysts accumulate [3H]prostaglandins in vitro.

    PubMed

    Jones, M A; Harper, M J

    1984-08-01

    Rabbit blastocysts obtained on days 5, 6, and 6.8 of pregnancy were incubated in vitro in Tyrode's buffer with 3H-labeled prostaglandins (PGs). Accumulation of PGs was studied, using Whatman GF/F filters to separate bound and free ligands. The uptake and efflux of [3H]PGs were studied as a function of PG type, incubation time, temperature, and effect of metabolic inhibitors as well as age and number of blastocysts. Blastocysts of the same age accumulated approximately the same amount of [3H]PGE2 and [3H]PGF2 alpha from their environment; however, there was no apparent saturation over a PG concentration range of 1-1000 nM. Both the uptake and efflux of PG were age dependent, with older blastocysts accumulating more PGs. Approximately 90% of the [3H]PGs appear to be transported into the blastocoelic fluid, with little PG remaining in the blastomeres. PG accumulation was relatively insensitive to azide, ouabain, cyanide, or bromcresol green, but was affected by incubation at 0 C or the addition of indomethacin (10 micrograms/ml). No catabolism of the accumulated PGs was observed. The release of PGE2 in general did not differ from that of PGF2 alpha, except on day 6.8 of pregnancy when PGE2 was released more rapidly than on day 6. We conclude that rabbit blastocysts can accumulate PGs from their environment, which may imply a storage potential in the blastocyst and release before implantation.

  3. Prostaglandin FP receptor inhibitor reduces ischemic brain damage and neurotoxicity

    PubMed Central

    Kim, Yun Tai; Moon, Sang Kwan; Maruyama, Takayuki; Narumiya, Shuh; Doré, Sylvain

    2012-01-01

    Bioactive lipids such as the prostaglandins have been reported to have various cytoprotective or toxic properties in acute and chronic neurological conditions. The roles of PGF2α and its receptor (FP) are not clear in the pathogenesis of ischemic brain injury. Considering that this G-protein coupled receptor has been linked to intracellular calcium regulation, we hypothesized that its blockade would be protective. We used FP antagonist (AL-8810) and FP receptor knockout (FP−/−) mice in in vivo and in vitro stroke models. Mice that were treated with AL-8810 had 35.7 ± 6.3% less neurologic dysfunction and 36.4 ± 6.0% smaller infarct volumes than did vehicle-treated mice after 48 hours of permanent middle cerebral artery occlusion (pMCAO); FP−/− mice also had improved outcomes after pMCAO. Blockade of the FP receptor also protected against oxygen-glucose deprivation (OGD)-induced cell death and reactive oxygen species formation in slice cultures. Finally, we found that an FP receptor agonist dose dependently increased intracellular Ca2+ levels in cultured neurons and established that FP-related Ca2+ signaling is related to ryanodine receptor signaling. These results indicate that the FP receptor is involved in cerebral ischemia-induced damage and could promote development of drugs for treatment of stroke and acute neurodegenerative disorders. PMID:22709986

  4. Prostaglandins temporally regulate cytoplasmic actin bundle formation during Drosophila oogenesis.

    PubMed

    Spracklen, Andrew J; Kelpsch, Daniel J; Chen, Xiang; Spracklen, Cassandra N; Tootle, Tina L

    2014-02-01

    Prostaglandins (PGs)--lipid signals produced downstream of cyclooxygenase (COX) enzymes--regulate actin dynamics in cell culture and platelets, but their roles during development are largely unknown. Here we define a new role for Pxt, the Drosophila COX-like enzyme, in regulating the actin cytoskeleton--temporal restriction of actin remodeling during oogenesis. PGs are required for actin filament bundle formation during stage 10B (S10B). In addition, loss of Pxt results in extensive early actin remodeling, including actin filaments and aggregates, within the posterior nurse cells of S9 follicles; wild-type follicles exhibit similar structures at a low frequency. Hu li tai shao (Hts-RC) and Villin (Quail), an actin bundler, localize to all early actin structures, whereas Enabled (Ena), an actin elongation factor, preferentially localizes to those in pxt mutants. Reduced Ena levels strongly suppress early actin remodeling in pxt mutants. Furthermore, loss of Pxt results in reduced Ena localization to the sites of bundle formation during S10B. Together these data lead to a model in which PGs temporally regulate actin remodeling during Drosophila oogenesis by controlling Ena localization/activity, such that in S9, PG signaling inhibits, whereas at S10B, it promotes Ena-dependent actin remodeling.

  5. Sequential induction of prostaglandin E and D synthases in inflammation

    SciTech Connect

    Schuligoi, Rufina . E-mail: rufina.schuligoi@meduni-graz.at; Grill, Magdalena; Heinemann, Akos; Peskar, Bernhard A.; Amann, Rainer

    2005-09-30

    Enhanced biosynthesis of prostaglandin (PG)D{sub 2} and subsequent formation of 15-deoxy-{delta}{sup 12,14}-PGJ{sub 2} has been suggested to contribute to resolution of inflammation. The primary aim of the present study in mouse heart was, therefore, to determine at the transcriptional level if there is sequential induction of PGE and PGD synthases (S) during inflammation. Expression of interleukin (IL)-1{beta} in heart was enhanced 4 h after systemic inflammation and declined thereafter within 3-5 days to basal levels. In contrast to cyclooxygenase-2 and membrane-bound (m)-PGES-1, which both peaked 4 h after endotoxin administration, hematopoietic (H)-PGDS expression was enhanced only 48 h after endotoxin. The expression of lipocalin-type (L)-PGDS was not significantly influenced. mRNA encoding the putative target of 15-deoxy-{delta}{sup 12,14}-PGJ{sub 2}, peroxisome proliferator-activated receptor {gamma}, was enhanced between 4 and 24 h after induction of inflammation. Treatment of mice with acetylsalicylic acid or indomethacin at doses effective to cause near-complete inhibition of PGE{sub 2} and PGD{sub 2} biosynthesis in heart ex vivo resulted in enhanced expression of IL-1{beta} 24 h after endotoxin administration. These results provide additional support for the hypothesis of a shift towards PGD{sub 2} biosynthesis during resolution of inflammation.

  6. Discovery of anti-inflammatory role of prostaglandin D2

    PubMed Central

    MURATA, Takahisa; MAEHARA, Toko

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin are one of the most frequently used classes of drug worldwide and inhibit prostaglandin (PG) production by inhibiting cyclooxygenase activity. Although NSAIDs are broadly used against inflammatory diseases, they have side effects including alimentary canal disorders, kidney damage, infection and cardiovascular disorders. Thus, it is necessary to elucidate the pathophysiological role of each PG in various diseases to develop better therapies with fewer and milder side effects. PGD2 is a PG that was identified in 1973 by Hamberg and is produced by the activities of cyclooxygenase and either hematopoietic or lipocalin-type PGD synthase. PGD2 exerts its physiological effects by stimulating two distinct G protein-coupled receptors, namely D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). The physiological role of PGD2 remains controversial. Some studies have reported that PGD2 has bronchoconstrictory and pro-inflammatory effects inducing immune cell accumulation. In contrast, other groups have reported that PGD2 has anti-inflammatory effects by inhibiting the recruitment of dendritic cells and neutrophils. We have investigated the pathophysiological role of PGD2 using various disease models and reported on its anti-inflammatory actions. Here, we review the anti-inflammatory roles of PGD2 and the underlying mechanisms. PMID:27498997

  7. Prostaglandin E2 Prevents Disuse-Induced Cortical Bone Loss

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Akamine, T.; Ke, Hua Zhu; Li, Xiao Jian; Tang, L. Y.; Zeng, Q. Q.

    1992-01-01

    The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent disuse (underloaded)-induced cortical bone loss as well as add extra bone to underloaded bones. Thirteen-month-old retired female Sprague-Dawley breeders served as controls or were subjected to simultaneous right hindlimb immobilization by bandaging and daily subcutaneous doses of 0, 1, 3, or 6 mg PGE2/kg/d for two and six weeks. Histomorphometric analyses were performed on double-fluorescent labeled undecalcified tibial shaft sections (proximal to the tibiofibular junction). Disuse-induced cortical bone loss occurred by enlarging the marrow cavity and increasing intracortical porosity. PGE2 treatment of disuse shafts further increased intracortical porosity above that in disuse alone controls. This bone loss was counteracted by enhancement of periosteal and corticoendosteal bone formation. Stimulation of periosteal and corticoendosteal bone formation slightly enlarged the total tissue (cross-sectional) area and inhibited marrow cavity enlargement. These PGE2-induced activities netted the same percentage of cortical bone with a different distribution than the beginning and age related controls. These findings indicate the PGE2-induced increase in bone formation compensated for the disuse and PGE2-induced bone loss, and thus prevented immobilization induced bone loss.

  8. [Prostaglandin E₂: innovative approaches for tissue engineering of articular cartilage].

    PubMed

    Brochhausen-Delius, C

    2014-11-01

    Chronic diseases, traumatic tissue defects and tumor resections lead to irreversible loss of tissue which are usually treated by reconstructive techniques or prostheses. Tissue engineering represents a change of paradigm from the structural replacement of damaged tissue to genuine regeneration of organ-specific tissue with reconstruction of function. Therefore, autologous cells, biomaterials and growth factors are used to achieve this goal. Tissue engineering of articular cartilage is used in this article as an example of the successful identification of prostaglandin E2 (PGE2) as a growth factor during endochondral ossification. In addition PGE2 could be shown to be beneficial for a rapid phenotypical redifferentiation and synthesis of collagen II in human articular chondrocytes. Based on these findings the development of a combined construct of an oriented scaffold and release system is demonstrated. The innovative characterization of these cell-seeded constructs by the use of synchrotron microcomputed tomography (μCT) permits non-destructive analysis even down to the cellular level. Our results indicate new requirements for the pathological anatomical diagnosis with a view to long-term effects of tissue engineering constructs, the biocompatibility of biodegradable biomaterials and even more important the regenerative potential of different lesions, with prediction of the outcome of tissue engineering-based strategies for individual patients.

  9. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.

    PubMed

    Cutler, Corey; Multani, Pratik; Robbins, David; Kim, Haesook T; Le, Thuy; Hoggatt, Jonathan; Pelus, Louis M; Desponts, Caroline; Chen, Yi-Bin; Rezner, Betsy; Armand, Philippe; Koreth, John; Glotzbecker, Brett; Ho, Vincent T; Alyea, Edwin; Isom, Marlisa; Kao, Grace; Armant, Myriam; Silberstein, Leslie; Hu, Peirong; Soiffer, Robert J; Scadden, David T; Ritz, Jerome; Goessling, Wolfram; North, Trista E; Mendlein, John; Ballen, Karen; Zon, Leonard I; Antin, Joseph H; Shoemaker, Daniel D

    2013-10-24

    Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates, and early mortality. 16,16-Dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis, and we hypothesized that brief ex vivo modulation with dmPGE2 could improve patient outcomes by increasing the "effective dose" of HSCs. Molecular profiling approaches were used to determine the optimal ex vivo modulation conditions (temperature, time, concentration, and media) for use in the clinical setting. A phase 1 trial was performed to evaluate the safety and therapeutic potential of ex vivo modulation of a single UCB unit using dmPGE2 before reduced-intensity, double UCB transplantation. Results from this study demonstrated clear safety with durable, multilineage engraftment of dmPGE2-treated UCB units. We observed encouraging trends in efficacy, with accelerated neutrophil recovery (17.5 vs 21 days, P = .045), coupled with preferential, long-term engraftment of the dmPGE2-treated UCB unit in 10 of 12 treated participants.

  10. Possible role of prostaglandin F in blastocyst implantation

    SciTech Connect

    Kasamo, M.; Ishikawa, M.; Yamashita, K.; Sengoku, K.; Shimizu, T.

    1986-02-01

    The synthesis and release of Prostaglandin F (PGF) by the rabbit blastocyst and endometrium were investigated on Day 6 and Day 7, using radioimmunoassay, autoradiography and conversion experiments. The following results were obtained: The content of PGF in the blastocyst increased significantly (P less than 0.01) from Day 6 to Day 7. The content of PGF in the endometrium was significantly higher (P less than 0.05) on Day 7 implantation sites compared to the other areas. The in vitro synthesis and release of PGF by Day 6 blastocysts sharply increased after one and two hours of culture, respectively. Thereafter both values declined with time. The in vitro synthesis and release of PGF by Day 6 endometria increased continuously with time. /sup 14/C-arachidonic acid (/sup 14/C-AA) was incorporated into Day 6 blastocysts in vitro and converted to PGF2 alpha. These results suggest that both the endometrium and the blastocyst are the sources of the PGs involved in implantation, and that PGF derived from the blastocysts may act as the trigger of implantation.

  11. Prostaglandin F in patients with primary affective disorder.

    PubMed

    Gross, H A; Dunner, D L; Lafleur, D; Meltzer, H L; Fieve, R R

    1977-06-01

    Two aspects of prostaglandin F (PGF) metabolism were assessed in patients with primary affective disorder. For a group of hospitalized patients cerebrospinal fluid PGF was measured by radioimmunoassay and the effects of probenecid and L-tryptophan were determined. For outpatients attending our Lithium Clinic, plasma PGF was measured and the acute and chronic effects of lithium were determined. The results of the studies reveal apparently normal concentrations of PGF in cerebrospinal fluid. These concentrations increase twofold after probenecid, indicating that PGF is transported out of the central nervous system by a probenecid-sensitive active transport system. Evidence for inhibition of PGF synthesis during L-tryptophan treatment was found. The results for outpatient plasma studies suggest no effect on PGF with 12 weeks of lithium treatment, although a slight elevation of plasma PGF with chronic lithium treatment may occur. Specificity of the assay technique as applied to plasma is discussed. This is the first report of the direct measurement of PGF in a psychiatric disorder.

  12. Prostaglandin signaling suppresses beneficial microglial function in Alzheimer's disease models.

    PubMed

    Johansson, Jenny U; Woodling, Nathaniel S; Wang, Qian; Panchal, Maharshi; Liang, Xibin; Trueba-Saiz, Angel; Brown, Holden D; Mhatre, Siddhita D; Loui, Taylor; Andreasson, Katrin I

    2015-01-01

    Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer's disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE2) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aβ peptides and determined that microglia-specific deletion of the gene encoding the PGE2 receptor EP2 restores microglial chemotaxis and Aβ clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE2/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD.

  13. Prostaglandins and adenosine in the regulation of sleep and wakefulness.

    PubMed

    Huang, Zhi-Li; Urade, Yoshihiro; Hayaishi, Osamu

    2007-02-01

    Prostaglandin (PG) D2 and adenosine are potent humoral sleep-inducing factors that accumulate in the brain during prolonged wakefulness. PGD2 is produced in the brain by lipocalin-type PGD synthase, which is localized mainly in the leptomeninges, choroid plexus and oligodendrocytes, and circulates in the cerebrospinal fluid as a sleep hormone. It stimulates DP1 receptors on leptomeningeal cells of the basal forebrain to release adenosine as a paracrine signaling molecule to promote sleep. Adenosine activates adenosine A2A receptor-expressing sleep-active neurons in the basal forebrain and the ventrolateral preoptic area. Sleep-promoting neurons in the ventrolateral preoptic area send inhibitory signals to suppress the histaminergic neurons in the tuberomammillary nucleus, which contribute to arousal through histamine H1 receptors. Increased knowledge of the molecular mechanisms by which PGD2 induces sleep through activation of adenosine A2A receptors and inhibition of the histaminergic arousal system will be useful both for a better understanding of sleep/wake regulation and for the development of novel types of sleeping pills or anti-doze drugs.

  14. Prostaglandin E2 As a Modulator of Viral Infections

    PubMed Central

    Sander, Willem J.; O'Neill, Hester G.; Pohl, Carolina H.

    2017-01-01

    Viral infections are a major cause of infectious diseases worldwide. Inflammation and the immune system are the major host defenses against these viral infection. Prostaglandin E2 (PGE2), an eicosanoid generated by cyclooxygenases, has been shown to modulate inflammation and the immune system by regulating the expression/concentration of cytokines. The effect of PGE2 on viral infection and replication is cell type- and virus-family-dependent. The host immune system can be modulated by PGE2, with regards to immunosuppression, inhibition of nitrogen oxide (NO) production, inhibition of interferon (IFN) and apoptotic pathways, and inhibition of viral receptor expression. Furthermore, PGE2 can play a role in viral infection directly by increasing the production and release of virions, inhibiting viral binding and replication, and/or stimulating viral gene expression. PGE2 may also have a regulatory role in the induction of autoimmunity and in signaling via Toll-like receptors. In this review the known effects of PGE2 on the pathogenesis of various infections caused by herpes simplex virus, rotavirus, influenza A virus and human immunodeficiency virus as well the therapeutic potential of PGE2 are discussed. PMID:28261111

  15. Letter: intrauterine prostaglandins for outpatient termination of very early pregnancy.

    PubMed

    Karim, S M

    1973-10-06

    The efficacy of PGs (prostaglandins) in terminating human pregnancy has been repeatedly demonstrated. The disadvantages associated with systemic administration of PGs can be overcome by use of other routes of administration. Single intraamniotic injections of PGE2 or PGF2alpha will cause 2nd-trimester terminations in most cases. PGs used for 1st-trimester procedures have proven unsuccessful due to the high rate of incomplete abortions produced. An ideal fertility control method would be self-administration of PGs during very early pregnancy. Vaginal administration of PGs has produced high rates of side effects and extrauterine PG administration has required repeated dosing, too much time, and hospital admission. Recent experimentation was carried out using PGE2 or PGF2alpha administered via the cervix into the uterine cavity. A single dose of 1 mg PGE2 or 4 mg PGF2alpha gave the most consistent results, onset of bleeding within 2-5 hours and a negative pregnancy test within 14 days. Higher doses of either substance caused severe gastric side effects. Clinical trials with larger groups are needed to confirm the study findings.

  16. Prostaglandin E2 Mediates Immunosuppression in Acutely Decompensated Cirrhosis

    PubMed Central

    O’Brien, Alastair J.; Fullerton, James N.; Massey, Karen A.; Auld, Grace; Sewell, Gavin; James, Sarah; Newson, Justine; Karra, Effie; Winstanley, Alison; Alazawi, William; Garcia-Marquez, Rita; Cordoba, Juan; Nicolaou, Anna; Gilroy, Derek W.

    2017-01-01

    Patients with advanced cirrhosis experience frequent infections leading to sepsis, which carries high mortality. While innate immune dysfunction underlies this vulnerability, the precise cause remains elusive. We found prostaglandin (PGE2) elevated in acutely decompensated (AD) patients at immunosuppressive levels. Plasma from AD and end-stage liver disease (ESLD) patients suppressed macrophage cytokine secretion and bacteria killing in a PGE2 receptor-dependent manner, effects not seen in stable cirrhosis. Mouse models (bile duct ligation and CCL4-liver injury) also demonstrated elevated PGE2, which when inhibited completely restored immune competence and survival following infection. Importantly, albumin binds/inactivates PGE2 resulting in greater PGE2 bioavailability. This results in enhanced immunosuppressive effects of AD plasma in patients with low albumin levels. Administering albumin to AD patients reversed immunosuppressive properties of their plasma; protective effects recapitulated in rodent survival studies. Thus, elevated PGE2 combined with hypoalbuminemia mediates immunosuppression in AD and ESLD patients, which can be reversed with albumin. PMID:24728410

  17. [Morphologic and biochemical aspects of prostaglandin-induced cervix ripening].

    PubMed

    Rath, W; Adelmann-Grill, B C; Schauer, A; Kuhn, W

    1987-01-01

    For examination by electron microscopy tissue samples were taken from the posterior lip of the cervix of 8 patients having a termination of pregnancy at 9-12th week gestation and 16 patients of comparable gestational age who had an intracervical application of either 2 ml 5% tylose or 50 micrograms sulprostone-tylose gel 8 hours before biopsy. The efficacy of cervical priming was demonstrated objectively by tonometric studies. In addition, collagenase and protease activities were determined in the cervical tissue extracts of the different treatment groups. For identification of typical collagen fragments SDS-polyacrylamide-gel-electrophoresis were carried out on the acetic acid soluble extracts. The local application of sulprostone gel induced a marked multifocal loosening of the collagenous framework; there was no evidence for leucocyte infiltration or necrosis caused by the prostaglandin (PG) pretreatment. In the areas of disorganized collagen fibres cervical fibroblasts seemed to be activated characterized by fine granular loosening of the cytoplasma, dilated cisternae of rough endoplasmatic reticulum, vacuolized enlarged mitochondria and an increased number of cytoplasmatic vesicles close to the cell surface. Collagenase and protease activities were found in all extracts of the different treatment groups, however, PG-application led to no significant increase in enzymatic activities. There was no evidence for the presence of typical collagen cleavage products in the SDS-electrophoresis. Contradictory to the hitherto published literature enzymatic collagen degradation does not play an essential role in PG-induced cervical ripening.

  18. Anti-inflammatory prostaglandins for the prevention of preterm labour.

    PubMed

    Sykes, Lynne; MacIntyre, David A; Teoh, Tiong Ghee; Bennett, Phillip R

    2014-08-01

    Preterm birth occurs in 10-12% of pregnancies and is the primary cause of neonatal mortality and morbidity. Tocolytic therapies have long been the focus for the prevention of preterm labour, yet they do not significantly improve neonatal outcome. A direct causal link exists between infection-induced inflammation and preterm labour. As inflammation and infection are independent risk factors for poor neonatal outcome, recent research focus has been shifted towards exploring the potential for anti-inflammatory strategies. Nuclear factor kappa B (NFκB) is a transcription factor that controls the expression of many labour-associated genes including PTGS2 (COX2), prostaglandins (PGs) and the oxytocin receptor (OXTR) as well as key inflammatory genes. Targeting the inhibition of NFκB is therefore an attractive therapeutic approach for both the prevention of preterm labour and for reducing neonatal exposure to inflammation. While PGs are considered to be pro-labour and pro-inflammatory, the cyclopentenone PG 15-deoxy-Δ(12,14)PGJ2 (15d-PGJ2) exhibits anti-inflammatory properties via the inhibition of NFκB in human amniocytes, myocytes and peripheral blood mononuclear cells in vitro. 15d-PGJ2 also delays inflammation-induced preterm labour in the mouse and significantly increases pup survival. This review examines the current understanding of inflammation in the context of labour and discusses how anti-inflammatory PGs may hold promise for the prevention of preterm labour and improved neonatal outcome.

  19. Adverse periocular reactions to five types of prostaglandin analogs

    PubMed Central

    Inoue, K; Shiokawa, M; Higa, R; Sugahara, M; Soga, T; Wakakura, M; Tomita, G

    2012-01-01

    Purpose We investigated the appearance frequency of eyelid pigmentation and eyelash bristles after the use of five types of prostaglandin (PG) analogs. Methods This study included 250 eyes from 250 patients diagnosed with primary open-angle glaucoma or ocular hypertension who were treated with either latanoprost, travoprost, tafluprost, bimatoprost, or isopropyl unoprostone for >3 months in only one eye. Photographs of both eyes were obtained, and the images were assessed by three ophthalmologists who were masked to treatment type. The existence of eyelid pigmentation and eyelash bristles was judged, and images of the left and right eyes were compared. Subjective symptoms regarding the existence of eyelid pigmentation and eyelash bristles were investigated through a questionnaire. Results There was no significant difference between the five types of medications with regard to eyelid pigmentation (P=0.537). Use of isopropyl unoprostone resulted in a significantly lower incidence of eyelash bristles (P<0.0001). The questionnaire investigation showed that eyelid pigmentation and eyelash bristles were significantly more frequent with travoprost (42.0% and 42.0%, respectively) and bimatoprost (58.0% and 60.0%, respectively) than with other three medications (P<0.0001). Conclusion The appearance frequency of eyelid pigmentation was similar among the five types of PG analogs studied, and eyelash bristles appeared less frequently with isopropyl unoprostone use. Patients are conscious of eyelash bristles; therefore, these adverse effects should be sufficiently explained to patients before PG administration. PMID:23037910

  20. Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting

    PubMed Central

    Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Alshahrani, Saeed; Brooks, Marybeth; McCormack, Francis X.; Smith, Roger D.; Zahedi, Kamyar

    2016-01-01

    Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO) mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2) and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE) levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2) in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR) reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of sodium and

  1. Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting.

    PubMed

    Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Alshahrani, Saeed; Brooks, Marybeth; McCormack, Francis X; Smith, Roger D; Zahedi, Kamyar

    2016-01-01

    Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO) mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2) and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE) levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2) in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR) reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of sodium and

  2. Stage-dependent reduction in T colony formation in Hodgkin's disease. Coincidence with monocyte synthesis of prostaglandins.

    PubMed Central

    Bockman, R S

    1980-01-01

    Prostaglandin synthesis and T lymphocyte colony formation have been examined in previously untreated patients with Hodgkin's disease. Mononuclear cells have been isolated from peripheral blood and spleens of these patients. Significant augmentation in prostaglandin E levels were noted in the mononuclear cell cutures from Hodgkin's disease patients compared with controls (1.64 +/- 0.29 vs. 0.39 +/- 0.09 ng/10(6) cells, P < 0.005). Measured prostaglandin E levels increased with advancing stage of disease. Virtually all of the prostaglandins were synthesized by the adherent monocyte cell population. Prostaglandin E was the major product. Clonal expansion of a T lymphocyte precursor cell, which gives rise to colonies > 50 cells, was determined by a layered soft agar method. T colony formation was significantly reduced in patients with stage II, III, and IV disease. There were progressively reduced colony numbers seen with advancing stage of disease (609 +/- 209, 416 +/- 158, 207 +/- 58 compared with normals 2,274 +/- 360 colonies/10(6) cells plated; P < 0.005). The addition of inhibitors of endogenous prostaglandin synthesis resulted in significant augmentation of T colony number. However, a consistent relative decrease in T colony number was seen even when endogenous prostaglandin E synthesis was blocked. It would appear that both the prostaglandin-dependent and independent T colony precursor cells are lost with progressive stage of disease. A causative role of augmented prostaglandin synthesis in this stage-dependent reduction of T colony formation could not be established. PMID:6967491

  3. Effects of indomethacin on plasma homovanillic acid concentration in normal subjects: a study of prostaglandin-dopamine interactions.

    PubMed

    Kahn, R S; Davidson, M; Kanof, P; McQueeney, R T; Singh, R R; Davis, K L

    1991-01-01

    In laboratory animals, prostaglandins have been shown to act as endogenous neuromodulators of central dopamine (DA) activity. To examine the interaction between prostaglandins and DA in man, the effect of a prostaglandin synthesis inhibitor, indomethacin, was studied on plasma concentrations of the DA metabolite, homovanillic acid (pHVA). Indomethacin (150 mg PO) as compared to placebo significantly elevated mean pHVA concentrations in eight normal subjects. Results of this study support the hypothesis that, as in animals, inhibition of prostaglandin synthesis increases central DA turnover in man.

  4. Histamine and prostaglandin interaction in regulation of oxytocin and vasopressin secretion.

    PubMed

    Knigge, U; Kjaer, A; Kristoffersen, U; Madsen, K; Toftegaard, C; Jørgensen, H; Warberg, J

    2003-10-01

    Prostaglandins and histamine in the hypothalamus are involved in the regulation of oxytocin and vasopressin secretion, and appear to be involved in the mediation of pituitary hormone responses to immunochallenges. Therefore, we investigated in conscious male rats: (i) whether blockade of H1 or H2 receptors affected the oxytocin and vasopressin responses to prostaglandins and (ii) whether blockade of prostaglandin synthesis affected the oxytocin and vasopressin responses to histamine or to Escherichia coli lipopolysaccharide (LPS), in order to determine any interaction between prostaglandins and histamine in the hypothalamus. Oxytocin secretion was dose-dependently stimulated by intracerebroventricular infusion of 1 or 5 microg of PGE1, PGE2 or PGF2alpha, with PGE2 being the most potent of the compounds used. Prior central infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine significantly inhibited the oxytocin response to all three prostaglandins by approximately 50%. Vasopressin secretion was increased by PGE1 but not by PGE2 or PGF2alpha. The stimulatory effect of PGE1 was almost annihilated by prior administration of mepyramine or cimetidine. Central infusion of histamine or immunochallenge with LPS administered intraperitoneally increased oxytocin and vasopressin secretion four- and two-fold, respectively. Pretreatment with systemic injection of the prostaglandin synthesis inhibitor indomethacin dose-dependently reduced the oxytocin response and prevented the vasopressin response to histamine or LPS. We conclude that histamine and PGE1, PGE2 or PGF2alpha interact in the regulation of oxytocin secretion, whereas histamine and only PGE1 interact in the regulation of vasopressin secretion. Furthermore, histamine as well as LPS may affect oxytocin and vasopressin neurones via activation of prostaglandins, probably in the hypothalamic supraoptic nucleus.

  5. Prostaglandin E production and hypercalcaemia in rats bearing the Walker carcinosarcoma.

    PubMed

    Seyberth, H W; Bonsch, G; Müller, H; Minne, H W; Erlenmaier, T; Strein, K; Imbeck, H; Mrongovius, R

    1980-09-01

    The hypothesis that there is prostaglandin-mediated hypercalcaemia associated with the Walker carcinosarcoma in the rat was tested by measuring PGE production during the development of the hypercalcaemia, and determining the effects of inhibition of prostaglandin synthesis on serum calcium concentration. Parathyroid hormone (PTH) activity was estimated by the determination of the serum concentration of immunoreactive PTH. There was a 3-fold increase in the urinary excretion of 7α-hydroxy-5,11-diketotetranor-prostane-1,16-dioic acid (PGE-M), a major urinary metabolite of the E prostaglandins from basal levels. Treatment with indomethacin, a potent inhibitor of prostaglandin synthesis, did not lower serum calcium concentrations with two different doses (1·6 mg/kg/day orally and 5 mg/kg/day i.m.); effective inhibition of prostaglandin synthesis was demonstrated by the suppression of PGE-M excretion rates below basal levels. Serum concentrations of immunoreactive PTH were not significantly altered by either tumour growth or indomethacin. Dexamethasone (0·5 mg/kg/day i.m.) attenuated both the increased urinary excretion of PGE-M and the rise in serum calcium concentration, suggesting that one or several lipoxygenase products might be the actual mediators of the hypercalcaemia. We conclude that the hypercalcaemia in the rat with Walker carcinosarcoma is probably not mediated by E-prostaglandins and probably not by any other product of the cyclo-oxygenase pathway. The increased PGE turnover may be considered as a biochemical marker of tumour load, but not as an indicator of a prostaglandin-mediated hypercalcaemia.

  6. Prostaglandin E production and hypercalcaemia in rats bearing the Walker carcinosarcoma

    PubMed Central

    Seyberth, H. W.; Bonsch, G.; Müller, H.; Minne, H. W.; Erlenmaier, T.; Strein, K.; Imbeck, H.; Mrongovius, R.

    1980-01-01

    The hypothesis that there is prostaglandin-mediated hypercalcaemia associated with the Walker carcinosarcoma in the rat was tested by measuring PGE production during the development of the hypercalcaemia, and determining the effects of inhibition of prostaglandin synthesis on serum calcium concentration. Parathyroid hormone (PTH) activity was estimated by the determination of the serum concentration of immunoreactive PTH. There was a 3-fold increase in the urinary excretion of 7α-hydroxy-5,11-diketotetranor-prostane-1,16-dioic acid (PGE-M), a major urinary metabolite of the E prostaglandins from basal levels. Treatment with indomethacin, a potent inhibitor of prostaglandin synthesis, did not lower serum calcium concentrations with two different doses (1·6 mg/kg/day orally and 5 mg/kg/day i.m.); effective inhibition of prostaglandin synthesis was demonstrated by the suppression of PGE-M excretion rates below basal levels. Serum concentrations of immunoreactive PTH were not significantly altered by either tumour growth or indomethacin. Dexamethasone (0·5 mg/kg/day i.m.) attenuated both the increased urinary excretion of PGE-M and the rise in serum calcium concentration, suggesting that one or several lipoxygenase products might be the actual mediators of the hypercalcaemia. We conclude that the hypercalcaemia in the rat with Walker carcinosarcoma is probably not mediated by E-prostaglandins and probably not by any other product of the cyclo-oxygenase pathway. The increased PGE turnover may be considered as a biochemical marker of tumour load, but not as an indicator of a prostaglandin-mediated hypercalcaemia. PMID:7426347

  7. [Plasma hormone concentrations in induced abortion with local prostaglandin administration in the 1st trimester].

    PubMed

    Rath, W; König, A; Ulbrich, R; Hilgers, R; Kuske, R; Kuhn, W

    1983-01-01

    Abortion was performed by curettage on 71 women with pregnancies between the 7th and the 13th week of gestation seven to eight hours after intracervical application of a tylose gel containing 3mg prostaglandin F2 alpha. Prior to the application of the prostaglandin and immediately before the surgical intervention a sonographic examination for determining the vitality of the pregnancy was carried out.--Plasma progesteron, estradiol and HPL levels were determined radioimmunologically prior to the application of prostaglandin, at four-hour intervals on the day of intervention, and 24, 48 and 72 hours after the intervention. In 22 women a complete or an incomplete abortion occurred; in two cases a blighted ovum was observed; 47 pregnancies, according to sonographic examination, remained intact until curettage. After seven to eight hours duration of the effect of the prostaglandin gel, progesterone levels were found to be reduced to 60.5 per cent and 17-beta-estradiol to 31.4 per cent of the initial values, whereas the HPL values fell below the specificity of the testing procedure (12.5 ng/ml). Comparative investigations of the pregnancies which, according to sonographic findings, remained intact until curettage and those which were aborted after the application of prostaglandin did not, in spite of low plasma progesterone and estradiol levels in the abortive group, reveal any statistically significant differences. The abortive effect--even with local application--of the prostaglandins was confirmed. Conclusions regarding the effective mechanism of the prostaglandins upon the fetoplacental unit and the function of the corpus luteum remain subject to speculation.

  8. Piglet mortality: the impact of induction of farrowing using prostaglandins and oxytocin.

    PubMed

    Kirkden, R D; Broom, D M; Andersen, I L

    2013-04-01

    Induction is usually carried out by administering prostaglandins (prostaglandin F2α or a synthetic analogue). Other hormones, most commonly oxytocin, may also be given. The primary objective is to increase the synchrony of farrowing. This facilitates farrowing supervision, early fostering and 'all in, all out' management of the farrowing house, all of which have the potential to decrease piglet mortality. However, there are also risks, including decreased piglet viability when farrowing is induced too early and an increased probability of dystocia associated with oxytocin use. What are the effects of induction procedures on mortality in pigs? With respect to prostaglandins, studies show that the date of induction and the level of supervision provided are important factors affecting piglet mortality. We recommend administering prostaglandins no earlier than 2d before the expected farrowing date for the herd. Some studies have reported that prostaglandin induction decreases stillbirth and live-born mortality and this is probably due to increased farrowing supervision. The incidence of postpartum dysgalactia syndrome is also decreased in herds with a high prevalence of this condition. Inconsistent effects on the progress of farrowing are reported following the routine administration of oxytocin 20-24h after prostaglandin. Although there is generally no effect on stillbirth rate, dystocia may increase. Earlier administration of low doses may decrease stillbirths, but this requires further research. Carbetocin, a long-acting analogue of oxytocin, is a possible alternative. We recommend that prostaglandin induction be used in conjunction with skilled farrowing supervision to decrease piglet mortality. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Prostaglandin F{sub 2{alpha}} regulates cytokine responses of mast cells through the receptors for prostaglandin E

    SciTech Connect

    Kaneko, Izumi; Hishinuma, Takanori; Suzuki, Kaori; Owada, Yuji; Kitanaka, Noriko; Kondo, Hisatake; Goto, Junichi; Furukawa, Hiroshi; Ono, Masao

    2008-03-14

    There is an increasing body of evidence that prostanoids modulate mast cell functions and contribute to the development of allergic inflammation. The present study aimed to identify an undetermined function of prostaglandin (PG) F{sub 2{alpha}} in mast cell activation and the signaling mechanism involved in it. Simultaneous quantification of prostanoids by liquid chromatography/tandem mass spectrometry revealed the constitutive release of PGF{sub 2{alpha}}, thromboxane B{sub 2}, and 6-keto-PGF{sub 1{alpha}} from bone marrow-derived mast cells (BMMCs). Upon activation of BMMCs by lipopolysaccharide, the cytokine production in BMMCs was enhanced when the culture was supplemented with PGF{sub 2{alpha}}. However, F prostanoid receptor-a selective receptor for PGF{sub 2{alpha}}-was not detected in BMMCs. Further investigations performed using prostanoid receptor antagonists revealed an alternative mechanism wherein the receptors for PGE species-E prostanoid receptors-mediated the PGF{sub 2{alpha}} signal in BMMCs. The present study provides an insight into a novel function of PGF{sub 2{alpha}}, i.e., an autocrine accelerator for mast cell activation.

  10. Long-term anabolic effects of prostaglandin-E2 on tibial diaphyseal bone in male rats

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Ke, Hua Zhu; Li, Xiao Jian

    1991-01-01

    The effects of long-term prostaglandin E2 (PGE2) on tibial diaphyseal bone were studied in 7-month-old male Sprague-Dawley rats given daily subcutaneous injections of 0, 1, 3 and 6 mg PGE2/kg/day for 60, 120 and 180 days. The tibial shaft was measured by single photon absorptiometry and dynamic histomorphometric analyses were performed on double-fluorescent labeled undecalcified tibial diaphyseal bone samples. Exogenous PGE2 administration produced the following transient changes in a dose-response manner between zero and 60 days: (1) increased bone width and mineral density; (2) increased total tissue and total bone areas; (3) decreased marrow area; (4) increased periosteal and corticoendosteal lamellar bone formation; (5) activated corticoendosteal lamellar and woven trabecular bone formation; and (6) activated intracortical bone remodeling. A new steady-state of increased tibial diaphyseal bone mass and elevated bone activities were observed from day 60 onward. The elevated bone mass level attained after 60 days of PGE2 treatment was maintained at 120 and 180 days. These observations indicate that the powerful anabolic effects of PGE2 will increase both periosteal and corticoendosteal bone mass and sustain the transient increase in bone mass with continuous daily administration of PGE2.

  11. Circadian and estral changes in the hypothalamic prostaglandin e content and [h]prostaglandin e binding in female rats.

    PubMed

    Bommelaer-Bayet, M C; Wisner, A; Renard, C A; Levi, F A; Dray, F

    1990-04-01

    Abstract Prostaglandin E(2), (PGE(2)) is involved in the luteinizing hormone-releasing hormone-stimulated luteinizing hormone surge in female rats and may act via specific membrane receptors. The following studies were performed to determine whether there were any changes in the hypothalamic PGE(2) binding and/or PGE(2) content which were specific to proestrus and not to the rest of the estrous cycle. Groups of female Wistar rats were sacrificed at 3-h intervals throughout the estrous cycle to determine both the circadian and circaestral changes in the hypothalamic PGE(2) content and [(3)H]PGE(2) binding. The hypothalamic PGE(2) content was maximal at 1700 h on each of the 4 consecutive days of the estrous cycle but was independent of the stage of the cycle. [(3)H]PGE(2) binding also displayed a circadian rhythm; the lowest binding occurred near the circadian peak of PGE(2), suggesting that the PGE(2) binding sites were occupied by endogenous PGE(2). Since such circadian rhythms were not observed in the hypothalamus of male rats, they may be under the control of ovarian steroids. Also, since PGE(2) binding and the PGE(2) content both exhibit a diurnal pattern independent of the day of the cycle, there may be changes in the PGE(2) receptor-mediated process coupled to an adenylyl cyclase which could explain the luteinizing hormone surge in proestrus.

  12. Prostaglandin protection of human isolated gastric glands against indomethacin and ethanol injury. Evidence for direct cellular action of prostaglandin.

    PubMed Central

    Tarnawski, A; Brzozowski, T; Sarfeh, I J; Krause, W J; Ulich, T R; Gergely, H; Hollander, D

    1988-01-01

    Isolated human gastric glands from surgical specimens were preincubated in an oxygenated medium with placebo or 16,16 dimethyl prostaglandin E2 (dmPGE2) and incubated at 37 degrees C in either medium alone, medium containing 4.43 mM indomethacin or medium containing 8% ethanol. We assessed the viability of gland cells with fast green exclusion, release of lactate dehydrogenase (LDH) into the medium, and ultrastructural damage by scanning and transmission electron microscopy. Both indomethacin and ethanol significantly reduced the viability of placebo-pretreated glands, increased LDH release into the medium, and produced prominent ultrastructural damage. DmPGE2 significantly reduced both indomethacin and ethanol-induced injury, increased the number of viable cells, reduced LDH release, and diminished the extent of ultrastructural damage. These studies indicate that PG protection of gastric mucosal cells has a direct cellular action that is not limited to replacement of depleted endogenous PGs. PG protection in our experiments did not depend on PG's previously described systemic actions, such as protection of the microvessels, preservation of the mucosal blood flow, or stimulation of bicarbonate and mucus secretion. Images PMID:3350966

  13. Prostaglandin F2alpha added to extended boar semen at processing elicits in vitro myometrial contractility after 72 hours of storage.

    PubMed

    Cheng, H; Althouse, G C; Hsu, W H

    2001-06-01

    Improved fertility will maximize productivity of the swine industry. Myometrial contractility is an essential component in the fertilization process because it is the mechanism by which spermatozoa are transported to the site of fertilization. In the present study, we evaluated the potential use of PGF2alpha supplementation to the extended pig semen in regard to inducing myometrial contractility of sows. Extended boar semen (80 mL) was supplemented with PGF2alpha (5 mg) for 72 h at 17 +/- 1 degrees C. Cumulative doses of 0.1, 1, 10 and 100 microL of the mixture were tested on uterine strips obtained from diestrus sows. An increase in myometrial contractility was recorded with PGF2alpha supplementation when compared to extended semen or extender treatment alone after 72 h of incubation. Addition of PGF2alpha to the extended boar semen at the time of the experiment did not differ from the 72 h treated group. The results from this study support that PGF2alpha preparations can be added to extended doses of boar semen at processing to enhance myometrial contractility at the time of insemination for up to 72 h.

  14. Similar Odorants Elicit Different Behavioral and Physiological Responses, Some Supersustained

    PubMed Central

    Montague, Shelby A.; Mathew, Dennis; Carlson, John R.

    2011-01-01

    An intriguing question in the field of olfaction is how animals distinguish among structurally similar odorants. We systematically analyzed olfactory responses elicited by a panel of 25 pyrazines. We found that structurally similar pyrazines elicit a wide range of behavioral responses from Drosophila larvae. Each pyrazine was tested against all functional receptors of the larval Odor receptor (Or) repertoire, yielding 525 odorant–receptor combinations. Different pyrazines vary markedly in the responses they elicit from the Or repertoire, with most strong responses deriving from two receptors, Or33b and Or59a. Surprisingly, 2-ethylpyrazine and 2-methylpyrazine, which elicit strikingly similar physiological responses across the receptor repertoire, elicit dramatically different behavioral responses. A small fraction of odorant-receptor combinations elicit remarkably long responses. These responses, which we term “supersustained” responses, are receptor specific and odorant specific, and can last for minutes. Such supersustained responses may prevent olfactory neurons from reporting contemporaneous information about the local odor environment. Odors that elicit such responses could provide a novel means of controlling insect pests and vectors of human disease by impairing the location of human hosts, food sources, and mates. PMID:21613503

  15. Cervical ripening with low-dose prostaglandins in planned vaginal birth after cesarean.

    PubMed

    Schmitz, Thomas; Pourcelot, Anne-Gaelle; Moutafoff, Constance; Biran, Valérie; Sibony, Olivier; Oury, Jean-François

    2013-01-01

    To compare uterine rupture, maternal and perinatal morbidity rates in women with one single previous cesarean after spontaneous onset of labor or low-dose prostaglandin-induced cervical ripening for unfavourable cervix. This was a retrospective cohort study of 4,137 women with one single previous cesarean over a 22-year period. Inpatient prostaglandin administration consisted in single daily local applications. Vaginal delivery was planned for 3,544 (85.7%) patients, 2,704 (76.3%) of whom delivered vaginally (vaginal birth after Cesarean (VBAC) rate = 65.4%). Among women receiving prostaglandins (n=515), 323 (62.7%) delivered vaginally. Uterine rupture (0.7% compared with 0.8%, OR 1.1, 95% CI 0.4-3.4, p=0.88), maternal (0.9% compared with 1.2%, OR 1.3, 95% CI 0.5-3.2, p=0.63) and perinatal (0.3% compared with 0.8%, OR 2.4, 95% CI 0.7-8.5, p=0.18) morbidity rates did not differ significantly between patients with spontaneous onset of labor and those receiving prostaglandins, nor did these rates differ according to the planned mode of delivery. In comparison with patients with spontaneous labor, inducing cervical ripening with low-dose prostaglandins in case of unfavourable cervix is not associated with appreciable increase in uterine rupture, maternal or perinatal morbidity.

  16. Cervical Ripening with Low-Dose Prostaglandins in Planned Vaginal Birth after Cesarean

    PubMed Central

    Schmitz, Thomas; Pourcelot, Anne-Gaelle; Moutafoff, Constance; Biran, Valérie; Sibony, Olivier; Oury, Jean-François

    2013-01-01

    Objectives To compare uterine rupture, maternal and perinatal morbidity rates in women with one single previous cesarean after spontaneous onset of labor or low-dose prostaglandin-induced cervical ripening for unfavourable cervix. Study Design This was a retrospective cohort study of 4,137 women with one single previous cesarean over a 22-year period. Inpatient prostaglandin administration consisted in single daily local applications. Results Vaginal delivery was planned for 3,544 (85.7%) patients, 2,704 (76.3%) of whom delivered vaginally (vaginal birth after Cesarean (VBAC) rate = 65.4%). Among women receiving prostaglandins (n=515), 323 (62.7%) delivered vaginally. Uterine rupture (0.7% compared with 0.8%, OR 1.1, 95% CI 0.4-3.4, p=0.88), maternal (0.9% compared with 1.2%, OR 1.3, 95% CI 0.5-3.2, p=0.63) and perinatal (0.3% compared with 0.8%, OR 2.4, 95% CI 0.7-8.5, p=0.18) morbidity rates did not differ significantly between patients with spontaneous onset of labor and those receiving prostaglandins, nor did these rates differ according to the planned mode of delivery. Conclusion In comparison with patients with spontaneous labor, inducing cervical ripening with low-dose prostaglandins in case of unfavourable cervix is not associated with appreciable increase in uterine rupture, maternal or perinatal morbidity. PMID:24260505

  17. Prostaglandin J2: a potential target for halting inflammation-induced neurodegeneration

    PubMed Central

    Figueiredo-Pereira, Maria E.; Corwin, Chuhyon; Babich, John

    2015-01-01

    Prostaglandins are produced via cyclooxygenases, which are enzymes that play a major role in neuroinflammation. Epidemiological studies show that chronic treatment with low levels of cyclooxygenase inhibitors (NSAIDs) lowers the risk for Alzheimer's (AD) and Parkinson's (PD) diseases by as much as 50%. Unfortunately, inhibiting cyclooxygenases with NSAIDs blocks the synthesis of downstream neuroprotective and neurotoxic prostaglandins, thus producing adverse side effects. We focus on prostaglandin J2 (PGJ2) because it is highly neurotoxic compared to PGA1, D2, and E2. Unlike other prostaglandins, PGJ2 and its metabolites have a cyclopentenone ring with reactive α,β-unsaturated carbonyl groups that form covalent Michael adducts with key cysteines in proteins and GSH. Cysteine-binding electrophiles such as PGJ2 are considered to play an important role in determining whether neurons will live or die. We discuss in vitro and in vivo studies showing that PGJ2 induces pathological processes relevant to neurodegenerative disorders such as AD and PD. Furthermore, we found that increasing intracellular cAMP with the lipophilic peptide PACAP27 counteracts some of the PGJ2-induced detrimental effects. In conclusion, new therapeutic strategies that neutralize the effects of specific neurotoxic prostaglandins downstream from cyclooxygenases could have a significant impact on the treatment of chronic neurodegenerative disorders with fewer adverse side effects. PMID:26748744

  18. Effect of diarachidonin on prostaglandin E2 synthesis in rabbit kidney medulla slices.

    PubMed Central

    Fujimoto, Y; Uno, H; Kagen, C; Ueno, T; Fujita, T

    1985-01-01

    The effect of diarachidonin on the synthesis of prostaglandin E2 in rabbit kidney medulla slices was examined. The addition of diarachidonin stimulated prostaglandin E2 production in a dose-dependent manner. At three concentrations (10, 50 and 100 microM), increases in prostaglandin E2 formation induced by exogenous diarachidonin were 2-fold greater than those induced by exogenous arachidonic acid. Diacylglycerol or phosphatidic acid from egg lecithin had little or no effect on prostaglandin E2 production. Moreover, EGTA failed to inhibit diarachidonin-stimulated prostaglandin E2 formation, indicating that the stimulatory effect of diarachidonin is not mediated through the activation of endogenous phospholipase A2 (including phosphatidic acid-specific phospholipase A2). These results are discussed in the light of our former hypothesis that arachidonic acid release from kidney medulla phospholipids might occur through the sequential action of a phospholipase C coupled to diacylglycerol and monoacylglycerol lipases [Fujimoto, Akamatsu, Hattori & Fujita (1984) Biochem. J. 218, 69-74]. PMID:3937522

  19. The relation between fertility and prostaglandin content of seminal fluid in man.

    PubMed

    Bygdeman, M; Fredricsson, B; Svanborg, K; Samuelsson, B

    1970-08-01

    The relationship of prostaglandin levels in human seminal fluid to fertility, an accepted one, was tested by dividing 150 men into 3 clinical groups: 1) Group A, 29 fertile men; 2) Group B, 100 men in noninvestigated infertile marriages; and 3) Group C, 21 men in infertile marriages with no abnormal clinical or laboratory findings. Thin layer chromatography was used to measure the various prostaglandin compounds, after alkali treatment. Prostaglandin E content of semen samples below 11 mcg/ml was considered low; the percentage of samples in each group displaying this low content was: 0% in A, 17% in B, and 41% in C. The groups of men also differed statistically significantly from each other, with A and C being most highly significant. In all 3 groups, the concentration of 19-hydroxy and dehydrated prostaglandins remained constant. Because Group C members had been studied extensively for causes of infertility, the finding of low prostaglandin E content in seminal fluid compared with controls (A) and noninvestigated infertile male partners (B) shows that the E compounds are important for reproduction.

  20. Emerging drugs to treat glaucoma: targeting prostaglandin F and E receptors.

    PubMed

    Lusthaus, Jed Asher; Goldberg, Ivan

    2016-01-01

    Commercially available prostaglandin analogues (PGAs) activate the prostaglandin F receptor (FP) reducing intraocular pressure (IOP), thereby stabilizing glaucomatous optic neuropathy. Poor adherence with eye drops and intolerance impact treatment success. We review developments in drug formulation and delivery, including punctal plugs, topical ring inserts, subconjunctival injections and inserts, and intraocular inserts. We also outline research into new fixed dose combinations that include prostaglandin analogues and preservative-free versions of established agents. Glaucoma is a chronic, usually progressive disease that causes irreversible visual loss. As its prevalence increases exponentially with age, it has significant implications as the population ages. Health resources need to meet increased demand for glaucoma management resources, including monitoring and treating glaucoma suspects and patients and supporting those who have suffered visual disability. Several promising therapies are under investigation. Sustained-release prostaglandin analogues using alternate delivery methods are encouraging. Delivery routes may be more invasive than topical drops. Nanotechnological-release delivery of prostaglandin analogues could lower IOP effectively. Approaches like this would eliminate many of the adherence issues associated with daily topical PGA eye drop use.

  1. Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor

    PubMed Central

    Gu, Xiaosong; Xu, Jiang; Zhu, Liping; Bryson, Timothy; Yang, Xiao-Ping; Peterson, Edward; Harding, Pamela

    2016-01-01

    Background Prostaglandin E2 (PGE2) EP receptors EP3 and EP4 signal via decreased and increased cAMP production, respectively. Previously we reported that cardiomyocyte-specific EP4 KO mice develop dilated cardiomyopathy with reduced ejection fraction. We thus hypothesized that PGE2 increases contractility via EP4 but decreases contractility via EP3. Methods and Results The effects of PGE2 and the EP1/EP3 agonist sulprostone on contractility were examined in the mouse langendorff preparation and in adult mouse cardiomyocytes (AVM). Isolated hearts of adult male C57Bl/6 mice were perfused with PGE2 (10−6M) or sulp (10−6M) and compared to vehicle. Both PGE2 and sulprostone decreased +dp/dt (p<0.01) and left ventricular developed pressure, LVDP, (p<0.001) with reversal by an EP3 antagonist. In contrast, the EP4 agonist had the opposite effect. AVM contractility was also reduced after treatment with either PGE2 or sulprostone for 10 min. We then examined the acute effects of PGE2, sulprostone and the EP4 agonist on expression of phosphorylated phospholamban (PLN) and SERCA2a in AVM using Western blot. Treatment with either PGE2 or sulprostone decreased expression of phosphorylated PLN corrected to total PLN whereas treatment with the EP4 agonist had the opposite effect. SERCA2a expression was unaffected. Finally, we examined the effect of these compounds in vivo using pressure volume loops. Both PGE2 and sulprostone decreased +dp/dt while the EP4 agonist increased +dp/dt. Conclusions Contractility is reduced via the EP3 receptor but increased via EP4. These effects may be mediated through changes in PLN phosphorylation and has relevance to detrimental effects of inflammation. PMID:27502370

  2. Immunolocalization of a microsomal prostaglandin E synthase in rabbit kidney.

    PubMed

    Fuson, Amanda L; Komlosi, Peter; Unlap, Tino M; Bell, P Darwin; Peti-Peterdi, János

    2003-09-01

    PGE2, the major cyclooxygenase (COX) metabolite of arachidonic acid, is an important paracrine regulator of numerous tubular and vascular functions in the kidney. To date, COX activity has been considered the key step in prostaglandin synthesis and is well characterized. However, much less is known about the recently cloned microsomal PGE2 synthase (mPGES), the terminal enzyme of PGE2 synthesis, which converts COX-derived PGH2 to the biologically important PGE2. Present studies provide the detailed localization of mPGES protein in the rabbit kidney using immunohistochemistry. In the cortex, strong mPGES labeling was found in the macula densa (MD) and principal cells of the connecting segment and cortical collecting tubule but not in intercalated cells. The medulla was abundant in mPGES-positive structures, with heavy labeling in the collecting duct system. In descending thin limbs and renal medullary interstitial cells, mPGES expression was less intense, and it was below the limits of detection in the vasa recta. Expression of MD mPGES, similarly to COX-2, was greatly increased in response to low-salt diet and angiotensin I-converting enzyme inhibition by captopril. These findings suggest autocrine regulation of renal salt and water transport by PGE2 in descending thin limb and collecting tubule and a paracrine effect of PGE2 on the glomerular and medullary vasculature. Similar to other organs, mPGES in the kidney is an inducible enzyme and may be similarly regulated and acts in concert with COX-2.

  3. Modulation of prostaglandin biosynthesis in murine mammary adenocarcinoma tumor cells

    SciTech Connect

    Shalinsky, D.R.

    1988-01-01

    In efforts to exploit the differential oxygen levels within the subcompartments of solid neoplasms, this project has focused on modulating prostaglandin (PG) biosynthesis under aerobic and hypoxic conditions. Mammary adenocarcinoma tumor cells (Line 4526), either intact or sonicated, were incubated with either 2.0 uM {sup 14}C-arachidonic acid (AA) or 20.0 uM {sup 14}C-PGH{sub 2}, respectively. Following metabolism, products were extracted, separated by thin layer chromatography and analyzed by radiochromatographic scan. PGE{sub 2} was predominantly formed with minimal amounts of PGF{sub 2a} or PGD{sub 2}. Indomethacin and ibuprofen inhibited the PGE{sub 2} formation from AA with an IC{sub 50} value of 6.3 {times} 10{sup {minus}8} and 9.6 {times} 10{sup {minus}5}M, respectively. Suspended cells in glass vials were made hypoxic by flushing with N{sub 2} for varying time intervals to study AA metabolism. A time-dependent inhibition of PG biosynthesis was observed under hypoxia, and by 30 min, the PGE{sub 2} synthesis was reduced by 50% which was further inhibited by indomethacin. Misonidazole, a 2-nitroimidazole analogue, partially reversed the inhibition of PGE{sub 2} synthesis under hypoxia by 49% at 100 uM. However, misonidazole did not affect PG biosynthesis under aerobic conditions. The stimulation of PGE{sub 2} biosynthesis by misonidazole under hypoxia was blocked by indomethacin, suggesting that misonidazole can not act independently of the cyclooxygenase.

  4. Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor.

    PubMed

    Gu, Xiaosong; Xu, Jiang; Zhu, Liping; Bryson, Timothy; Yang, Xiao-Ping; Peterson, Edward; Harding, Pamela

    2016-08-01

    Prostaglandin E2 (PGE2) EP receptors EP3 and EP4 signal via decreased and increased cAMP production, respectively. Previously, we reported that cardiomyocyte-specific EP4 knockout mice develop dilated cardiomyopathy with reduced ejection fraction. Thus, we hypothesized that PGE2 increases contractility via EP4 but decreases contractility via EP3. The effects of PGE2 and the EP1/EP3 agonist sulprostone on contractility were examined in the mouse Langendorff preparation and in adult mouse cardiomyocytes. Isolated hearts of adult male C57Bl/6 mice were perfused with PGE2 (10(-6) M) or sulprostone (10(-6) M) and compared with vehicle. Both PGE2 and sulprostone decreased +dp/dt (P<0.01) and left ventricular developed pressure (P<0.001) with reversal by an EP3 antagonist. In contrast, the EP4 agonist had the opposite effect. Adult mouse cardiomyocytes contractility was also reduced after treatment with either PGE2 or sulprostone for 10 minutes. We then examined the acute effects of PGE2, sulprostone, and the EP4 agonist on expression of phosphorylated phospholamban and sarcoendoplasmic reticulum Ca(2+)-ATPase 2a in adult mouse cardiomyocytes using Western blot. Treatment with either PGE2 or sulprostone decreased expression of phosphorylated phospholamban corrected to total phospholamban, whereas treatment with the EP4 agonist had the opposite effect. Sarcoendoplasmic reticulum Ca(2+)-ATPase 2a expression was unaffected. Finally, we examined the effect of these compounds in vivo using pressure-volume loops. Both PGE2 and sulprostone decreased +dp/dt, whereas the EP4 agonist increased +dp/dt. Contractility is reduced via the EP3 receptor but increased via EP4. These effects may be mediated through changes in phospholamban phosphorylation and has relevance to detrimental effects of inflammation. © 2016 American Heart Association, Inc.

  5. Rabbit blastocysts accumulate (/sup 3/H)prostaglandins in vitro

    SciTech Connect

    Jones, M.A.; Harper, M.J.

    1984-08-01

    Rabbit blastocysts obtained on days 5, 6, and 6.8 of pregnancy were incubated in vitro in Tyrode's buffer with /sup 3/H-labeled prostaglandins (PGs). Accumulation of PGs was studied, using Whatman GF/F filters to separate bound and free ligands. The uptake and efflux of (/sup 3/H)PGs were studied as a function of PG type, incubation time, temperature, and effect of metabolic inhibitors as well as age and number of blastocysts. Blastocysts of the same age accumulated approximately the same amount of (/sup 3/H)PGE2 and (/sup 3/H)PGF2 alpha from their environment; however, there was no apparent saturation over a PG concentration range of 1-1000 nM. Both the uptake and efflux of PG were age dependent, with older blastocysts accumulating more PGs. Approximately 90% of the (/sup 3/H)PGs appear to be transported into the blastocoelic fluid, with little PG remaining in the blastomeres. PG accumulation was relatively insensitive to azide, ouabain, cyanide, or bromcresol green, but was affected by incubation at 0 C or the addition of indomethacin (10 micrograms/ml). No catabolism of the accumulated PGs was observed. The release of PGE2 in general did not differ from that of PGF2 alpha, except on day 6.8 of pregnancy when PGE2 was released more rapidly than on day 6. The authors conclude that rabbit blastocysts can accumulate PGs from their environment, which may imply a storage potential in the blastocyst and release before implantation.

  6. Unidirectional transfer of prostaglandin endoperoxides between platelets and endothelial cells.

    PubMed Central

    Schafer, A I; Crawford, D D; Gimbrone, M A

    1984-01-01

    An important determinant of platelet-vessel wall interactions is the local balance of production of endothelial prostacyclin (PGI2) and platelet thromboxane (TX) A2, labile eicosanoids with opposing effects on hemostasis. Disputed evidence suggests that platelet-derived prostaglandin endoperoxide intermediates may be utilized as substrates for vascular PGI2 synthesis. Using several different approaches, we have found that platelets can transfer endoperoxides to cultured endothelial cells for efficient conversion to PGI2, but a reciprocal transfer of endothelial endoperoxides for utilization by platelet thromboxane synthetase does not occur under the same experimental conditions. However, platelets can utilize arachidonic acid released by endothelial cells for lipoxygenase metabolism. We have directly demonstrated the production of [3H]6-keto-PGF1 alpha (the breakdown product of [3H]PGI2) by aspirin-treated endothelial cells in the presence of platelets stimulated with [3H]arachidonic acid. In coincubation experiments using either arachidonate or ionophore A23187 as a stimulus, radioimmunoassay of the net production of arachidonic acid metabolites showed that 6-keto-PGF1 alpha generation by aspirin-treated endothelial cells in the presence of platelets may actually exceed its generation by uninhibited endothelial cells alone. In functional assays, platelet aggregation was inhibited in the presence of aspirin-treated endothelial cells after stimulation with either arachidonate or ionophore A23187. In contrast, the inverse experiments, using aspirin-treated platelets and uninhibited endothelial cells, failed to demonstrate platelet utilization of endothelial endoperoxides for TXA2 production by any of the above methods. These studies thus provide evidence that efficient unidirectional transfer and utilization of platelet-derived endoperoxides for endothelial PGI2 production can occur. This process may serve to amplify PGI2 generation adjacent to areas of vascular

  7. Protease-activated receptors and prostaglandins in inflammatory lung disease

    PubMed Central

    Peters, Terence; Henry, Peter J

    2009-01-01

    Protease-activated receptors (PARs) are a novel family of G protein-coupled receptors. Signalling through PARs typically involves the cleavage of an extracellular region of the receptor by endogenous or exogenous proteases, which reveals a tethered ligand sequence capable of auto-activating the receptor. A considerable body of evidence has emerged over the past 20 years supporting a prominent role for PARs in a variety of human physiological and pathophysiological processes, and thus substantial attention has been directed towards developing drug-like molecules that activate or block PARs via non-proteolytic pathways. PARs are widely expressed within the respiratory tract, and their activation appears to exert significant modulatory influences on the level of bronchomotor tone, as well as on the inflammatory processes associated with a range of respiratory tract disorders. Nevertheless, there is debate as to whether the principal response to PAR activation is an augmentation or attenuation of airways inflammation. In this context, an important action of PAR activators may be to promote the generation and release of prostanoids, such as prostglandin E2, which have well-established anti-inflammatory effects in the lung. In this review, we primarily focus on the relationship between PARs, prostaglandins and inflammatory processes in the lung, and highlight their potential role in selected respiratory tract disorders, including pulmonary fibrosis, asthma and chronic obstructive pulmonary disease. This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 PMID:19845685

  8. Prostaglandin E2 increases the skeletal response to mechanical loading

    NASA Technical Reports Server (NTRS)

    Tang, L. Y.; Cullen, D. M.; Yee, J. A.; Jee, W. S.; Kimmel, D. B.

    1997-01-01

    The study tested the influence of prostaglandin E2 (PGE2) on the skeletal response to increased in vivo mechanical loading through a four-point bending device. One hundred and twenty Sprague-Dawley female rats (6 months old, 354 +/- 34 g) were divided into 12 groups to accommodate all possible combinations of doses of loads (25, 30, or 35 N) and PGE2 (0, 0.1, 0.3, or 1 mg/kg). Rats received subcutaneous injections of PGE2 daily and in vivo loading of the right tibia every Monday, Wednesday, and Friday for four weeks. Histomorphometric analysis of the periosteal and endocortical surfaces following in vivo dual fluorochrome labeling was performed on both the loaded region of the right tibial diaphysis and a similar region of the left tibial diaphysis. Without PGE2, the threshold for loading to stimulate bone formation was 30 N (peak strain 1360 mu epsilon) at the periosteal surface and 25 N (peak strain 580 mu epsilon) at the endocortical surface. Without loading, the minimum dose of PGE2 to stimulate bone formation at all surfaces was 1 mg/kg/day. When 1 mg/kg/day PGE2 was combined with the minimum effective load, an additive effect of PGE2 and loading on bone formation was observed at the endocortical surface, but a synergistic effect was noted at the periosteal surface. No combined effect of ineffective doses of loading and PGE2 was found. A synergistic effect at peak strains of approximately 1625 mu epsilon on the periosteal surface could suggest either the involvement of locally produced growth factors or autoregulation of endogenous synthesis of PGE2 by exogenously administered PGE2.

  9. Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions.

    PubMed

    Pereira, Priscilla Aparecida Tartari; Bitencourt, Claudia da Silva; dos Santos, Daiane Fernanda; Nicolete, Roberto; Gelfuso, Guilherme Martins; Faccioli, Lúcia Helena

    2015-10-12

    Biodegradable lactic-co-glycolic acid (PLGA) microspheres (MS) improve the stability of biomolecules stability and allow enable their sustained release. Lipid mediators represent a strategy for improving host defense; however, most of these mediators, such as prostaglandin D2 (PGD2), have low water solubility and are unstable. The present study aimed to develop and characterize MS loaded with PGD2 (PGD2-MS) to obtain an innovative tool to activate macrophages. PGD2-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process, and the size, zeta potential, surface morphology and encapsulation efficiency were determined. It was also evaluated in vitro the phagocytic index, NF-κB activation, as well as nitric oxide and cytokine production by alveolar macrophages (AMs) in response to PGD2-MS. PGD2-MS were spherical with a diameter of 5.0±3.3 μm and regular surface, zeta potential of -13.4±5.6 mV, and 36% of encapsulation efficiency, with 16-26% release of entrapped PGD2 at 4 and 48 h, respectively. PGD2-MS were more efficiently internalized by AMs than unloaded-MS, and activated NF-κB more than free PGD2. Moreover, PGD2-MS stimulated the production of nitric oxide, TNF-α, IL-1β, and TGF-β, more than free PGD2, indicating that microencapsulation increased the activating effect of PGD2 on cells. In LPS-pre-treated AMs, PGD2-MS decreased the release of IL-6 but increased the production of nitric oxide and IL-1β. These results show that the morphological characteristics of PGD2-MS facilitated interaction with, and activation of phagocytic cells; moreover, PGD2-MS retained the biological activities of PGD2 to trigger effector mechanisms in AMs. It is suggested that PGD2-MS represent a strategy for therapeutic intervention in the lungs of immunocompromised subjects.

  10. Role of prostaglandins in the renal response to calcium infusion.

    PubMed

    Lahera, V; Fiksen-Olsen, M J; Romero, J C

    1990-04-01

    The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca.kg-1.min-1) on renal hemodynamics and on renal excretory function were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 min each (1 ml/min). In a second group, the same doses were administered 30 min after the start of an infusion of prostaglandin (PG) inhibitors (intrarenal indomethacin, 10 micrograms.kg-1.min-1, or intravenous bolus injection of meclofenamate, 5 mg/kg). No change with physiological significance was observed during the infusion of 10 micrograms Ca.kg-1.min-1. However, the infusion of 100 micrograms Ca.kg-1.min-1 induced increases (P less than 0.05) in glomerular filtration rate (50%), sodium excretion rate (180%), and fractional excretion of sodium (160%), with respect to control precalcium values. All these changes were prevented by the concurrent administration of PG synthesis inhibitors. Urinary PGE2 and 6-keto-PGF1 alpha increased 220 and 85%, respectively, during the infusion of 100 micrograms Ca.kg-1.min-1, but both decreased (P less than 0.05) below basal levels during the concurrent administration of PG synthesis inhibitors. The infusion of 100 micrograms Ca.kg-1.min-1 decreased (P less than 0.05) renal blood flow by 16% during the administration of PG synthesis inhibitors. These results suggest that PGs are mediating the increase in hemodynamic and excretory factors induced by the intrarenal infusion of 100 micrograms Ca.kg-1.min-1.

  11. Interleukin-2 deficit in hemodialysis patients. Role of prostaglandins.

    PubMed

    Glez-Gutiérrez, M; de Francisco, A L; Sanz de Castro, S; Ruiz, J C; Prieto, M; García Fuentes, M; Arias, M

    1992-01-01

    Uremic patients suffer from various immunological alterations, whose pathogenesis is still unknown. Here, we studied 37 hemodialysis patients in order to investigate the role of prostaglandins (PGs) in uremic immunological deficiency, specifically in relation to interleukin-2 (IL-2) synthesis. We confirmed previous published data on deficient response to PHA in chronic renal failure patients (cpm, mean +/- SEM: 15,400 +/- 2,100 in uremics vs. 29,500 +/- 3,380 in controls, p < 0.04) and established a correlation between this deficiency and diminished IL-2 synthesis (r = 0.619, p < 0.05). The direct measurement of PGs in lymphocyte cultures showed greatly increased concentrations in the presence of uremic serum (US). We found that PGs synthesis can be inhibited by up to 80% if cultures are supplemented with indomethacin (IND--a cyclooxigenase inhibitor) or by removal of monocytes (producers of PGs). Both methods situated the uremic proliferative response within the normal range in cultures with FCS, and close to the normal range in cultures with US. We observed a deficit of IL-2 in hemodialysis patients (means +/- SD: 8,940 +/- 6,420 in uremics vs. 16,900 +/- 3,890 in controls). Addition of exogenous IL-2 normalized lymphocyte response even in US cultures, with no additive effect between PGs inhibition and exogenous IL-2 except in US cultures. It is suggested that IL-2 deficit of uremics depends, at least in part, on an increase in PGs synthesis induced by US.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Prostaglandin E2 increases the skeletal response to mechanical loading

    NASA Technical Reports Server (NTRS)

    Tang, L. Y.; Cullen, D. M.; Yee, J. A.; Jee, W. S.; Kimmel, D. B.

    1997-01-01

    The study tested the influence of prostaglandin E2 (PGE2) on the skeletal response to increased in vivo mechanical loading through a four-point bending device. One hundred and twenty Sprague-Dawley female rats (6 months old, 354 +/- 34 g) were divided into 12 groups to accommodate all possible combinations of doses of loads (25, 30, or 35 N) and PGE2 (0, 0.1, 0.3, or 1 mg/kg). Rats received subcutaneous injections of PGE2 daily and in vivo loading of the right tibia every Monday, Wednesday, and Friday for four weeks. Histomorphometric analysis of the periosteal and endocortical surfaces following in vivo dual fluorochrome labeling was performed on both the loaded region of the right tibial diaphysis and a similar region of the left tibial diaphysis. Without PGE2, the threshold for loading to stimulate bone formation was 30 N (peak strain 1360 mu epsilon) at the periosteal surface and 25 N (peak strain 580 mu epsilon) at the endocortical surface. Without loading, the minimum dose of PGE2 to stimulate bone formation at all surfaces was 1 mg/kg/day. When 1 mg/kg/day PGE2 was combined with the minimum effective load, an additive effect of PGE2 and loading on bone formation was observed at the endocortical surface, but a synergistic effect was noted at the periosteal surface. No combined effect of ineffective doses of loading and PGE2 was found. A synergistic effect at peak strains of approximately 1625 mu epsilon on the periosteal surface could suggest either the involvement of locally produced growth factors or autoregulation of endogenous synthesis of PGE2 by exogenously administered PGE2.

  13. Prostaglandin E and F2 alpha receptors in human myometrium during the menstrual cycle and in pregnancy and labor

    SciTech Connect

    Giannopoulos, G.; Jackson, K.; Kredentser, J.; Tulchinsky, D.

    1985-12-15

    The binding of prostaglandins E1 and F2 alpha has been studied in the human myometrium and cervix during the menstrual cycle and in the myometrium of pregnant patients at term before and during labor. Tritium-labeled prostaglandin E1 and F2 alpha binding was saturable and reversible. Scatchard analysis of tritium-labeled prostaglandin E1 binding was linear, which suggests a single class of high-affinity binding sites with an estimated apparent equilibrium dissociation constant of 2.5 to 5.4 nmol/L and inhibitor affinities of 0.9, 273, 273, and 217 nmol/L for prostaglandins E2, A1, B1, and F2 alpha, respectively. Scatchard analysis of tritium-labeled prostaglandin F2 alpha, binding was also linear, but the affinity of these binding sites was much lower, with an average dissociation constant of 50 nmol/L and inhibitor affinities of 1.6, 2.2, and 11.2 nmol/L for prostaglandins E1, E2, and A1, respectively. In nonpregnant patients, the concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were similar in the myometrium during the proliferative and secretory phases of the menstrual cycle, but the concentration of these sites was much lower in the cervix. The concentration of the tritium-labeled prostaglandin E1 binding sites was significantly lower in the myometrium of pregnant patients at term than in the myometrium of nonpregnant patients. The concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were not significantly different in the upper and lower myometrium of pregnant patients at term or in the myometrium of such patients before and during labor. The concentrations of the tritium-labeled prostaglandin F2 alpha binding sites during the menstrual cycle and in pregnancy at term were similar to those of tritium-labeled prostaglandin E1 binding sites.

  14. CCSI Risk Estimation: An Application of Expert Elicitation

    SciTech Connect

    Engel, David W.; Dalton, Angela C.

    2012-10-01

    The Carbon Capture Simulation Initiative (CCSI) is a multi-laboratory simulation-driven effort to develop carbon capture technologies with the goal of accelerating commercialization and adoption in the near future. One of the key CCSI technical challenges is representing and quantifying the inherent uncertainty and risks associated with developing, testing, and deploying the technology in simulated and real operational settings. To address this challenge, the CCSI Element 7 team developed a holistic risk analysis and decision-making framework. The purpose of this report is to document the CCSI Element 7 structured systematic expert elicitation to identify additional risk factors. We review the significance of and established approaches to expert elicitation, describe the CCSI risk elicitation plan and implementation strategies, and conclude by discussing the next steps and highlighting the contribution of risk elicitation toward the achievement of the overarching CCSI objectives.

  15. Eliciting knee jerk--a new method of reinforcement.

    PubMed

    Khanal, S; Sainju, R K; Adhikari, P; Thapa, R

    2007-12-01

    This study was designed to detect the sensitivity of different methods of eliciting knee jerks and to compare the conventional methods with the newly purposed maneuver. Knee jerk (a deep tendon reflex) was elicited in 123 apparently normal population (77 males and 46 females) with three different methods (1) without applying reinforcement, (2) applying Jendrassik maneuver (strong voluntary contraction of upper limbs) and (3) using the new method of reinforcement--that is by dorsiflexion of ankle joint of the same foot voluntarily as strong as possible on which the jerk would be elicitated. The sensitivity of the method without reinforcement was found to be is 87.8%; that with Jendrassik maneuver was 93.5%, whereas the sensitivity of newly proposed maneuver was 99.2%. Results of the present study have served to demonstrate that elicitation of knee jerk with newly proposed reinforcement maneuver is the best among all three methods.

  16. Picturing Masculinities: Using Photo-elicitation in Men's Health Research.

    PubMed

    Creighton, Genevieve M; Brussoni, Mariana; Oliffe, John L; Han, Christina

    2015-10-18

    This article explores the use of photo-elicitation methods in two men's health studies. Discussed are the ways that photo-elicitation can facilitate conversation about health issues that might be otherwise challenging to access. In the first study, researchers explored 35 young men's experiences of grief following the accidental death of a male peer. In the second study, researchers describe 64 fathers' perceptions about their roles and identity with respect to child safety and risk. Photographs and accompanying narratives were analyzed and results were theorized using a masculinities framework. Discussed are the benefits of photo-elicitation, which include facilitating conversation about emotions, garnering insight into the structures and identities of masculinity in the context of men's health. Considered also are some methodological challenges amid recommendations for ensuring reflexive practices. Based on the findings it is concluded that photo-elicitation can innovatively advance qualitative research in men's health.

  17. Knowledge Elicitation: Phase 1 Final Report. Volume 1

    DTIC Science & Technology

    1989-06-01

    artificial intelligence has been focused on methods for eliciting and representing expert knowledge (e.g., Newell and Simon, 1972; Schank and Abelson...methods. These issues have not yet been dealt with in a satisfactory way, either in the artificial intelligence community or by cognitive psychologists...ELICITATION 2.1 The Myth of "Mining for Nugets" of Knowledge The central question in the field of artificial intelligence, whether computers can be

  18. Paradoxical reactions elicited by diazepam in children with classic autism.

    PubMed

    Marrosu, F; Marrosu, G; Rachel, M G; Biggio, G

    1987-01-01

    Administration of diazepam (10 mg i.m.) to seven children (two girls and five boys) affected by infantile autism elicited paradoxical behavioural responses. Mainly, anxiogenic effect, unsocialized aggressive behaviour and explosive aggression were dramatically increased in comparison with the same symptoms present before and after treatment. The results show for the first time that benzodiazepines may elicit paradoxical behavioural response in autistic children. The possible involvement of an altered function at the level of GABA/benzodiazepine receptor complex is discussed.

  19. Protein thiol modification by 15-deoxy-Delta12,14-prostaglandin J2 addition in mesangial cells: role in the inhibition of pro-inflammatory genes.

    PubMed

    Sánchez-Gómez, Francisco J; Cernuda-Morollón, Eva; Stamatakis, Konstantinos; Pérez-Sala, Dolores

    2004-11-01

    The cyclopentenone prostaglandin and PPARgamma agonist 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) displays anti-inflammatory effects in several experimental models. Direct modification of protein thiols is arising as an important mechanism of cyclopentenone prostaglandin action. However, little is known about the extent or specificity of this process. Mesangial cells (MC) play a key role in glomerulonephritis. In this work, we have studied the selectivity of protein modification by 15d-PGJ(2) in MC, and the correlation with the modulation of several proinflammatory genes. MC incubation with biotinylated 15d-PGJ(2) results in the labeling of a distinct set of proteins as evidenced by two-dimensional electrophoresis. 15d-PGJ(2) binds to nuclear and cytosolic targets as detected by fluorescence microscopy and subcellular fractionation. The pattern of biotinylated 15d-PGJ(2)-modified polypeptides is readily distinguishable from that of total protein staining or labeling with biotinylated iodoacetamide. 15d-PGJ(2) addition requires the double bond in the cyclopentane ring. 9,10-Dihydro-15d-PGJ(2), a 15d-PGJ(2) analog that shows the same potency as peroxisome proliferator-activated receptor (PPAR) agonist in MC but lacks the cyclopentenone moiety, displays reduced ability to modify proteins and to block 15d-PGJ(2) binding. Micromolar concentrations of 15d-PGJ(2) inhibit cytokine-elicited levels of inducible nitricoxide synthase, cyclooxygenase-2, and intercellular adhesion molecule-1 in MC. In contrast, 9,10-dihydro-15d-PGJ(2) does not reproduce this inhibition. 15d-PGJ(2) effect is not blocked by the PPARgamma antagonist 2-chloro-5-nitro-N-phenylbenzamide (GW9662). Moreover, compounds possessing an alpha,beta-unsaturated carbonyl group, like 2-cyclopenten-1-one and 2-cyclohexen-1-one, reduce pro-inflammatory gene expression. These observations indicate that covalent modification of cellular thiols by 15d-PGJ(2) is a selective process that plays an important

  20. Elicitation of natural language representations of uncertainty using computer technology

    SciTech Connect

    Tonn, B.; Goeltz, R.; Travis, C.; Tennessee Univ., Knoxville, TN )

    1989-01-01

    Knowledge elicitation is an important aspect of risk analysis. Knowledge about risks must be accurately elicited from experts for use in risk assessments. Knowledge and perceptions of risks must also be accurately elicited from the public in order to intelligently perform policy analysis and develop and implement programs. Oak Ridge National Laboratory is developing computer technology to effectively and efficiently elicit knowledge from experts and the public. This paper discusses software developed to elicit natural language representations of uncertainty. The software is written in Common Lisp and resides on VAX Computers System and Symbolics Lisp machines. The software has three goals, to determine preferences for using natural language terms for representing uncertainty; likelihood rankings of the terms; and how likelihood estimates are combined to form new terms. The first two goals relate to providing useful results for those interested in risk communication. The third relates to providing cognitive data to further our understanding of people's decision making under uncertainty. The software is used to elicit natural language terms used to express the likelihood of various agents causing cancer in humans and cancer resulting in various maladies, and the likelihood of everyday events. 6 refs., 4 figs., 4 tabs.

  1. Expert elicitation and the problem of detecting undeclared activities

    SciTech Connect

    Pilat, Joseph F.; Sylvester, K. B.; Stanbro, W. D.

    2002-01-01

    Measures applicable to the detection of undeclared activities are not well established, and their effectiveness is uncertain. To detect clandestine paths, the IAEA is still developing processes and procedures. As the Agency gains experience with new measures and with integrated safeguards, dealing with such problems may become more experience-based and perhaps more closely parallel the process with current safeguards where detection probabilities for the measures to be utilized on declared paths are well characterized. Whether or not this point will be reached for undeclared and mixed paths, the only tool that appears suitable at present for the purpose of generating a reasonable detection probability that can over time be tested against reality and, if necessary, adjusted is formal expert judgment, or expert elicitation. Formal expert elicitation is a structured process that makes use of people knowledgeable in certain areas to make assessments. To provide a 'proof of principle' of this methodology for presentation to the Agency, experts in nuclear technology, nonproliferation, safeguards and open source information, as well as in formal expert elicitation processes, engaged in three illustrative expert elicitations on assessing information analysis as a means to detect undeclared activities. These elicitations were successful. This paper will discuss the process of and issues raised by the elicitations.

  2. Prostaglandin receptor EP2 is responsible for cyclooxygenase-2 induction by prostaglandin E2 in mouse skin.

    PubMed

    Ansari, Kausar M; Sung, You Me; He, Guobin; Fischer, Susan M

    2007-10-01

    The EP2 prostanoid receptor is one of the four subtypes of receptors for prostaglandin E2 (PGE2). We previously reported that deletion of EP2 led to resistance to chemically induced mouse skin carcinogenesis, whereas overexpression of EP2 resulted in enhanced tumor development. The purpose of this study was to investigate the underlying molecular mechanisms. We found that EP2 knockout mice had reduced cyclooxygenase-2 (COX-2) expression after 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment compared with wild-type (WT) mice. Further, primary keratinocytes from EP2 transgenic mice had increased COX-2 expression after either TPA or PGE2 treatment and COX-2 expression was blocked by 10 microM SQ 22,536, an adenylate cyclase inhibitor. EP2 knockout mice had significantly decreased, whereas EP2 transgenic mice had significantly increased PGE2 production in response to a single treatment of TPA. Cyclic AMP response element-binding protein (CREB) phosphorylation was elevated to a greater extent in keratinocytes from EP2 transgenic mice compared with those of WT mice following PGE2 treatment. A protein kinase A (PKA) inhibitor reduced PGE2-mediated CREB phosphorylation in keratinocytes from EP2 transgenic mice. Furthermore, we found that there was no CREB phosphorylation in EP2 knockout mice following PGE2 treatment. PGE2-induced DNA synthesis (cell proliferation) was significantly decreased in keratinocytes from EP2 knockout mice following pretreatment with 10 microM SQ 22,536. Taken together, EP2 activation of the PKA/CREB-signaling pathway is responsible for keratinocyte proliferation and our findings reveal a positive feedback loop between COX-2 and PGE2 that is mediated by the EP2 receptor.

  3. Prostaglandin E2 in human placenta: its vascular effects and activation of prostaglandin E2 formation by nicotine and cotinine.

    PubMed

    Rama Sastry, B V; Hemontolor, M E; Olenick, M

    1999-02-01

    Tobacco smoking by pregnant women increases the frequency of spontaneous abortions and preterm births. Human labor is associated with enhanced intrauterine phospholipid metabolism and production of prostaglandin E2 (PGE2) which induces labor, initiates uterine contractions and maintains the homeostasis of placental blood flow. Therefore, we studied: (a) the influence of nicotine and cotinine on the effects of PGE2 on placental vasculature in perfused human placental cotyledon, and (b) the activation of placental phospholipase A2 (PLA2) by nicotine and cotinine using 1-palmitoyl-2-[1-14C]arachidonyl-phosphatidylethanolamine (PE, 2.2 nmol) as substrate. These studies revealed that: (1) increasing concentrations of PGE2 (10- 150 ng/ml) increased umbilical perfusion pressure by 170 +/- 10% (n = 6) of control (100%). Cotinine (2 microg/ml) enhanced this effect at all concentrations of PGE2. Nicotine (2 microg/ml) prevented the effect of PGE2; (2) both cotinine (EC50 470-500 fmol/l) and nicotine (EC50 18-32 pmol/l) activated PLA2 in human placental tissues. These observations indicated that cotinine was more potent than in nicotine activating PLA2 and potentiating the vasoconstrictive effects of PGE2 on fetal placental circulation. Nicotine activates nicotinic receptors and releases placental acetylcholine, a vasodilator of placental arteries. Acetylcholine stimulates muscarinic receptors of endothelial cells resulting in the release of endothelium-derived relaxing factor (EDRF), and possibly nitric oxide. Therefore, nicotine prevents or abolishes the vasoconstrictive effects of PGE2 through the release of EDRF. Cotinine is inactive at nicotinic and muscarinic receptors. Therefore, accumulation of cotinine, the major metabolite of nicotine, in fetal circulation may contribute to production of PGE2 and induction of preterm labor and spontaneous abortions.

  4. High-Throughput Quantification of Bioactive Lipids by MALDI Mass Spectrometry: Application to Prostaglandins

    PubMed Central

    Manna, Joseph D.; Reyzer, Michelle L.; Latham, Joey C.; Weaver, C. David; Marnett, Lawrence J.; Caprioli, Richard M.

    2011-01-01

    Analysis and quantification of analytes in biological systems is a critical component of metabolomic investigations of cell function. The most widely used methods employ chromatographic separation followed by mass spectrometric analysis, which requires significant time for sample preparation and sequential chromatography. We introduce a novel high-throughput, separation-free methodology based on MALDI mass spectrometry that allows for the parallel analysis of targeted metabolomes. Proof-of-concept is demonstrated by analysis of prostaglandins and glyceryl prostaglandins. Derivatization to incorporate a charged moiety into ketone-containing prostaglandins dramatically increases the signal-to-noise ratio relative to underivatized samples. This resulted in an increased dynamic range (15 fmol – 2000 fmol on plate) and improved linearity (r2= 0.99). The method was adapted for high-throughput screening methods for enzymology and drug discovery. Application to cellular metabolomics was also demonstrated. PMID:21770391

  5. Stretch-induced prostaglandins and protein turnover in cultured skeletal muscle

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.; Hatfaludy, Sophia; Sohar, Istvan; Shansky, Janet

    1990-01-01

    The purpose of the study is to determine whether mechanical stimulation of cultured muscle cells influences prostaglandin efflux rates and whether they are related to stretch-induced alterations in protein turnover rates. The materials and methods of the experiment, including cell cultures, mechanical stimulation, protein synthesis, and degradation assays are outlined, and emphasis is placed on the effect of short-term mechanical stimulation in basal medium prostaglandin efflux from cultured skeletal muscle and stretch-induced alterations in prostaglandins efflux in complete medium. The major finding of the study is that mechanical stimulation of tissue-cultured skeletal-muscle cells under conditions inducing skeletal-muscle hypertropy increases the efflux of PGE(2) and PGE(2-alpha) but not 6-keto-PGF(1-alpha), the prostacyclin product.

  6. Acute effect of prostaglandins and somatostatin on thymidine uptake of gastric mucosa cells

    SciTech Connect

    Alino, S.F.; Hilario, E. )

    1988-12-01

    This study compares the in vivo effect of exogenous administration of prostaglandin E2 (30 {mu}g/kg) and its precursor, arachidonic acid (30 {mu}g/kg), with the effect of indomethacin (5 mg/kg) on the 6-({sup 3}H)thymidine uptake of antral mucosa of mice by autoradiographical methods. Likewise, the effect of somatostatin (30 {mu}g/kg) on 6-({sup 3}H)thymidine uptake is studied. Evaluation of the number of labeled cells, in the histological sections of the gastric mucosa, showed that arachidonic acid, prostaglandin E2, and somatostatin induced an increase in the number of labeled cells (107, 44, and 45%, respectively), while indomethacin induced a decrease of 32% compared to the control group. These results suggest that prostaglandins may mediate stimulatory effects on thymidine uptake of gastric mucosa cells in the first step after drug administration.

  7. TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration.

    PubMed

    Zhang, Yongyou; Desai, Amar; Yang, Sung Yeun; Bae, Ki Beom; Antczak, Monika I; Fink, Stephen P; Tiwari, Shruti; Willis, Joseph E; Williams, Noelle S; Dawson, Dawn M; Wald, David; Chen, Wei-Dong; Wang, Zhenghe; Kasturi, Lakshmi; Larusch, Gretchen A; He, Lucy; Cominelli, Fabio; Di Martino, Luca; Djuric, Zora; Milne, Ginger L; Chance, Mark; Sanabria, Juan; Dealwis, Chris; Mikkola, Debra; Naidoo, Jacinth; Wei, Shuguang; Tai, Hsin-Hsiung; Gerson, Stanton L; Ready, Joseph M; Posner, Bruce; Willson, James K V; Markowitz, Sanford D

    2015-06-12

    Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.

  8. The effect of prostaglandin inhibition on the development of pulmonary pathology associated with dead Dirofilaria immitis.

    PubMed

    Tarish, J H; Atwell, R B

    1993-09-01

    Flunixin meglumine was used to examine the effect of prostaglandin inhibition on the pathogenesis of Dirofilaria immitis in the pulmonary arteries of dogs. Immunopathological reactions to dead filariae were monitored by light and transmission electron microscopy and serology. Lung lesions in prostaglandin-inhibited dogs exposed to dead filariae were enhanced compared to control dogs. This was associated with the persistence of parasitic antigen in lung tissue and in the blood. Serology demonstrated that after insertion of D. immitis in treated dogs, antibody levels did not change, while immune complex and antigen levels increased. These results indicate that prostaglandin may have a protective effect on the way the lung reacts to dead D. immitis, and that altered dynamics of the antigen processing may well contribute to the associated lung lesions.

  9. Effect of exogenous ovarian steroids on the uterine luminal prostaglandins in ovariectomised mares with experimental endometritis.

    PubMed

    Watson, E D; Stokes, C R; Bourne, F J

    1988-05-01

    Prostaglandins (PGs) F and E2 were measured in lavage fluid from the uterus of ovariectomised mares after experimental induction of uterine inflammation. Treatment with progesterone alone, or progesterone followed by oestradiol, significantly increased the concentrations of these PGs in the lavage compared with mares treated with oestradiol or control mares. Ovarian steroids, therefore, influenced uterine PG synthesis in response to an inflammatory stimulus. To determine whether the uterine lavage procedure might contribute to the concentrations of prostaglandins in the lavage, the procedure was also performed on six intact mares. With the exception of washings obtained at luteolysis, uterine concentrations of PGF (measured as the plasma metabolite 15-keto-13,14-dihydro PGF2 alpha) had returned to prewashing levels within 30 minutes of the start of uterine lavage. Lavage was therefore unlikely to have influenced the concentrations of prostaglandins in the lavage fluid.

  10. Comparison of prostaglandin F2alpha and hypertonic saline for induction of midtrimester abortion.

    PubMed

    Lauersen, N H; Wilson, K H; Beling, C G; Fuchs, F

    1974-12-01

    20 healthy women between 18-20 weeks of gestation and seeking abortion were studied to compare the effects of prostaglandin F2alpha (PGF2) with those of instillation of saline solution and intravenous oxytocin. 9 out of 10 patients in the prostaglandin group aborted completely in about 15.16 hours. In only one of the prostaglandin patients did abortion have to be completed surgically. All of the 10 patients in the saline solution-oxytocin group also aborted completely, but with a mean time of 22.34 hours, a difference not statistically significant. The complication rate was higher in patients aborted with PGF2, including postabortion lactation and gastrointestinal effects, especially vomiting. In terms of hormonal changes, the similarities between the 2 groups were more numerous than the differences, suggesting that the 2 mechanics of abortion may not be totally different. Comparative studies on a much larger group of patients are desirable.

  11. [Evaluation of the use of prostaglandins E2 in cervical maturation].

    PubMed

    Loria Casanova, M; Lemus Maichel, M; Kably Ambe, A

    1989-07-01

    This is a prospective study in order to know the efficacy of prostaglandin E2 gel in the induction of labor by intravaginal administration at the Instituto Nacional de Perinatología. All pregnancies had between 16 and 34 weeks of gestation. There were two groups: Group A (n = 40) patients in whom the induction was made with prostaglandin plus oxitocin, and Group B (n = 40) when just oxitocin was employed. In the first group it was shown a shortening in the length of time of induction, hospitalization days and resolution of the pregnancy by vaginal route in the 100% of the cases. We did not observed side effects in relation to the use of the prostaglandin.

  12. Stretch-induced prostaglandins and protein turnover in cultured skeletal muscle

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.; Hatfaludy, Sophia; Sohar, Istvan; Shansky, Janet

    1990-01-01

    The purpose of the study is to determine whether mechanical stimulation of cultured muscle cells influences prostaglandin efflux rates and whether they are related to stretch-induced alterations in protein turnover rates. The materials and methods of the experiment, including cell cultures, mechanical stimulation, protein synthesis, and degradation assays are outlined, and emphasis is placed on the effect of short-term mechanical stimulation in basal medium prostaglandin efflux from cultured skeletal muscle and stretch-induced alterations in prostaglandins efflux in complete medium. The major finding of the study is that mechanical stimulation of tissue-cultured skeletal-muscle cells under conditions inducing skeletal-muscle hypertropy increases the efflux of PGE(2) and PGE(2-alpha) but not 6-keto-PGF(1-alpha), the prostacyclin product.

  13. Estrus synchronization and controlled breeding in goats using prostaglandin F(2)alpha.

    PubMed

    Ogunbiyi, P O; Molokwu, E C; Sooriyamoorthy, T

    1980-04-01

    Estrus synchronization in the goat employing the double injection regimen of 7.5 mg of prostaglandin F(2)alpha (Lutalyse) at each injection, resulted in 64% and 84% synchronization at first and second injections, respectively. Breeding at estrus induced by the second injection resulted in 90% conception. Kidding at the end of the gestation period was spread over a 17-day period. The first and the last does had 141 and 158 days of gestation, respectively. The findings of this study indicate that two injections of prostaglandin F(2)alpha 10 days apart is superior to a single injection for estrus synchronization in the goat. Breeding following the second injection resulted in high conception rate. Due to individual differences in gestational lengths, estrus synchronization with prostaglandin F(2)alpha cannot be depended upon for synchrony of kidding.

  14. A Michaelis-Menten-style model for the autocatalytic enzyme prostaglandin H synthase.

    PubMed

    Tien, Joseph H; Hazelton, William D; Sparks, Rachel; Ulrich, Cornelia M

    2005-07-01

    Prostaglandin H synthase (PGHS) is an autocatalytic enzyme which plays a key role in the arachidonic acid metabolic pathway. PGHS mediates the formation of prostaglandin H2, the precursor for a number of prostaglandins which are important in a wide variety of biological processes, including inflammation, blood clotting, renal function, and tumorigenesis. Here we present a Michaelis-Menten-style model for PGHS. A stability analysis determines when the reaction becomes self-sustaining, and can help explain the regulation of PGHS activity in vivo. We also consider a quasi-steady-state approximation (QSSA) for the model, and present conditions under which the QSSA is expected to be a good approximation. Applying the QSSA for this model can be useful in computationally intensive modeling endeavors involving PGHS.

  15. The EP1 receptor for prostaglandin E2 promotes the development and progression of malignant murine skin tumors

    PubMed Central

    Surh, Inok; Rundhaug, Joyce E.; Pavone, Amy; Mikulec, Carol; Abel, Erika; Simper, Melissa; Fischer, Susan M.

    2011-01-01

    High levels of prostaglandin E2 (PGE2) synthesis resulting from the upregulation of COX-2 has been shown to be critical for the development of non-melanoma skin tumors. This effect of PGE2 is likely mediated by one or more of its 4 G-protein coupled membrane receptors, EP1–4. A previous study showed that BK5.EP1 transgenic mice produced more carcinomas than wild type (WT) mice using initiation/promotion protocols, although the tumor response was dependent on the type of tumor promoter used. In this study, a single topical application of either 7,12-dimethylbenz[a]anthracene (DMBA) or benzo[a]pyrene (B[a]P), alone, was found to elicit squamous cell carcinomas (SCC) in the BK5.EP1 transgenic mice, but not in WT mice. While the epidermis of both WT and transgenic mice was hyperplastic several days after DMBA, this effect regressed in the WT mice while proliferation continued in the transgenic mice. Several parameters associated with carcinogen initiation were measured and were found to be similar between genotypes, including CYP1B1 and aromatase expression, B[a]P adduct formation, Ras activity and keratinocyte stem cell numbers. However, EP1 transgene expression elevated COX-2 levels in the epidermis and SCC could be completely prevented in DMBA-treated BK5.EP1 mice either by feeding the selective COX-2 inhibitor celecoxib in their diet or by crossing them onto a COX-2 null background. These data suggest that the tumor promoting/progressing effects of EP1 require the PGE2 synthesized by COX-2. PMID:21739481

  16. Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans.

    PubMed

    Cheng, Kang; Wu, Tsuei-Ju; Wu, Kenneth K; Sturino, Claudio; Metters, Kathleen; Gottesdiener, Keith; Wright, Samuel D; Wang, Zhaoyin; O'Neill, Gary; Lai, Eseng; Waters, M Gerard

    2006-04-25

    Nicotinic acid (NA) is commonly used to treat dyslipidemia, but it elicits an adverse effect, termed flushing, which consists of cutaneous vasodilation with associated discomfort. An animal model of NA-induced flushing has been established in mice. As in humans, NA stimulated vasodilation in a dose-dependent manner, was associated with an increase of the vasodilatory prostaglandin (PG) D2 in plasma and could be blocked by pretreatment with aspirin. Two PGD2 receptors have been identified: PGD2 receptor 1 (DP1, also called DP) and PGD2 receptor 2 (DP2, sometimes termed CRTH2). DP2 does not mediate NA-induced vasodilation; the DP2-specific agonist DK-PGD2 (13,14-dihydro-15-keto-PGD2) did not induce cutaneous vasodilation, and DP2-/- mice had a normal vasodilatory response to NA. By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD2- and NA-induced vasodilation. NA-induced vasodilation was also studied in DP1+/+, DP1+/-, and DP1-/- mice; although NA-induced vasodilation depended almost completely on DP1 in female mice, it depended only partially on DP1 in male mice. The residual NA-induced vasodilation in male DP-/- mice was aspirin-sensitive. Thus, in the mouse, DP1 appears to be an important component involved in NA-induced vasodilation, but other cyclooxygenase-dependent mechanisms also may be involved. A clinical study in healthy men and women demonstrated that treatment with MK-0524 reduced the symptoms of flushing and the increase in skin perfusion after the administration of NA. These studies suggest that DP1 receptor antagonism may be an effective means to suppress NA-induced flushing in humans.

  17. Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans

    PubMed Central

    Cheng, Kang; Wu, Tsuei-Ju; Wu, Kenneth K.; Sturino, Claudio; Metters, Kathleen; Gottesdiener, Keith; Wright, Samuel D.; Wang, Zhaoyin; O’Neill, Gary; Lai, Eseng; Waters, M. Gerard

    2006-01-01

    Nicotinic acid (NA) is commonly used to treat dyslipidemia, but it elicits an adverse effect, termed flushing, which consists of cutaneous vasodilation with associated discomfort. An animal model of NA-induced flushing has been established in mice. As in humans, NA stimulated vasodilation in a dose-dependent manner, was associated with an increase of the vasodilatory prostaglandin (PG) D2 in plasma and could be blocked by pretreatment with aspirin. Two PGD2 receptors have been identified: PGD2 receptor 1 (DP1, also called DP) and PGD2 receptor 2 (DP2, sometimes termed CRTH2). DP2 does not mediate NA-induced vasodilation; the DP2-specific agonist DK-PGD2 (13,14-dihydro-15-keto-PGD2) did not induce cutaneous vasodilation, and DP2−/− mice had a normal vasodilatory response to NA. By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD2- and NA-induced vasodilation. NA-induced vasodilation was also studied in DP1+/+, DP1+/−, and DP1−/− mice; although NA-induced vasodilation depended almost completely on DP1 in female mice, it depended only partially on DP1 in male mice. The residual NA-induced vasodilation in male DP−/− mice was aspirin-sensitive. Thus, in the mouse, DP1 appears to be an important component involved in NA-induced vasodilation, but other cyclooxygenase-dependent mechanisms also may be involved. A clinical study in healthy men and women demonstrated that treatment with MK-0524 reduced the symptoms of flushing and the increase in skin perfusion after the administration of NA. These studies suggest that DP1 receptor antagonism may be an effective means to suppress NA-induced flushing in humans. PMID:16617107

  18. A Heterogeneous Mixture of F-Series Prostaglandins Promotes Sperm Guidance in the Caenorhabditis elegans Reproductive Tract

    PubMed Central

    Hoang, Hieu D.; Prasain, Jeevan K.; Dorand, Dixon; Miller, Michael A.

    2013-01-01

    The mechanisms that guide motile sperm through the female reproductive tract to oocytes are not well understood. We have shown that Caenorhabditis elegans oocytes synthesize sperm guiding F-series prostaglandins from polyunsaturated fatty acid (PUFA) precursors provided in yolk lipoprotein complexes. Here we use genetics and electrospray ionization tandem mass spectrometry to partially delineate F-series prostaglandin metabolism pathways. We show that omega-6 and omega-3 PUFAs, including arachidonic and eicosapentaenoic acids, are converted into more than 10 structurally related F-series prostaglandins, which function collectively and largely redundantly to promote sperm guidance. Disruption of omega-3 PUFA synthesis triggers compensatory up-regulation of prostaglandins derived from omega-6 PUFAs. C. elegans F-series prostaglandin synthesis involves biochemical mechanisms distinct from those in mammalian cyclooxygenase-dependent pathways, yet PGF2α stereoisomers are still synthesized. A comparison of F-series prostaglandins in C. elegans and mouse tissues reveals shared features. Finally, we show that a conserved cytochrome P450 enzyme, whose human homolog is implicated in Bietti's Crystalline Dystrophy, negatively regulates prostaglandin synthesis. These results support the model that multiple cyclooxygenase-independent prostaglandins function together to promote sperm motility important for fertilization. This cyclooxygenase-independent pathway for F-series synthesis may be conserved. PMID:23382703

  19. [Ecbolic and hormonal action of synthetic prostaglandin F2a in fetal mummification in two Holstein cows (author's transl)].

    PubMed

    Guay, P; Lamothe, P

    1979-02-01

    Ecbolic and Hormonal Action of Synthetic Prostaglandin F(2)a in Fetal Mummification in Two Holstein CowsThe effects of treatment with synthetic prostaglandin F(2)a (500mug i.m.) to correct cases of fetal mummification in two Holstein cows are described.

  20. An audit about labour induction, using prostaglandin, in women with a scarred uterus.

    PubMed

    Cogan, Alexandra; Barlow, Patricia; Benali, Nordine; Murillo, Daniel; Manigart, Yannick; Belhomme, Julie; Rozenberg, Serge

    2012-12-01

    Induction of labour after a previous caesarean section is still controversial. We aim to analyse, in a population of women who have a uterine scar, the maternal, foetal and neonatal complications in relation to the mode of labour and delivery. Retrospective analysis of collected data from all the singleton deliveries of patients with a scarred uterus (N=798), admitted to the hospital between August 2006 and March 2009. maternal and perinatal complications. Among 798 singleton deliveries, 36.1% had a spontaneous labour, 12.6% a prostaglandin-induced labour and 2.9% an ocytocin-induced labour, and 48.4% had an elective caesarean section. The chance of delivering vaginally was respectively 84.4% for those who had a spontaneous labour, 75.2% for those who were induced using prostaglandin, 82.6% after induction using ocytocin. There were eight uterine ruptures, four after spontaneous labour (1.4%), two after prostaglandin induction (2%) and two at the time of an iterative caesarean section (0.5%). There were no differences between groups, except the risk of haemorrhage (17.4% after spontaneously induced labour, 34.8% after ocytocin, 17.8% after prostaglandin and 44.6% after iterative caesarean section; p<0.005) and the neonatal admissions when analysed by intention to treat only (8.3% after spontaneously induced labour, 9.1% after ocytocin, 12% after prostaglandin and 16.8% after iterative caesarean section; p<0.009). Although no increase in maternal or perinatal outcome was observed in relation to prostaglandin-induced labour after caesarean section, this study is too underpowered to exclude an increased risk.

  1. [Causes of labor initiation in man: role of oxytocin and prostaglandins].

    PubMed

    Husslein, P

    1985-01-01

    Questions related to the mechanism of human labor are of central clinical importance nowadays, since the majority of perinatal mortality and morbidity is due to disregulation of uterine contractility mainly premature onset of labor. During delivery of spontaneous or induced onset endogenous prostaglandin F-synthesis increases dramatically and reaches a maximum at the time of placental separation. These increased amounts of prostaglandin F and E lead to myometrial contractions and to a reduction of the cervical resistance. Post partum, prostaglandins lead to the contracture of the myometrium necessary for separation and expulsion of the placenta. The precise causes for initiation of parturition at term however have not been fully elucidated. The present review presents a theory in which oxytocin acts as central trigger of labor. At the end of human pregnancy a marked rise in the concentration of oxytocin receptors in the myometrium can be observed, thereby leading to an increased sensitivity of the myometrium towards oxytocin. Therefore, a small increase of the circulating oxytocin concentration in the maternal peripheral blood (for example through addition of fetal oxytocin) is sufficient to induce contractions. Apart from inducing contractions, oxytocin also leads to a stimulation of prostaglandin synthesis through receptors in the decidua. Prostaglandins themselves lead to further contractions, soften the cervix, induce gap-junctions and sensitize the myometrium further for oxytocin, thereby leading to a progressive cervical dilatation. At the end of the first stage of labor, the membranes usually rupture leading to a further increase in prostaglandin synthesis, so that the mechanism can no longer be interrupted exogenously.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Hyperthyroidism advances luteolysis in the pregnant rat through changes in prostaglandin balance.

    PubMed

    Navas, Paola B; Motta, Alicia B; Hapon, María B; Jahn, Graciela A

    2011-10-01

    To investigate the underlying mechanisms implicated in the premature luteolysis induced by hyperthyroidism in pregnant rats. Experimental basic study. Research institute. Groups of 6-8 adult female Wistar rats were injected SC daily with T(4) (0.25 mg/kg) or vehicle, starting 8 days before mating, and killed by decapitation on days 19 (G19), 20 (G20), and 21 (G21) of pregnancy. Corpora lutea and truncal blood of control and hyperthyroid rats were obtained. Circulating and intraluteal hormones were determined by using RIA and luteal messenger RNA (mRNA) expression of enzymes and factors involved in P synthesis and metabolism by reverse transcriptase-polymerase chain reaction. 20α-Hydroxysteroid dehydrogenase (20αHSD) mRNA and protein expression was also determined by quantitative reverse transcriptase-polymerase chain reaction and Western blot. Hyperthyroidism advanced luteolysis and 20αHSD expression induction by one day without changes in enzymes involved in P synthesis, decreased circulating E(2) and luteal estrogen receptor beta, and increased luteal prostaglandin F(2α) on G19 and G20 and prostaglandin E(2) on G19, while decreasing it on G20. Thus, decreased estrogenic influence and high prostaglandin F(2α)/prostaglandin E(2) ratio favors premature induction of 20αHSD on hyperthyroid rats. Hyperthyroidism affects luteolysis in pregnant rats through alterations in luteal prostaglandin balance and decreased luteotrophic factors favoring the luteolytic action of prostaglandin F(2α) that induces premature 20αHSD expression that in turn advances circulating P fall and delivery. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term.

    PubMed

    Thomas, Jane; Fairclough, Anna; Kavanagh, Josephine; Kelly, Anthony J

    2014-06-19

    Prostaglandins have been used for induction of labour since the 1960s. This is one of a series of reviews evaluating methods of induction of labour. This review focuses on prostaglandins given per vaginam, evaluating these in comparison with placebo (or expectant management) and with each other; prostaglandins (PGE2 and PGF2a); different formulations (gels, tablets, pessaries) and doses. 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). We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 March 2014) and bibliographies of relevant papers. Clinical trials comparing vaginal prostaglandins used for third trimester cervical ripening or labour induction with placebo/no treatment, with each other, or other methods listed above it on a predefined list of labour induction methods. We assessed studies and extracted data independently. Seventy randomised controlled trials (RCTs) (11,487 women) are included. In this update seven new RCTs (778 women) have been added. Two of these new trials compare PGE2 with no treatment, four compare different PGE2 formulations (gels versus tablets, or sustained release pessaries) and one trial compares PGF2a with placebo. The majority of trials were at unclear risk of bias for most domains.Overall, vaginal prostaglandin E2 compared with placebo or no treatment probably reduces the likelihood of vaginal delivery not being achieved within 24 hours. The risk of uterine hyperstimulation with fetal heart rate changes is increased (4.8% versus 1.0%, risk ratio (RR) 3.16, 95% confidence interval (CI) 1.67 to 5.98, 15 trials, 1359 women). The caesarean section rate is probably reduced by about 10% (13.5% versus 14.8%, RR 0.91, 95% CI 0.81 to 1.02, 36 trials, 6599 women). The overall effect on improving maternal and fetal outcomes (across a variety of measures

  4. Roles of prostaglandins and nitric oxide in the effect of endothelin-1 on renal hemodynamics.

    PubMed

    Lin, H; Smith, M J; Young, D B

    1996-09-01

    It is known that endothelin-1 stimulates the release of nitric oxide and prostaglandins in various vascular beds. We designed the present study to analyze the roles of prostaglandins and nitric oxide in the effect of endothelin-1 on the regulation of renal hemodynamics and renin release. We used N omega-nitro-L-arginine methyl ester (L-NAME) and meclofenamic acid to inhibit the production of nitric oxide and prostaglandins, respectively. With a nonfiltering kidney model, renal blood flow was reduced 21% in dogs treated with L-NAME and 18% in dogs treated with meclofenamic acid. Inhibition of nitric oxide and prostaglandins, however, produced opposite effects on estimated glomerular hydraulic pressure: L-NAME increased glomerular hydraulic pressure from 63.1 +/- 0.9 to 64.6 +/- 1.3 mm Hg (P < .01), and meclofenamic acid reduced glomerular hydraulic pressure from 63.3 +/- 1.4 to 59.8 +/- 1.6 mm Hg (P < .01). Endothelin-1 infusion produced a dose-dependent reduction in renal blood flow after blockade of nitric oxide and prostaglandins. The responses of glomerular hydraulic pressure were different in the two groups during endothelin-1 infusion. Endothelin-1 progressively reduced glomerular hydraulic pressure in a dose-dependent fashion in the meclofenamic acid group. However, endothelin-1 slightly increased glomerular hydraulic pressure until the infusion rate reached 5.0 ng/kg per minute. At that rate, endothelin-1 reduced glomerular hydraulic pressure from 63.3 +/- 1.4 to 47.0 +/- 1.4 mm Hg in the meclofenamic acid group (P < .01), a more than 25% reduction, whereas at the same dose, endothelin-1 reduced glomerular hydraulic pressure only less than 2% in the L-NAME group. In addition, blockade of nitric oxide and prostaglandins did not alter the inhibitory effect of endothelin-1 on renin release in the non-filtering kidney. Therefore, the present study demonstrates that the release of nitric oxide and prostaglandins might modulate the effects of endothelin-1 on the

  5. [Intracavernous injections of prostaglandin E1 in the treatment of erection disorders].

    PubMed

    Beretta, G; Zanollo, A; Portalupi, W

    1991-12-01

    Vasoactive drugs have been widely used for the treatment of impotence in the last years. Recently Prostaglandin E1 has been employed with success as a therapy in erection problems. The Authors have treated with Prostaglandin E1 209 patients complaining erection failure. Positive results were obtained in 155 patients (74,16%). No complications or side effects occurred. 129 patients of the 155 in which the test resulted positive were proposed a self-injection program and 115 accepted. Until now no side effects or complications occurred.

  6. Skin graft hypertrichosis associated with prostaglandin analog in the treatment of glaucoma.

    PubMed

    Shafi, Fariha; Madge, Simon N

    2014-01-01

    Prostaglandin analogs are commonly used in the treatment of glaucoma. They are a safe and effective treatment associated with few side effects. Common local side effects include conjunctival hyperemia, iris pigmentation, and eyelash hypertrichosis. The authors present a case of a patient using travoprost treatment for primary open-angle glaucoma, who underwent excision of a lower eyelid basal cell carcinoma and reconstruction with an upper eyelid tarsoconjunctival flap and overlying skin graft. The patient developed hypertrichosis of the skin graft attributable to prostaglandin analog use.

  7. The effects of sulfasalazine on human male fertility potential and seminal prostaglandins.

    PubMed

    Cosentino, M J; Chey, W Y; Takihara, H; Cockett, A T

    1984-10-01

    Fertility parameters of 10 men with chronic inflammatory bowel disease under treatment with sulfasalazine for at least 5 years were compared to those of 19 control subjects. Seminal parameters examined included ejaculate volume, sperm number and concentration, sperm motility index, sperm viability, pH, zinc concentration, prostaglandins E and F2-alpha, prolactin and 7 classes of sperm morphology. In addition, plasma concentrations of follicle-stimulating hormone, luteinizing hormone, testosterone and prolactin were noted. The data indicate that sulfasalazine therapy reduces semen quality and that this effect can be reversed upon removal from therapy. This reversal is independent of seminal prostaglandin concentrations.

  8. Melittin stimulates liver glycogenolysis and the release of prostaglandin D2 and thromboxane B2.

    PubMed Central

    García-Sáinz, J A; Hernández-Sotomayor, S M; Macías-Silva, M

    1990-01-01

    Melittin stimulates glycogenolysis and induces vasoconstriction in perfused rat liver. The effect was rapid and associated with production and release of prostaglandin D2 and thromboxane B2. Indomethacin blocked the release of these eicosanoids and the stimulation of glycogenolysis induced by melittin. Ibuprofen blocked the release of prostaglandin D2 induced by melittin and markedly attenuated that of thromboxane B2. Interestingly, the initial burst of glucose output induced by melittin was not inhibited by ibuprofen, although the duration of the glycogenolytic action of the peptide was greatly diminished. PMID:2375756

  9. The Management of Prostaglandin-controlled Breeding Programs in Beef Cattle — A Five Year Study

    PubMed Central

    Wenkoff, M.; Crowe-Swords, P. R.

    1983-01-01

    A herd of 180 beef cows was synchronized with prostaglandin and bred by artifical insemination for five successive years. Factors influencing the success or failure of estrus synchronizing programs were identified, including the management of nutrition, postpartum interval, cow age and artificial insemination technology. Specific recommendations on the management of prostaglandin-controlled breeding programs resulted in improving the pregnancy rates from 33% in year 1 to 67% in year 5. Improved management and close veterinary supervision were shown to improve the success of an estrus synchronization program. PMID:17422223

  10. Theophylline prevents the inhibitory effect of prostaglandin E2 on glucose-induced insulin secretion in man.

    PubMed

    Giugliano, D; Cozzolino, D; Salvatore, T; Giunta, R; Torella, R

    1988-06-01

    This study was undertaken to assess the mechanism by which prostaglandins of the E series inhibit glucose-induced insulin secretion in man. Acute insulin response (mean change 3-10 min) to iv glucose (0.33 g/kg) was decreased by 40% during the infusion of prostaglandin E2 (10 micrograms/min) and glucose disappearance rates were reduced (P less than 0.05). Insulin response to arginine (5 g iv) and tolbutamide (1 g iv) were not affected by the same rate of prostaglandin E2 infusion. The inhibitory effect of prostaglandin E2 on glucose-induced insulin secretion was prevented by theophylline (100 mg as a loading dose followed by a 5 mg/min infusion), a drug that increases the intracellular cAMP concentrations by inhibiting phosphodiesterase activity. Our data suggest the involvement of the adenylate cyclase system in the inhibitory action of prostaglandin E2 on glucose-induced insulin secretion in man.

  11. Fructose overload modifies vascular morphology and prostaglandin production in rats.

    PubMed

    Puyó, A M; Mayer, M A; Cavallero, S; Donoso, A S; Peredo, H A

    2004-04-01

    1. A fructose (Fru)-enriched diet induces a mild increase in blood pressure associated with hyperglycaemia, hypertriglyceridaemia, and insulin resistance, resembling the human 'syndrome X', being an useful model to study hypertension and type 2 diabetes. 2. A sustained elevation of blood pressure is associated with cardiovascular structural modifications such as left ventricular hypertrophy and increased wall thickness:lumen diameter ratio in blood vessels. 3. Prostanoids (PR), metabolites of arachidonic acid through the cyclooxygenase pathway, include vasoactive substances synthesized and released by the vessel walls. 4. The aim of the present study was to analyse, in Fru-treated rats: (i) the morphology of mesenteric vessels and; (ii) the PR production in aorta and mesenteric vessels, in order to assess whether these parameters are related with the haemodynamic alterations observed in this experimental model. 5. Blood pressure, glycaemia and triglyceridaemia, were significantly elevated in both (4 and 22 weeks) Fru-treated groups. Meanwhile body and heart weight as well as insulinaemia were similar between experimental animals and controls. 6. The mesenteric vessels of Fru-treated rats (22 weeks) showed an increased thickness and area of the media when compared with the controls; meanwhile, the lumen diameter was similar in both groups. 7. The Fru treatment for 4 weeks did not modify PR production in aorta, whereas in the mesenteric bed it diminished prostaglandin (PG) E(2) release significantly compared with the controls. However, in the group treated for 22 weeks, Fru reduced PGI(2) production in the aorta, as assessed by 6-keto-PGF(1)alpha measurements. Meanwhile, in the mesenteric bed, the chronic Fru treatment decreased PGE(2) release but, rather surprisingly, increased the output of PGI(2) when compared with its corresponding controls. 8. In conclusion, the present study shows the existence of an alteration in the morphology of mesenteric vessels in Fru

  12. Bioprocess optimization of furanocoumarin elicitation by medium renewal and re-elicitation: a perfusion-based approach.

    PubMed

    Diwan, Renuka; Malpathak, Nutan

    2011-03-01

    Effect of various abiotic (methyl jasmonate, salicylic acid) and biotic (yeast extract, Aspergillus niger) elicitors on furanocoumarin production and in situ product removal was studied using shoot cultures of Ruta graveolens L. Elicitation by yeast extract (1% w/v) on day 15 was most effective. It led to 7.8-fold higher furanocoumarin production that was attained 24 h after elicitation and 43% of the product was released into the medium. Changes in the relative concentration of furanocoumarins produced depend on the elicitor used. Molar ratio of bergapten increased to 93% in response to yeast extract. With the perspective of developing a commercially feasible process, an approach for preserving viability of biomass and its reuse needs to be developed. For this, medium renewal strategy was investigated. Removal of the spent medium 48 h after elicitation allowed in situ product removal and proved effective in revival of cultures, allowing reuse of biomass. A week after medium renewal, the revived biomass was re-elicited and a second furanocoumarin production peak was obtained. A perfusion-based bioprocess optimization approach, employing elicitation coupled with medium renewal with subsequent re-elicitation, as a new strategy for improved furanocoumarin production, has been suggested.

  13. Evaluation of WO 2012/177618 A1 and US-2014/0179750 A1: novel small molecule antagonists of prostaglandin-E2 receptor EP2.

    PubMed

    Ganesh, Thota

    2015-07-01

    Recent studies underscore that prostaglandin-E2 exerts mostly proinflammatory effects in chronic CNS and peripheral disease models, mainly through a specific prostanoid receptor EP2. However, very few highly characterized EP2 receptor antagonists have been reported until recently, when Pfizer and Emory University published two distinct classes of EP2 antagonists with good potency, selectivity and pharmacokinetics. The purpose of this article is to evaluate recently published patents WO 2012/177618 A1 and US-2014/0179750 A1 from Emory, which describe a number of cinnamic amide- and amide-derivatives as a potent antagonists of EP2 receptor, and their neuroprotective effects in in vitro and in an in vivo model. A selected compound from this patent(s) also attenuates prostate cancer cell growth and invasion in vitro, suggesting these compounds should be developed for therapeutic use.

  14. Elicitation of structure-specific antibodies by epitope scaffolds

    PubMed Central

    Ofek, Gilad; Guenaga, F. Javier; Schief, William R.; Skinner, Jeff; Baker, David; Wyatt, Richard; Kwong, Peter D.

    2010-01-01

    Elicitation of antibodies against targets that are immunorecessive, cryptic, or transient in their native context has been a challenge for vaccine design. Here we demonstrate the elicitation of structure-specific antibodies against the HIV-1 gp41 epitope of the broadly neutralizing antibody 2F5. This conformationally flexible region of gp41 assumes mostly helical conformations but adopts a kinked, extended structure when bound by antibody 2F5. Computational techniques were employed to transplant the 2F5 epitope into select acceptor scaffolds. The resultant “2F5-epitope scaffolds” possessed nanomolar affinity for antibody 2F5 and a range of epitope flexibilities and antigenic specificities. Crystallographic characterization of the epitope scaffold with highest affinity and antigenic discrimination confirmed good to near perfect attainment of the target conformation for the gp41 molecular graft in free and 2F5-bound states, respectively. Animals immunized with 2F5-epitope scaffolds showed levels of graft-specific immune responses that correlated with graft flexibility (p < 0.04), while antibody responses against the graft—as dissected residue-by-residue with alanine substitutions—resembled more closely those of 2F5 than sera elicited with flexible or cyclized peptides, a resemblance heightened by heterologous prime-boost. Lastly, crystal structures of a gp41 peptide in complex with monoclonal antibodies elicited by the 2F5-epitope scaffolds revealed that the elicited antibodies induce gp41 to assume its 2F5-recognized shape. Epitope scaffolds thus provide a means to elicit antibodies that recognize a predetermined target shape and sequence, even if that shape is transient in nature, and a means by which to dissect factors influencing such elicitation. PMID:20876137

  15. Cytokine-induced prostaglandin E2 production and cyclooxygenase-2 expression in dental pulp cells: downstream calcium signalling via activation of prostaglandin EP receptor.

    PubMed

    Chang, M-C; Chen, Y-J; Tai, T-F; Tai, M-R; Li, M-Y; Tsai, Y-L; Lan, W-H; Wang, Y-L; Jeng, J-H

    2006-10-01

    To determine whether (i) proinflammatory cytokines stimulate prostaglandin E(2) (PGE(2)) production and cyclooxygenase (COX) gene expression in dental pulp cells, and (ii) pulp cells that express different prostaglandin E(2) receptor (EP) isoforms and their activation by PGE(2) leads to downstream Ca(2+) signalling. Cultured human dental pulp cells were exposed to interleukin (IL)-1beta and tumour necrotic factor-alpha (TNF-alpha). The expression of COX-1 and COX-2 was measured with reverse transcriptase-polymerase chain reaction (RT-PCR). The production of PGE(2) was measured using an enzyme-linked immunosorbent assay. Expression of prostaglandin EP receptor isoforms was studied by RT-PCR, whereas fura-2 fluorescence was used to measure calcium mobilization. The Kruskal-Wallis test and Wilcoxon sum rank test with Bonferroni correction were used for statistical analysis. Interleukin-1beta and TNF-alpha stimulate PGE(2) production of human dental pulp cells (P < 0.05). IL-1beta stimulated the COX-2 but not COX-1 mRNA expression. Pulp cells express mainly EP2, EP3 and EP1 receptors as analysed by RT-PCR. PGE(2) (0.25-2 micromol L(-1)) stimulated the Ca(2+) mobilization as indicated by increase in fura-2 fluorescence. Interleukin-1beta and TNF-alpha may stimulate PGE(2) production in dental pulp cells. Activation of prostaglandin EP receptors in dental pulp cells by PGE(2) may induce Ca(2+) signalling to regulate cellular biological activity during inflammation.

  16. Prostaglandins induce early growth response 1 transcription factor mediated microsomal prostaglandin E2 synthase up-regulation for colorectal cancer progression

    PubMed Central

    Stamatakis, Konstantinos; Jimenez-Martinez, Marta; Jimenez-Segovia, Alba; Chico-Calero, Isabel; Conde, Elisa; Galán-Martínez, Javier; Ruiz, Julia; Pascual, Alejandro; Barrocal, Beatriz; López-Pérez, Ricardo; García-Bermejo, María Laura; Fresno, Manuel

    2015-01-01

    Cyclooxygenase2 (COX2) has been associated with cell growth, invasiveness, tumor progression and metastasis of colorectal carcinomas. However, the downstream prostaglandin (PG)-PG receptor pathway involved in these effects is poorly characterized. We studied the PG-pathway in gene expression databases and we found that PTGS2 (prostaglandin G/H synthase and cyclooxygenase) and PTGES (prostaglandin E synthase) are co-expressed in human colorectal tumors. Moreover, we detected that COX2 and microsomal Prostaglandin E2 synthase 1 (mPGES1) proteins are both up-regulated in colorectal human tumor biopsies. Using colon carcinoma cell cultures we found that COX2 overexpression significantly increased mPGES1 mRNA and protein. This up-regulation was due to an increase in early growth response 1 (EGR1) levels and its transcriptional activity. EGR1 was induced by COX2-generated PGF2α. A PGF2α receptor antagonist, or EGR1 silencing, inhibited the mPGES1 induction by COX2 overexpression. Moreover, using immunodeficient mice, we also demonstrated that both COX2- and mPGES1-overexpressing carcinoma cells were more efficient forming tumors. Our results describe for the first time the molecular pathway correlating PTGS2 and PTGES in colon cancer progression. We demonstrated that in this pathway mPGES1 is induced by COX2 overexpression, via autocrine PGs release, likely PGF2α, through an EGR1-dependent mechanism. This signaling provides a molecular explanation to PTGS2 and PTGES association and contribute to colon cancer advance, pointing out novel potential therapeutic targets in this oncological context. PMID:26498686

  17. Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term.

    PubMed

    Kelly, A J; Kavanagh, J; Thomas, J

    2003-01-01

    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. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. 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). The Cochrane Pregnancy and Childbirth Group trials register (May 2003) and bibliographies of relevant papers. 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. A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. In total, 101 studies were considered: 43 excluded and 57 (10,039 women) included. One study is awaiting assessment. Vaginal prostaglandin E2 compared with placebo or no treatment reduced the likelihood of vaginal delivery not being achieved within 24 hours (18% versus 99%, relative risk (RR) 0.19, 95% confidence interval (CI) 0.14 to 0.25, 2 trials, 384 women), there was no evidence of a difference between caesarean section rates although the risk of uterine hyperstimulation with fetal heart rate changes was increased (4.6% versus 0.51%, RR 4.14, 95% CI 1.93 to 8.90, 13 trials, 1203 women). Comparison of vaginal prostaglandin F2a with placebo showed similar caesarean section rates but the cervical score was more likely to be improved (15% versus 60%, RR 0.25, 95% CI 0.13 to 0.49, 5 trials, 467 women), and the risk of oxytocin

  18. Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term.

    PubMed

    Kelly, A J; Kavanagh, J; Thomas, J

    2001-01-01

    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. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. 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). The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled trials register and bibliographies of relevant papers. Last searched: November 2000. The criteria for inclusion included the following: (1) 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; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. A strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally, and incorporated into a series of primary reviews arranged by methods of induction of labour, following a standardised methodology. The data was then extracted from the primary reviews into a series of secondary reviews, arranged by category of woman. To avoid duplication of data in the primary

  19. Does aberrant expression of cyclooxygenase-2 and prostaglandin-E2 receptor genes lead to abortion in Chlamydia trachomatis-infected women.

    PubMed

    Singh, Namita; Prasad, Priya; Kumar, Praveen; Singh, Laishram Chandreshwar; Das, Banashree; Rastogi, Sangita

    2016-03-01

    The aim of the study was to characterize the expression of cyclooxygenase-2 (COX-2) and prostaglandin-E2 (PGE2) genes in spontaneously aborted tissues from women infected with Chlamydia trachomatis. A total of 135 spontaneous aborters (Group I) and 45 induced aborters (controls; Group II) attending Obstetrics and Gynaecology Department at Safdarjung hospital (New Delhi, India), were enrolled. Polymerase chain reaction (PCR) assay was performed to detect C. trachomatis DNA in endometrial curettage tissue (ECT). Differential expression of COX-2 and PGE2 receptors at mRNA level was analysed in ECT using reverse transcription PCR and real-time PCR. In total, 14.8% patients were diagnosed as C. trachomatis-positive in Group I whereas all control patients were C. trachomatis-negative. Qualitative expression of COX-2 (p < 0.05) and PGE2 (p < 0.0001) receptors was found increased in C. trachomatis-positive patients (Group I) in comparison to controls. Quantitative real-time PCR analysis also showed upregulation in transcript levels of both COX-2 (p < 0.002) and PGE2 (p < 0.0001) receptors in infected patients (Group I) versus Group II. COX-2 and PGE2 expression was higher (p < 0.002) in recurrent spontaneous aborters in comparison to sporadic spontaneous aborters. Results suggest that chlamydial infection leads to upregulation of COX-2 in C. trachomatis-positive recurrent spontaneous aborters, which probably mediates increased prostaglandin synthesis.

  20. The Appearance of Phosphenes Elicited Using a Suprachoroidal Retinal Prosthesis.

    PubMed

    Sinclair, Nicholas C; Shivdasani, Mohit N; Perera, Thushara; Gillespie, Lisa N; McDermott, Hugh J; Ayton, Lauren N; Blamey, Peter J

    2016-09-01

    Phosphenes are the fundamental building blocks for presenting meaningful visual information to the visually impaired using a bionic eye device. The aim of this study was to characterize the size, shape, and location of phosphenes elicited using a suprachoroidal retinal prosthesis. Three patients with profound vision loss due to retinitis pigmentosa were implanted with a suprachoroidal electrode array, which was used to deliver charge-balanced biphasic constant-current pulses at various rates, amplitudes, and durations to produce phosphenes. Tasks assessing phosphene appearance, location, overlap, and the patients' ability to recognize phosphenes were performed using a custom psychophysics setup. Phosphenes were reliably elicited in all three patients, with marked differences in the reported appearances between patients and between electrodes. Phosphene shapes ranged from simple blobs to complex forms with multiple components in both space and time. Phosphene locations within the visual field generally corresponded to the retinotopic position of the stimulating electrodes. Overlap between phosphenes elicited from adjacent electrodes was observed with one patient, which reduced with increasing electrode separation. In a randomized recognition task, two patients correctly identified the electrode being stimulated for 57.2% and 23% of trials, respectively. Phosphenes of varying complexity were successfully elicited in all three patients, indicating that the suprachoroidal space is an efficacious site for electrically stimulating the retina. The recognition scores obtained with two patients suggest that a suprachoroidal implant can elicit phosphenes containing unique information. This information may be useful when combining phosphenes into more complex and meaningful images that provide functional vision.

  1. Cortical activity elicited by isolated vowels and diphthongs.

    PubMed

    Mäkelä, A M; Alku, P; May, P J C; Mäkinen, V; Tiitinen, H

    2004-11-30

    Cortical activity underlying speech perception has been studied mostly by using isolated vowels with constant formant frequencies. Speech, however, is characterized by formant transitions whereby formant frequencies change as a function of time. We used magnetoencephalography (MEG) to investigate cortical activity elicited by isolated vowels and diphthongs containing formant transitions. Ten subjects were presented with two isolated vowels /a/ and /u/ and diphthongs /au/ and /ua/. Stimulus duration was 200 ms, and the diphthongs started and ended with a 50-ms constant-formant period and included a 100-ms linear transition period. Apart from studying the auditory N100m response, we examined subsequent brain activity in a 500-ms poststimulus time window, as the transitions were expected to elicit activity also in later stages of cognitive processing. All the stimuli elicited prominent N100m responses. Thereafter, both the isolated vowels and diphthongs elicited sustained brain activity lasting up to 500 ms. The present observations indicate that identification of the speech sounds as well as changes in their identity are reflected in the auditory N100m. Notably, the stimuli appeared to elicit left-hemispheric activity resembling the N400, typically obtained by using more complicated speech stimuli such as words and sentences.

  2. [The physiological importance of prostaglandins in the mechanism of human labor].

    PubMed

    Husslein, P

    1982-10-29

    Recent results indicate that prostaglandins play a major role in the mechanism of human labor. There are, however, no systematic studies on the role of prostaglandins in various forms of induction of labor. In the present study the concentration of 13,14-dihydro,15-ketoprostaglandin F2 (PGFM) in the maternal peripheral plasma was determined in labor of spontaneous onset, in labor after induction with oxytocin and in labor after induction by artificial rupture of membranes (ARM). In an additional group of women PGFM was determined before and immediately after delivery to get an insight into the mechanism of placental separation. In labor of spontaneous onset PGFM concentration increased significantly. In labour induced by oxytocin PGFM levels rose only in those women in whom induction of labor was successful. In induction of labor by ARM, PGFM level also increased in all women in whom induction was successful. At the time of placental separation PGFM concentration in the maternal blood increased dramatically. From the result of this study it is concluded that the increase of prostaglandin F synthesis is a necessary prerequisite for vaginal delivery and that prostaglandins are of major importance in the mechanism of placental separation and expulsion.

  3. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons.

    PubMed

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun; Park, Yong Seek; Park, Cheung-Seog; Jin, Young-Ho

    2015-01-02

    Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E2 (PGE2) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE2 induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE2 effect on visceral afferent sensory neurons of the rat. Interestingly, PGE2 itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE2-induced potentiation were blocked by a selective E-prostanoid type 4 (EP4) receptors antagonist, L-161,982, but type 1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE2 effects. PGE2 induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE2 potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin synthetase inhibitors by selectively targeting EP4 receptor/PKA pathway without interrupt prostaglandin synthesis.

  4. Novel prostaglandin receptor modulators--part II: EP receptor modulators; a patent review (2002 - 2012).

    PubMed

    Flesch, Daniel; Merk, Daniel; Lamers, Christina; Schubert-Zsilavecz, Manfred

    2013-02-01

    Prostaglandins and their G-protein-coupled receptors play numerous physiological and pathophysiological roles, especially in inflammation and its resolution. The variety of effects mediated by prostanoids makes prostanoid receptors valuable drug targets and the research on prostaglandin receptor modulators is intensive. The physiological and pathophysiological effects of prostaglandin E(2) are especially complex and numerous. The four subtypes of EP receptor have gained a lot of industrial and academic interest, in particular EP(2) and EP(4) for various indications. Evaluation of the patent activity over the last decade (2002 - 2012) illustrates several potent compounds targeting the distinct prostaglandin E(2) receptors. Many novel methods for the use of EP receptor modulators have been developed, in addition to the classical indications for agents modulating the arachidonic acid cascade such as pain and inflammation. Several EP targeting agents with good potency and selectivity have been developed but their pharmacological use and utility has not yet been satisfactorily investigated. More research is necessary, and clinical use of these agents might therefore take some more time.

  5. Neutrophil activation: an alternative to prostaglandin inhibition as the mechanism of action for NSAIDs.

    PubMed

    Altman, R D

    1990-02-01

    Experimental findings suggest that inhibition of neutrophil activation rather than suppression of prostaglandin formation may represent the principal mechanism of action of antiinflammatory drugs. This theory would account for the effectiveness of prostaglandin preserving agents, such as the nonacetylated salicylate salsalate, in the treatment of rheumatic disease. Results of the controlled clinical trials described in other papers contained in this supplement indicate that salsalate is equally effective as aspirin and the newer NSAID naproxen in relieving the signs and symptoms of rheumatoid arthritis. The damage to the gastric mucosa associated with NSAID use is believed to be attributable to impairment of mucosal defense mechanisms resulting from the inhibition of gastroprotective prostaglandins. Confirmation of neutrophil activation as the mechanism of action of NSAIDs would explain the efficacy of salsalate in light of its lower incidence of gastrointestinal side effects in controlled clinical trials with aspirin and naproxen. Establishment of such a mechanism would also suggest that the other adverse effects related to prostaglandin inhibition, such as hypersensitivity reactions, platelet dysfunction, and a reduction in renal function, are not necessary correlates of effective antiinflammatory therapy.

  6. Prostaglandin signaling regulates nephron segment patterning of renal progenitors during zebrafish kidney development

    PubMed Central

    Poureetezadi, Shahram Jevin; Cheng, Christina N; Chambers, Joseph M; Drummond, Bridgette E; Wingert, Rebecca A

    2016-01-01

    Kidney formation involves patterning events that induce renal progenitors to form nephrons with an intricate composition of multiple segments. Here, we performed a chemical genetic screen using zebrafish and discovered that prostaglandins, lipid mediators involved in many physiological functions, influenced pronephros segmentation. Modulating levels of prostaglandin E2 (PGE2) or PGB2 restricted distal segment formation and expanded a proximal segment lineage. Perturbation of prostaglandin synthesis by manipulating Cox1 or Cox2 activity altered distal segment formation and was rescued by exogenous PGE2. Disruption of the PGE2 receptors Ptger2a and Ptger4a similarly affected the distal segments. Further, changes in Cox activity or PGE2 levels affected expression of the transcription factors irx3b and sim1a that mitigate pronephros segment patterning. These findings show for the first time that PGE2 is a regulator of nephron formation in the zebrafish embryonic kidney, thus revealing that prostaglandin signaling may have implications for renal birth defects and other diseases. DOI: http://dx.doi.org/10.7554/eLife.17551.001 PMID:27996936

  7. Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn't the stomach digest itself?

    PubMed

    Wallace, John L

    2008-10-01

    Except in rare cases, the stomach can withstand exposure to highly concentrated hydrochloric acid, refluxed bile salts, alcohol, and foodstuffs with a wide range of temperatures and osmolarity. This is attributed to a number of physiological responses by the mucosal lining to potentially harmful luminal agents, and to an ability to rapidly repair damage when it does occur. Since the discovery in 1971 that prostaglandin synthesis could be blocked by aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), there has been great interest in the contribution of prostaglandins to gastric mucosal defense. Prostaglandins modulate virtually every aspect of mucosal defense, and the importance of this contribution is evident by the increased susceptibility of the stomach to injury following ingestion of an NSAID. With chronic ingestion of these drugs, the development of ulcers in the stomach is a significant clinical concern. Research over the past two decades has helped to identify some of the key events triggered by NSAIDs that contribute to ulcer formation and/or impair ulcer healing. Recent research has also highlighted the fact that the protective functions of prostaglandins in the stomach can be carried out by other mediators, in particular the gaseous mediators nitric oxide and hydrogen sulfide. Better understanding of the mechanisms through which the stomach is able to resist injury in the presence of luminal irritants is helping to drive the development of safer anti-inflammatory drugs, and therapies to accelerate and improve the quality of ulcer healing.

  8. O6.09PROSTAGLANDIN E RECEPTOR-4 ACTIVATION REGULATES TRYPTOPHAN METABOLISM IN HUMAN MALIGNANT GLIOMAS

    PubMed Central

    Ochs, K.; Ott, M.; Rauschenbach, K.J.; Sahm, F.; Opitz, C.A.; von Deimling, A.; Wick, W.; Platten, M.

    2014-01-01

    Malignant gliomas generate a local immunosuppressive microenvironment as well as systemic immunosuppression. Tryptophan-2,3-dioxygenase (TDO)-mediated tryptophan metabolism and the production of immunosuppressive prostaglandins relevantly contribute to this inhibition of anti-glioma immune responses. We now connect these two critical immunosuppressive pathways by demonstrating that prostaglandins enhance TDO expression and enzymatic activity in malignant gliomas via activation of prostaglandin E receptor-4 (EP4). Stimulation with prostaglandin E2 (PGE2) concentration-dependently upregulates TDO-mediated kynurenine release in human glioma cell lines, while knockdown of the PGE2 receptor EP4 inhibits TDO expression and activity. In tissue of human malignant gliomas expression of the PGE2-producing enzyme cyclooxygenase-2 (COX-2) and its receptor EP4 are associated with TDO expression both on transcript and protein level. Of clinical relevance, high expression of EP4 correlates with poor survival in patients with gliomas of the WHO grades III and IV. Importantly, treatment of glioma cells with an EP4 inhibitor decreased TDO expression and activity. In summary targeting EP4 may inhibit both immunosuppressive COX-2 signaling as well as tryptophan degradation and thus could provide a novel immunotherapeutic avenue for the treatment of malignant gliomas.

  9. Insect anti-viral immunity: roles of prostaglandins and other eicosanoids

    USDA-ARS?s Scientific Manuscript database

    Insect/microbe relationships are very complex, with an array of signaling systems acting in surveillance, detection and responses to the presence of microbes. We report that prostaglandins (PGs) are responsible for essential signaling in activating and coordinating insect innate immune reactions to ...

  10. Do antiglaucomatous prostaglandins induce melanogenesis in human conjunctiva?: an impression cytology pilot study.

    PubMed

    Cagigrigoriu, Andrea; Boero, Elena; Carenini, Alessandra Boles; Rolle, Teresa; Cappia, Susanna; Bacillo, Elisa; Papotti, Mauro; Gregori, Dario; Brovarone, Filippo Vitale; Grignolo, Federico Maria

    2010-01-01

    To determine the effect of antiglaucomatous prostaglandin analogs on conjunctival melanogenesis. For this pilot study, 30 glaucomatous patients treated with prostaglandin drops (alone and in association to beta-blockers) and 30 control subjects (15 healthy volunteers and 15 patients treated with beta-blockers) were included in this transversal, single masked, case-control, observational study. Skin complexion, eye color, conjunctival pigmentation, lacrimal tests, and corneal fluorescein staining were evaluated. Immunoreactivity for Tyrosinase was assayed on conjunctival imprints. Twenty percent of patients treated with prostaglandins and 10% of the control subjects clinically manifested conjunctival pigmentation (P=0.279). Only 4% (8/198) of the conjunctival specimens were positive to Tyrosinase immunostaining, with no statistically significant difference among the groups (P=0.449). In all cases, the proportion of positive cells was below 4%. When compared with subjects having negative specimens, those with positive immunostains did not show any statistically significant difference in skin complexion, eye color or exposure to irritants, and ultraviolet (P>0.05). According to our preliminary results, prostaglandin antiglaucomatous analogs do not significantly enhance pigmentation in the superficial layers of the conjunctiva. The existence of the Tyrosinase enzyme in the superficial layers of the conjunctiva suggests that basal melanocytes may transfer their melanogenic apparatus to superficial epithelial cells.

  11. Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation.

    PubMed

    Jiang, Jianxiong; Quan, Yi; Ganesh, Thota; Pouliot, Wendy A; Dudek, F Edward; Dingledine, Raymond

    2013-02-26

    Prostaglandin E2 is now widely recognized to play critical roles in brain inflammation and injury, although the responsible prostaglandin receptors have not been fully identified. We developed a potent and selective antagonist for the prostaglandin E2 receptor subtype EP2, TG6-10-1, with a sufficient pharmacokinetic profile to be used in vivo. We found that in the mouse pilocarpine model of status epilepticus (SE), systemic administration of TG6-10-1 completely recapitulates the effects of conditional ablation of cyclooxygenase-2 from principal forebrain neurons, namely reduced delayed mortality, accelerated recovery from weight loss, reduced brain inflammation, prevention of blood-brain barrier opening, and neuroprotection in the hippocampus, without modifying seizures acutely. Prolonged SE in humans causes high mortality and morbidity that are associated with brain inflammation and injury, but currently the only effective treatment is to stop the seizures quickly enough with anticonvulsants to prevent brain damage. Our results suggest that the prostaglandin receptor EP2 is critically involved in neuroinflammation and neurodegeneration, and point to EP2 receptor antagonism as an adjunctive therapeutic strategy to treat SE.

  12. Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation

    PubMed Central

    Jiang, Jianxiong; Quan, Yi; Ganesh, Thota; Pouliot, Wendy A.; Dudek, F. Edward; Dingledine, Raymond

    2013-01-01

    Prostaglandin E2 is now widely recognized to play critical roles in brain inflammation and injury, although the responsible prostaglandin receptors have not been fully identified. We developed a potent and selective antagonist for the prostaglandin E2 receptor subtype EP2, TG6-10-1, with a sufficient pharmacokinetic profile to be used in vivo. We found that in the mouse pilocarpine model of status epilepticus (SE), systemic administration of TG6-10-1 completely recapitulates the effects of conditional ablation of cyclooxygenase-2 from principal forebrain neurons, namely reduced delayed mortality, accelerated recovery from weight loss, reduced brain inflammation, prevention of blood–brain barrier opening, and neuroprotection in the hippocampus, without modifying seizures acutely. Prolonged SE in humans causes high mortality and morbidity that are associated with brain inflammation and injury, but currently the only effective treatment is to stop the seizures quickly enough with anticonvulsants to prevent brain damage. Our results suggest that the prostaglandin receptor EP2 is critically involved in neuroinflammation and neurodegeneration, and point to EP2 receptor antagonism as an adjunctive therapeutic strategy to treat SE. PMID:23401547

  13. The role of prostaglandin E2 in tumor-associated immunosuppression

    PubMed Central

    Wang, Dingzhi; DuBois, Raymond N.

    2015-01-01

    Tumor-associated inflammation can create an immunosuppressive microenvironment allowing tumor cells to escape immunosurveillance. Inhibiting immunosuppression remains one of the major challenges in cancer immunotherapy via checkpoint inhibitors. Recent preclinical data from Reis e Sousa's group may provide a strong rationale for developing new therapeutics to subvert tumor-induced immunosuppression via prostaglandin inhibition. PMID:26711015

  14. Prostaglandins modify phosphorylation of specific proteins in the insect cell line BCIRL-HzAM1

    USDA-ARS?s Scientific Manuscript database

    Prostaglandins (PGs) play crucial roles in vertebrate biology, particularly in immune functions. Because PGs also mediate specific cell functions in insect immunity, we are investigating how these signaling molecules affect insect cells. We reported that PGs, notably PGA1, PGA2, and PGE1, up and/or ...

  15. Preparation for induction of labour of the unfavourable cervix with Foley catheter compared with vaginal prostaglandin.

    PubMed

    Thomas, I L; Chenoweth, J N; Tronc, G N; Johnson, I R

    1986-02-01

    Ripening of the unfavourable cervix prior to induction of labour using traction on a Foley catheter (32 patients) was compared with 40 mg of prostaglandin F2 alpha in Tylose gel applied to the external cervical os and held in place for 12 hours with a vaginal diaphragm (25 patients). Each patient in the above groups had a modified Bishop score of 0-3 and was randomly allocated to one or other group. Comparison was made with a further 25 patients in whom the cervical score was 4-6. Timing of amniotomy and commencement of Syntocinon infusion were equivalent for all patients. Prostaglandins conferred no advantage over Foley catheter in terms of amniotomy-delivery interval, operative delivery rate, and condition of the baby one minute after birth. The disadvantages of prostaglandins for cervical ripening are a longer preparation-delivery interval, and cost ($77 versus $4.75 for the Foley catheter). Currently, prostaglandins are not officially approved for use in Australia for induction of labour. It is suggested, therefore, that the Foley catheter is preferable for ripening the unfavourable cervix as a prelude to amniotomy.

  16. Role of nitric oxide and prostaglandins in the bone formation response to mechanical loading.

    PubMed

    Chow, J W

    2000-10-01

    Nitric oxide and prostaglandins are crucial early mediators in mechanically induced bone formation. They are also responsible for the associated induction of gene expression of c-fos and IGF-1 in osteocytes, key mechanosensory cells in bone. Insight into the cellular and molecular mechanisms underlying bone formation has important implications for the maintenance of structural competence of bone.

  17. Effect of Diethylcarbamazine (DEC) on prostaglandin levels in Wuchereria bancrofti infected microfilaraemics.

    PubMed

    Sankari, T; Hoti, S L; Das, L K; Govindaraj, V; Das, P K

    2013-06-01

    Diethylcarbamazine (DEC) interferes with arachidonic acid metabolism for the clearance of microfilariae in Wuchereria bancrofti infected individuals. In this study, we have quantified the plasma concentrations of prostaglandin E2 (PGE2) and 6-keto-PGF1α, the end products of arachidonic acid metabolic pathway in microfilaraemics (DEC treated and untreated), and normal healthy individuals at pre- and 3,9,12,36, and 72 h of post-DEC treatment. We have also determined the microfilariae counts at pre and post day 2 (36 h) and day 3 (72 h) of DEC treatment by membrane filtration technique. Significant reduction in PGE2 and 6-keto-PGF1α concentrations was found at 12 h of DEC treatment. Rapid reduction in microfilarial counts was observed at 36 h of post-DEC treatment. Higher levels of prostaglandins were found at pre-treatment hours in microfilaraemics compared to normal healthy individuals (P < 0.05). Our findings indicate that DEC inhibits prostaglandins for the clearance of microfilariae, and increased levels of prostaglandins in microfilaraemics may be contributed by the parasite or host upon stimulation.

  18. Elicitability of muscle cramps in different leg and foot muscles.

    PubMed

    Minetto, Marco Alessandro; Botter, Alberto

    2009-10-01

    To explore the efficacy of muscle motor point stimulation in eliciting muscle cramps, 11 subjects underwent eight sessions of electrical stimulation of the following muscles bilaterally: abductor hallucis flexor hallucis brevis, and both heads of the gastrocnemius muscles. Bursts of 150 square wave stimuli (duration: 152 micros; current intensity: 30% supramaximal) were applied. The stimulation frequency was increased from 4 pulses per second (pps) at increments of 2 pps until a cramp was induced. The number of cramps that could be elicited was smaller in flexor hallucis brevis than in abductor hallucis (16 vs. 22 out of 22 trials each; P < 0.05) and in the lateral gastrocnemius than in the medial gastrocnemius (5 vs. 20 out of 22 trials each; P < 0.0001). We show that leg and foot muscles have different cramp susceptibility, and the intermuscle variability in the elicitability profile for electrically induced cramps supports the use of the proposed method for cramp research.

  19. Umbilical cord prostaglandins in term and preterm parturition.

    PubMed

    Hong, Joon-Seok; Romero, Roberto; Lee, Deug-Chan; Than, Nandor Gabor; Yeo, Lami; Chaemsaithong, Piya; Ahn, Soyeon; Kim, Jung-Sun; Kim, Chong Jai; Kim, Yeon Mee

    2016-01-01

    Prostaglandins (PGs) are considered the universal mediators of parturition. Amniotic fluid PGE2 and PGF2α concentrations increase before the onset of spontaneous labor at term, as well as during labor. This study was conducted to determine if the concentrations of umbilical cord PGE2 and PGF2α change with advancing gestational age, spontaneous labor at term, and preterm labor (with and without funisitis). Umbilical cord (UC) tissue samples were obtained from women (N = 158) with singleton pregnancies in the following groups: (1) term deliveries without labor (TNL; n = 20); (2) term deliveries with labor (TIL; n = 20); (3) spontaneous preterm deliveries (sPTD) with (n = 20) and without acute funisitis (n = 20); and (4) preeclampsia without labor (n = 78). The concentrations of PGs were determined in different locations of the UC. PGE2 and PGF2α were measured by specific immunoassays. Non-parametric statistics were used for analysis. (1) In spontaneous preterm deliveries, the median UC PGE2 concentration was higher in cases with funisitis than in those without funisitis (233.7 pg/µg versus 87.4 pg/µg of total protein, p = 0.001); (2) the median UC PGE2 concentration in sPTD with funisitis was also higher than that obtained from samples who had undergone labor at term (233.7 pg/µg versus 116.1 pg/µg of total protein, p = 0.03); (3) the UC PGE2 and PGF2α concentration increased as a function of advancing gestational age before 36 weeks (PGE2: ρ = 0.59, p < 0.001; PGF2α: ρ = 0.39, p = 0.01), but not after 36 weeks (PGE2: ρ = -0.1, p = 0.5; PGF2α: ρ = -0.2, p = 0.2); (4) the median UC concentrations of PGE2 and PGF2α at term was similar in samples obtained from women with and without labor (PGE2: TNL 133.7 pg/µg versus TIL 116.1 pg/µg of total protein, p = 0.9; PGF2α: TNL 8.4 pg/µg versus TIL 8.1 pg/µg of total protein, p = 0.7); and (5) there was no correlation

  20. Prostaglandin E2 after septostomy for simple transposition.

    PubMed

    Beattie, Lynne Mary; McLeod, Karen A

    2009-05-01

    In simple transposition of the great arteries (sTGA), balloon atrial septostomy is performed prior to arterial switch to improve mixing of systemic and pulmonary circulations. Following septostomy, some patients are also given prostaglandin E2 (PGE2) until surgical repair. The aims of our study were to identify how often PGE2 is given after septostomy, the indications for starting PGE2, and the effect this has on postoperative outcome. The study was a retrospective review of infants born with sTGA between 2000 and 2005, who underwent arterial switch at Yorkhill Children's Hospital, Glasgow. Over a 5-year period, 26 infants (16 male) with sTGA underwent septostomy. There was a significant rise in mean oxygen saturation following septostomy (mean, 61.4 +/- 11.5% before, 81.5 +/- 9.4% after; p < 0.05). Four of 26 (15%) did not receive PGE2 at all (group 1) and 8 of 26 (30%) received PGE2 before but not after septostomy (group 2). A total of 14 of 26 infants (54%) were given PGE2 following septostomy. This comprised 11 who received PGE2 before and after septostomy (group 3) and 3 who did not receive PGE2 prior to septostomy but did after (group 4). Groups 2 and 3 were compared directly, as they both received PGE2 before septostomy. In group 3, oxygen saturations were lower when PGE2 was started compared with saturations immediately after septostomy (45 +/- 23.6% vs. 80 +/- 10.3%; p < 0.05). Groups 2 and 3 showed no difference in atrial gap after septostomy (9.4 +/- 3 vs. 8 +/- 1 mm; p > 0.05). Fifty percent of infants in group 3 underwent echocardiography prior to restarting PGE2, which revealed a patent arterial duct in all but one patient. Despite PGE2, Group 3 had lower saturations at arterial switch compared with Group 2 (71 +/- 14% vs. 82 +/- 8%; p < 0.05). No difference was observed between group 2 and group 3 with regard to length of cardiopulmonary bypass (group 2, 173 +/- 101.4 min, vs. group 3, 157.9 +/- 42.1 min; p > 0.05). However, the Intensive Care Unit

  1. Biologically inspired robots elicit a robust fear response in zebrafish

    NASA Astrophysics Data System (ADS)

    Ladu, Fabrizio; Bartolini, Tiziana; Panitz, Sarah G.; Butail, Sachit; Macrı, Simone; Porfiri, Maurizio

    2015-03-01

    We investigate the behavioral response of zebrafish to three fear-evoking stimuli. In a binary choice test, zebrafish are exposed to a live allopatric predator, a biologically-inspired robot, and a computer-animated image of the live predator. A target tracking algorithm is developed to score zebrafish behavior. Unlike computer-animated images, the robotic and live predator elicit a robust avoidance response. Importantly, the robotic stimulus elicits more consistent inter-individual responses than the live predator. Results from this effort are expected to aid in hypothesis-driven studies on zebrafish fear response, by offering a valuable approach to maximize data-throughput and minimize animal subjects.

  2. Towards Effective Elicitation of NIN-AND Tree Causal Models

    NASA Astrophysics Data System (ADS)

    Xiang, Yang; Li, Yu; Zhu, Zoe Jingyu

    To specify a Bayes net (BN), a conditional probability table (CPT), often of an effect conditioned on its n causes, needs assessed for each node. It generally has the complexity exponential on n. Noisy-OR reduces the complexity to linear, but can only represent reinforcing causal interactions. The non-impeding noisy-AND (NIN-AND) tree is the first causal model that explicitly expresses reinforcement, undermining, and their mixture. It has linear complexity, but requires elicitation of a tree topology for types of causal interactions. We study their topology space and develop two novel techniques for more effective elicitation.

  3. Anti-inflammatory R-prostaglandins from Caribbean Colombian soft coral Plexaura homomalla.

    PubMed

    Reina, Eduardo; Ramos, Freddy A; Castellanos, Leonardo; Aragón, Marcela; Ospina, Luis F

    2013-11-01

    This study aims to evaluate the effect of prostaglandins isolated from soft coral Plexaura homomalla, collected in Colombian Caribbean Sea, on in vivo and in vitro inflammation models. Extracts from P. homomalla were fractionated and sequentially chromatographed to obtain the prostaglandins: (15R)-PGA2 (1), (15R)-PGA2 -Me (2), (15R)-O-Ac-PGA2 (3), (15R)-O-Ac-PGA2 -Me (4) and (15R)-PGE2 (5) in addition to three semi-synthetic prostaglandins obtained by transformations of the natural products. The anti-inflammatory properties of natural and semi-synthetic compounds were determined in vivo using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear oedema model and in vitro leucocyte degranulation, myeloperoxidase (MPO) and elastase enzymatic activities from human polymorphonuclear cells (PMNs). The cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In the in vivo assay, (15R)-PGE2 (1) and (15R)-O-Ac-PGA2 (3) showed anti-inflammatory activity, as well as in vitro inhibition of elastase release from PMNs. In the PMNs degranulation assay, (15R)-PGE2 (5), was the most active compound in the inhibition of MPO release. Finally, all the tested prostaglandins showed moderate inhibition for elastase enzyme activity, whereas none of the prostaglandins exhibit significative inhibition on MPO activity. (15R)-PGE2 (1) and (15R)-O-Ac-PGA2 (3) present significant inhibition on three important events related to the topical inflammatory response induced by TPA: the oedema formation, the PMNs degranulation, events that modulate MPO and elastase levels at inflammation site, and the inhibition of the enzyme activity. © 2013 Royal Pharmaceutical Society.

  4. Inhibition of the Prostaglandin Transporter PGT Lowers Blood Pressure in Hypertensive Rats and Mice

    PubMed Central

    Chi, Yuling; Jasmin, Jean-Francois; Seki, Yoshinori; Lisanti, Michael P.; Charron, Maureen J.; Lefer, David J.; Schuster, Victor L.

    2015-01-01

    Inhibiting the synthesis of endogenous prostaglandins with nonsteroidal anti-inflammatory drugs exacerbates arterial hypertension. We hypothesized that the converse, i.e., raising the level of endogenous prostaglandins, might have anti-hypertensive effects. To accomplish this, we focused on inhibiting the prostaglandin transporter PGT (SLCO2A1), which is the obligatory first step in the inactivation of several common PGs. We first examined the role of PGT in controlling arterial blood pressure blood pressure using anesthetized rats. The high-affinity PGT inhibitor T26A sensitized the ability of exogenous PGE2 to lower blood pressure, confirming both inhibition of PGT by T26A and the vasodepressor action of PGE2 T26A administered alone to anesthetized rats dose-dependently lowered blood pressure, and did so to a greater degree in spontaneously hypertensive rats than in Wistar-Kyoto control rats. In mice, T26A added chronically to the drinking water increased the urinary excretion and plasma concentration of PGE2 over several days, confirming that T26A is orally active in antagonizing PGT. T26A given orally to hypertensive mice normalized blood pressure. T26A increased urinary sodium excretion in mice and, when added to the medium bathing isolated mouse aortas, T26A increased the net release of PGE2 induced by arachidonic acid, inhibited serotonin-induced vasoconstriction, and potentiated vasodilation induced by exogenous PGE2. We conclude that pharmacologically inhibiting PGT-mediated prostaglandin metabolism lowers blood pressure, probably by prostaglandin-induced natriuresis and vasodilation. PGT is a novel therapeutic target for treating hypertension. PMID:26121580

  5. Expression of microsomal prostaglandin e synthase-1 in fibroblasts of rabbit alkali-burned corneas.

    PubMed

    Kawamura, Aruha; Tatsuguchi, Atsushi; Ishizaki, Masamichi; Takahashi, Hiroshi; Fukuda, Yuh

    2008-12-01

    Prostaglandin E2 is related to wound healing. Three different prostaglandin E synthases have been identified: microsomal prostaglandin E synthase (mPGES)-1, mPGES-2, and cytosolic prostaglandin E synthase. This study examined mPGES-1 expression in the cornea during the reparative process that occurs after an alkali burn. mPGES-1 messenger RNA (mRNA) and protein expression levels were examined by reverse transcription-polymerase chain reaction and Western blot analysis. Localization of mPGES-1 mRNA was examined by in situ hybridization. Using immunostaining, the localization of mPGES-1, cyclooxygenase (COX)-2, and alpha-smooth muscle actin (alpha-SMA) protein was studied. Although mPGES-1 mRNA is expressed in normal cornea, after a corneal injury, a progressive increase of mPGES-1 mRNA occurs. In this study, 2-6 weeks after injury, mPGES-1 mRNA was detected in the stromal spindle cells. Western blot analysis also showed that mPGES-1 protein expression was observed in normal cornea, with an increase noted from 2 to 4 weeks after corneal injury. mPGES-1 immunoreactivity was negative in normal cornea; however, starting at 2 weeks after injury, positive staining of the stromal spindle cells was noted. Although COX-2 and alpha-SMA immunoreactivities were negative in the stroma of normal cornea, after injury, staining was observed in the stromal spindle cells. alpha-SMA-positive cells and myofibroblasts express mPGES-1 mRNA and protein, and in addition, mPGES-1 colocalized with COX-2, suggesting that myofibroblasts synthesize prostaglandin E2 and may act on and accelerate corneal wound healing.

  6. Inhibitors of phosphodiesterases PDE2, PDE3, and PDE4 do not increase the sinoatrial tachycardia of noradrenaline and prostaglandin PGE₁ in mice.

    PubMed

    Galindo-Tovar, Alejandro; Vargas, María Luisa; Kaumann, Alberto J

    2016-02-01

    Phosphodiesterases PDE2, PDE3, and PDE4 are expressed in murine sinoatrial cells. PDE3 and/or PDE4 reduce heart rate but apparently do not influence the tachycardia mediated through sinoatrial β1- and β2-adrenoceptors despite the high content of sinoatrial cAMP. The function of PDE2 is, however, uncertain. Prostaglandin PGE1 elicits sinoatrial tachycardia through EP receptors, but the control by phosphodiesterases is unknown. We investigated on spontaneously beating right atria of mice the effects of the PDE2 inhibitors Bay 60-7550 and EHNA on basal beating and the tachycardia produced by noradrenaline (3 nM) and PGE1 (1 μM). Bay 60-7550 (1 μM), but not EHNA (10 μM), increased basal sinoatrial beating. EHNA also failed to produce tachycardia in the presence of the adenosine deaminase inhibitor 2'-deoxycoformycin (10 μM), remaining inconclusive whether PDE2 reduces basal sinoatrial beating. Rolipram (10 μM) and cilostamide (300 nM) caused moderate tachycardia. The tachycardia evoked by Bay 60-7550 was similar in the absence and presence of rolipram. Noradrenaline elicited stable tachycardia that was not increased by Bay 60-7550. A stable tachycardia caused by PGE1 was not increased by the inhibitors of PDE2, PDE3, and PDE4. Unlike PDE3 and PDE4 which reduce murine basal sinoatrial beating, a possible effect of PDE2 needs further research. The stable tachycardia produced by noradrenaline and PGE1, together with the lack potentiation by the inhibitors of PDE2, PDE3, and PDE4, suggests that cAMP generated at the receptor compartments is hardly hydrolyzed by these phophodiesterases. Evidence from human volunteers is consistent with this proposal.

  7. Elicitation Support Requirements of Multi-Expertise Teams

    ERIC Educational Resources Information Center

    Bitter-Rijpkema, Marlies; Martens, Rob; Jochems, Wim

    2005-01-01

    Tools to support knowledge elicitation are used more and more in situations where employees or students collaborate using the computer. Studies indicate that differences exist between experts and novices regarding their methods of work and reasoning. However, the commonly preferred approach tends to deal with team members as a single system with…

  8. Elicited Production of Relative Clauses in Children with Williams Syndrome

    ERIC Educational Resources Information Center

    Zukowski, Andrea

    2009-01-01

    Relative clauses have been implicated alternately as a strength and a weakness in the language of people with Williams Syndrome (WS). To clarify the facts, an elicited production test was administered to 10 people with WS (age 10-16 years), 10 typically developing children (age 4-7 years), and 12 typically developing adults. Nearly every WS…

  9. NEURAL RESPONSES ELICITED BY ELECTRICAL STIMULATION OF THE RETINA

    PubMed Central

    Chen, Shih-Jen; Mahadevappa, Manjunatha; Roizenblatt, Roberto; Weiland, James; Humayun, Mark

    2006-01-01

    Purpose To study electrically elicited responses (EERs) that are produced by epiretinal stimulation of normal and degenerated retina. Methods Three biological models of retinal degeneration are compared: normal and rd1 mouse, normal and RCD1 dog, and human with retinitis pigmentosa. In mouse, epiretinal stimulation was accomplished by means of a wire inserted in the vitreous cavity, and single-unit activity was recorded in visual cortex. In dog and human, an implantable retinal stimulator was used to stimulate the retina, and evoked potentials were recorded from the cortical surface (dog) or scalp (human). Results Analysis of EERs revealed distinct early (less than 10 ms) and late (greater than 50 ms) responses. Synaptic blockers abolished the late response but not the early response. For eliciting the early response in normal and rd mice, a square pulse stimulus was more efficient than the sine wave or pulse train. In normal and degenerate canine retina, electrically elicited responses also exhibited early and late phases. EERs in a retinal prosthesis test subject (with retinitis pigmentosa) showed latency similar to the canine, but no evidence of an early response, possibly due to the lack of sensitivity in scalp (human) vs cortical surface (canine) electrode placement. Conclusion EERs could be elicited from both normal and degenerated retina. Mouse, dog, and human EERs showed common characteristics. PMID:17471346

  10. Creating a Framework: Art Therapy Elicits the Narrative

    ERIC Educational Resources Information Center

    Harber, Karen

    2011-01-01

    A case study illustrates how art therapy was used to elicit the narrative of an adolescent male student in transition from incarceration to a transfer school setting. Childhood trauma was addressed in individual sessions and within a literacy group co-led by a reading specialist. The art therapist responded to the client's needs by broadening the…

  11. Creating a Framework: Art Therapy Elicits the Narrative

    ERIC Educational Resources Information Center

    Harber, Karen

    2011-01-01

    A case study illustrates how art therapy was used to elicit the narrative of an adolescent male student in transition from incarceration to a transfer school setting. Childhood trauma was addressed in individual sessions and within a literacy group co-led by a reading specialist. The art therapist responded to the client's needs by broadening the…

  12. Clinicians as Communication Partners: Developing a Mediated Discourse Elicitation Protocol

    ERIC Educational Resources Information Center

    Hengst, Julie A.; Duff, Melissa C.

    2007-01-01

    This article presents the development and piloting of a mediated discourse elicitation protocol. Grounded in situated theories of communication and informed by mediated discourse analysis, this protocol selectively samples familiar discourse types in a manner designed to preserve interactional aspects of communication. Critically, the mediated…

  13. Eliciting Design Patterns for E-Learning Systems

    ERIC Educational Resources Information Center

    Retalis, Symeon; Georgiakakis, Petros; Dimitriadis, Yannis

    2006-01-01

    Design pattern creation, especially in the e-learning domain, is a highly complex process that has not been sufficiently studied and formalized. In this paper, we propose a systematic pattern development cycle, whose most important aspects focus on reverse engineering of existing systems in order to elicit features that are cross-validated through…

  14. Using Automatic Speech Recognition Technology with Elicited Oral Response Testing

    ERIC Educational Resources Information Center

    Cox, Troy L.; Davies, Randall S.

    2012-01-01

    This study examined the use of automatic speech recognition (ASR) scored elicited oral response (EOR) tests to assess the speaking ability of English language learners. It also examined the relationship between ASR-scored EOR and other language proficiency measures and the ability of the ASR to rate speakers without bias to gender or native…

  15. The Role of Elicited Verbal Imitation in Toddlers' Word Learning

    ERIC Educational Resources Information Center

    Hodges, Rosemary; Munro, Natalie; Baker, Elise; McGregor, Karla; Docking, Kimberley; Arciuli, Joanne

    2016-01-01

    This study is about the role of elicited verbal imitation in toddler word learning. Forty-eight toddlers were taught eight nonwords linked to referents. During training, they were asked to imitate the nonwords. Naming of the referents was tested at three intervals (one minute later [uncued], five minutes, and 1-7 days later [cued]) and recognition…

  16. Using Automatic Speech Recognition Technology with Elicited Oral Response Testing

    ERIC Educational Resources Information Center

    Cox, Troy L.; Davies, Randall S.

    2012-01-01

    This study examined the use of automatic speech recognition (ASR) scored elicited oral response (EOR) tests to assess the speaking ability of English language learners. It also examined the relationship between ASR-scored EOR and other language proficiency measures and the ability of the ASR to rate speakers without bias to gender or native…

  17. Preparing Beginning Teachers to Elicit and Interpret Students' Mathematical Thinking

    ERIC Educational Resources Information Center

    Sleep, Laurie; Boerst, Timothy A.

    2012-01-01

    This study investigated how teacher education assignments can be designed to support beginning teachers in learning to do the work of teaching. We examined beginners' formative assessment practices--in particular, their eliciting and interpreting of students' mathematical thinking--in the context of an elementary mathematics methods assignment,…

  18. Modification of commercially available simulators to elicit decision making behavior.

    PubMed

    Salud, Jonathan; Ononye, Chiagozie; Salud, Lawrence; Pugh, Carla

    2012-01-01

    In recent years, simulation training has emerged as an innovative method for decreasing error and teaching complex procedures. Simulation has also been a valuable tool for evaluating investigatory and analytic thinking. By adding a specific, clinically oriented modification to a commercially available simulator, we were able to elicit first-year emergency medicine resident perceptions, actions, and decisions.

  19. A Study of the Affective Responses Elicited by Occupational Stimuli

    ERIC Educational Resources Information Center

    Schoon, Craig G.

    1976-01-01

    The semantic differential was used to assess the properties of affect elicited by occupational stimuli. Vocationally committed men studying medicine, business, and engineering responded to a semantic differential containing occupational concepts. Results show a semantic space for all three groups composed of three orthogonal dimensions of affect…

  20. Transfer of Aversive Respondent Elicitation in Accordance with Equivalence Relations

    ERIC Educational Resources Information Center

    Valverde, Miguel Rodriguez; Luciano, Carmen; Barnes-Holmes, Dermot

    2009-01-01

    The present study investigates the transfer of aversively conditioned respondent elicitation through equivalence classes, using skin conductance as the measure of conditioning. The first experiment is an attempt to replicate Experiment 1 in Dougher, Augustson, Markham, Greenway, and Wulfert (1994), with different temporal parameters in the…

  1. Eliciting Production of L2 Target Structures through Priming Activities

    ERIC Educational Resources Information Center

    McDonough, Kim; Trofimovich, Pavel; Neumann, Heike

    2015-01-01

    This study focuses on the pedagogical applications of structural priming research in an English for academic purposes (EAP) context, investigating whether priming activities are an effective tool for eliciting production of target grammatical structures. University students across four EAP classes carried out a total of 6 information-exchange…

  2. Visual emotional context modulates brain potentials elicited by unattended tones.

    PubMed

    Sugimoto, Sayaka; Nittono, Hiroshi; Hori, Tadao

    2007-10-01

    To examine whether brain electrical responses to environmental stimuli were influenced by emotional contexts, event-related potentials (ERPs) elicited by nonstartle probe tones were recorded from 13 student volunteers while they were viewing emotionally positive, neutral, and negative slides of the International Affective Picture System. The auditory stimuli consisted of high-deviant (2000 Hz, p=.08), low-deviant (1050 Hz, p=.08), and standard (1000 Hz, p=.84) tones with a mean onset-to-onset interval of 600 ms. Participants were told to ignore the tones. High-deviant tones elicited a larger N1 (peaking around 100 ms) when participants were viewing negative slides than when viewing positive slides. The amplitude of the P2 elicited by standard tones (peaking around 170 ms) was smaller when participants were viewing positive slides than when viewing negative and neutral slides. The amplitude of the mismatch negativity (150-200 ms) tended to reduce during positive slide presentation, but this difference appeared to be due to reduction of the P2 elicited by standard tones. These findings suggest that visually induced emotional states have a sequential effect on auditory information processing, in that the influence of negative emotion appears at an earlier stage than that of positive emotion.

  3. Bacterial elicitation and evasion of plant innate immunity

    PubMed Central

    Abramovitch, Robert B.; Anderson, Jeffrey C.; Martin, Gregory B.

    2010-01-01

    Recent research on plant responses to bacterial attack has identified extracellular and intracellular host receptors that recognize conserved pathogen-associated molecular patterns and more specialized virulence proteins, respectively. These findings have shed light on our understanding of the molecular mechanisms by which bacteria elicit host defences and how pathogens have evolved to evade or suppress these defences. PMID:16936700

  4. Elicited Production of Relative Clauses in Children with Williams Syndrome

    ERIC Educational Resources Information Center

    Zukowski, Andrea

    2009-01-01

    Relative clauses have been implicated alternately as a strength and a weakness in the language of people with Williams Syndrome (WS). To clarify the facts, an elicited production test was administered to 10 people with WS (age 10-16 years), 10 typically developing children (age 4-7 years), and 12 typically developing adults. Nearly every WS…

  5. Intermediary's Information Seeking, Inquiring Minds, and Elicitation Styles.

    ERIC Educational Resources Information Center

    Wu, Mei-Mei; Liu, Ying-Hsang

    2003-01-01

    Explores how intermediaries seek information from patrons by analyzing intermediaries' elicitation utterances through three dimensions: linguistic forms, utterance purposes, and communicative functions. Reports on results of questionnaires given to patrons and intermediaries in academic and research libraries in Taiwan and investigates…

  6. Web-Based Elicitation Tasks in SLA Research.

    ERIC Educational Resources Information Center

    Ayoun, Dalila

    2000-01-01

    Studied second language acquisition (SLA) designed with Web-based elicitation tasks to obtain greater internal and external validity. Tested the acquisition of the properties subsumed under the verb movement parameter and the null subject parameter by English native speakers enrolled in college French. (Author/VWL)

  7. A Task that Elicits Reasoning: A Dual Analysis

    ERIC Educational Resources Information Center

    Yankelewitz, Dina; Mueller, Mary; Maher, Carolyn A.

    2010-01-01

    This paper reports on the forms of reasoning elicited as fourth grade students in a suburban district and sixth grade students in an urban district worked on similar tasks involving reasoning with the use of Cuisenaire rods. Analysis of the two data sets shows similarities in the reasoning used by both groups of students on specific tasks, and the…

  8. Photo-Elicitation Method Gives Voice and Reactions of Subjects.

    ERIC Educational Resources Information Center

    Smith, C. Zoe; Woodward, Anne-Marie

    1999-01-01

    Describes a research assignment (called "photo-elicitation") in a graduate course on the role of photography in society in which students interview people similar to the subjects in the photographs to discover how the photographs affect them. Includes material from one research project interviewing three recovering drug addicts responding to Larry…

  9. Transfer of Aversive Respondent Elicitation in Accordance with Equivalence Relations

    ERIC Educational Resources Information Center

    Valverde, Miguel Rodriguez; Luciano, Carmen; Barnes-Holmes, Dermot

    2009-01-01

    The present study investigates the transfer of aversively conditioned respondent elicitation through equivalence classes, using skin conductance as the measure of conditioning. The first experiment is an attempt to replicate Experiment 1 in Dougher, Augustson, Markham, Greenway, and Wulfert (1994), with different temporal parameters in the…

  10. A Study of the Affective Responses Elicited by Occupational Stimuli

    ERIC Educational Resources Information Center

    Schoon, Craig G.

    1976-01-01

    The semantic differential was used to assess the properties of affect elicited by occupational stimuli. Vocationally committed men studying medicine, business, and engineering responded to a semantic differential containing occupational concepts. Results show a semantic space for all three groups composed of three orthogonal dimensions of affect…

  11. Engaging Young Children in Research through Photo Elicitation

    ERIC Educational Resources Information Center

    Pyle, Angela

    2013-01-01

    Embracing the new sociology of childhood, this paper describes a participatory research method built on a belief in the competency of young children. The paper begins with a critical review of the photo elicitation literature exploring the varied levels of children's participation. Drawing on the strengths of the previous research, a multi-step…

  12. Pattern Visual Evoked Potentials Elicited by Organic Electroluminescence Screen

    PubMed Central

    Matsumoto, Celso Soiti; Shinoda, Kei; Matsumoto, Harue; Funada, Hideaki; Minoda, Haruka

    2014-01-01

    Purpose. To determine whether organic electroluminescence (OLED) screens can be used as visual stimulators to elicit pattern-reversal visual evoked potentials (p-VEPs). Method. Checkerboard patterns were generated on a conventional cathode-ray tube (S710, Compaq Computer Co., USA) screen and on an OLED (17 inches, 320 × 230 mm, PVM-1741, Sony, Tokyo, Japan) screen. The time course of the luminance changes of each monitor was measured with a photodiode. The p-VEPs elicited by these two screens were recorded from 15 eyes of 9 healthy volunteers (22.0 ± 0.8 years). Results. The OLED screen had a constant time delay from the onset of the trigger signal to the start of the luminescence change. The delay during the reversal phase from black to white for the pattern was 1.0 msec on the cathode-ray tube (CRT) screen and 0.5 msec on the OLED screen. No significant differences in the amplitudes of P100 and the implicit times of N75 and P100 were observed in the p-VEPs elicited by the CRT and the OLED screens. Conclusion. The OLED screen can be used as a visual stimulator to elicit p-VEPs; however the time delay and the specific properties in the luminance change must be taken into account. PMID:25197652

  13. Pattern visual evoked potentials elicited by organic electroluminescence screen.

    PubMed

    Matsumoto, Celso Soiti; Shinoda, Kei; Matsumoto, Harue; Funada, Hideaki; Sasaki, Kakeru; Minoda, Haruka; Iwata, Takeshi; Mizota, Atsushi

    2014-01-01

    To determine whether organic electroluminescence (OLED) screens can be used as visual stimulators to elicit pattern-reversal visual evoked potentials (p-VEPs). Checkerboard patterns were generated on a conventional cathode-ray tube (S710, Compaq Computer Co., USA) screen and on an OLED (17 inches, 320 × 230 mm, PVM-1741, Sony, Tokyo, Japan) screen. The time course of the luminance changes of each monitor was measured with a photodiode. The p-VEPs elicited by these two screens were recorded from 15 eyes of 9 healthy volunteers (22.0 ± 0.8 years). The OLED screen had a constant time delay from the onset of the trigger signal to the start of the luminescence change. The delay during the reversal phase from black to white for the pattern was 1.0 msec on the cathode-ray tube (CRT) screen and 0.5 msec on the OLED screen. No significant differences in the amplitudes of P100 and the implicit times of N75 and P100 were observed in the p-VEPs elicited by the CRT and the OLED screens. The OLED screen can be used as a visual stimulator to elicit p-VEPs; however the time delay and the specific properties in the luminance change must be taken into account.

  14. The Role of Elicited Verbal Imitation in Toddlers' Word Learning

    ERIC Educational Resources Information Center

    Hodges, Rosemary; Munro, Natalie; Baker, Elise; McGregor, Karla; Docking, Kimberley; Arciuli, Joanne

    2016-01-01

    This study is about the role of elicited verbal imitation in toddler word learning. Forty-eight toddlers were taught eight nonwords linked to referents. During training, they were asked to imitate the nonwords. Naming of the referents was tested at three intervals (one minute later [uncued], five minutes, and 1-7 days later [cued]) and recognition…

  15. Eliciting Production of L2 Target Structures through Priming Activities

    ERIC Educational Resources Information Center

    McDonough, Kim; Trofimovich, Pavel; Neumann, Heike

    2015-01-01

    This study focuses on the pedagogical applications of structural priming research in an English for academic purposes (EAP) context, investigating whether priming activities are an effective tool for eliciting production of target grammatical structures. University students across four EAP classes carried out a total of 6 information-exchange…

  16. Eliciting Students' Beliefs about Who Is Good at Mathematics

    ERIC Educational Resources Information Center

    Morge, Shelby P.

    2007-01-01

    This article highlights a series of activities designed to elicit students' mathematics-related beliefs, particularly those related to gender. As a result of the activities, females in upper-level classes rated themselves as having less confidence than males, and viewing a movie clip was sufficient for some students to modify their descriptions of…

  17. Photo-Elicitation Method Gives Voice and Reactions of Subjects.

    ERIC Educational Resources Information Center

    Smith, C. Zoe; Woodward, Anne-Marie

    1999-01-01

    Describes a research assignment (called "photo-elicitation") in a graduate course on the role of photography in society in which students interview people similar to the subjects in the photographs to discover how the photographs affect them. Includes material from one research project interviewing three recovering drug addicts responding to Larry…

  18. Elicitation Support Requirements of Multi-Expertise Teams

    ERIC Educational Resources Information Center

    Bitter-Rijpkema, Marlies; Martens, Rob; Jochems, Wim

    2005-01-01

    Tools to support knowledge elicitation are used more and more in situations where employees or students collaborate using the computer. Studies indicate that differences exist between experts and novices regarding their methods of work and reasoning. However, the commonly preferred approach tends to deal with team members as a single system with…

  19. Photo-Elicitation: Reflexivity on Method, Analysis, and Graphic Portraits

    ERIC Educational Resources Information Center

    Richard, Veronica M.; Lahman, Maria K. E.

    2015-01-01

    In this methodological discussion, the authors detail and reflect on the processes of using photo-elicitation interviewing as a way to align with positive qualitative methodologies, to gain access to participant beliefs and values, and to highlight participant voices through their choices of words and visuals. A review of the literature and an…

  20. Engaging Young Children in Research through Photo Elicitation

    ERIC Educational Resources Information Center

    Pyle, Angela

    2013-01-01

    Embracing the new sociology of childhood, this paper describes a participatory research method built on a belief in the competency of young children. The paper begins with a critical review of the photo elicitation literature exploring the varied levels of children's participation. Drawing on the strengths of the previous research, a multi-step…

  1. Eliciting Students' Beliefs about Who Is Good at Mathematics

    ERIC Educational Resources Information Center

    Morge, Shelby P.

    2007-01-01

    This article highlights a series of activities designed to elicit students' mathematics-related beliefs, particularly those related to gender. As a result of the activities, females in upper-level classes rated themselves as having less confidence than males, and viewing a movie clip was sufficient for some students to modify their descriptions of…

  2. Computational Support for Early Elicitation and Classification of Tone

    ERIC Educational Resources Information Center

    Bird, Steven; Lee, Haejoong

    2014-01-01

    Investigating a tone language involves careful transcription of tone on words and phrases. This is challenging when the phonological categories--the tones or melodies--have not been identified. Effects such as coarticulation, sandhi, and phrase-level prosody appear as obstacles to early elicitation and classification of tone. This article presents…

  3. Eliciting Student Views Using an Interview-About-Instances Technique.

    ERIC Educational Resources Information Center

    Gilbert, John K.; And Others

    An exposition is made of a method to elicit students' comprehension of the meaning of words commonly used in science, which may be influential in determining what they learn. The method's aim is to elucidate features in students' understanding of childrens' science (that found before formal teaching of science), student science (that found after…

  4. A Task that Elicits Reasoning: A Dual Analysis

    ERIC Educational Resources Information Center

    Yankelewitz, Dina; Mueller, Mary; Maher, Carolyn A.

    2010-01-01

    This paper reports on the forms of reasoning elicited as fourth grade students in a suburban district and sixth grade students in an urban district worked on similar tasks involving reasoning with the use of Cuisenaire rods. Analysis of the two data sets shows similarities in the reasoning used by both groups of students on specific tasks, and the…

  5. Computational Support for Early Elicitation and Classification of Tone

    ERIC Educational Resources Information Center

    Bird, Steven; Lee, Haejoong

    2014-01-01

    Investigating a tone language involves careful transcription of tone on words and phrases. This is challenging when the phonological categories--the tones or melodies--have not been identified. Effects such as coarticulation, sandhi, and phrase-level prosody appear as obstacles to early elicitation and classification of tone. This article presents…

  6. 15-Deoxy-{delta}{sup 12,14}-prostaglandin J{sub 2}-induced down-regulation of endothelial nitric oxide synthase in association with HSP70 induction

    SciTech Connect

    Hwang, Jinah; Lee, Hyun-Il; Chang, Young-Sun; Lee, Soo Jae; Kim, Kwang Pyo; Park, Sang Ick . E-mail: parksi@nih.go.kr

    2007-05-25

    A natural ligand of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), 15-deoxy-{delta}{sup 12,14}-prostaglandin J{sub 2} (15d-PGJ{sub 2}), decreases endothelial nitric oxide synthase (eNOS) expression by an unknown mechanism. Here we found that 15d-PGJ{sub 2}-induced eNOS reduction is inversely associated with heat shock protein 70 (HSP70) induction in endothelial cells. Treatment of cells with 15d-PGJ{sub 2} decreased eNOS protein expression in a concentration- and time-dependent manner, but independently of PPAR{gamma} with no effect on mRNA levels. Although 15d-PGJ{sub 2} elicited endothelial apoptosis, inhibition of both pan-caspases and cathepsins failed to reverse reduction of eNOS protein. Interestingly, we observed that 15d-PGJ{sub 2} induced HSP70 in a dose-dependent manner. Immunoprecipitation and heat shock treatment demonstrated that eNOS reduction was strongly related to HSP70 induction. Cellular fractionation revealed that treatment with 15d-PGJ{sub 2} increased eNOS distribution 2.5-fold from soluble to insoluble fractions. These findings provide new insights into mechanisms whereby eNOS regulation by 15d-PGJ{sub 2} is related to HSP70 induction.

  7. Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term.

    PubMed

    Kelly, Anthony J; Malik, Sidra; Smith, Lee; Kavanagh, Josephine; Thomas, Jane

    2009-10-07

    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. 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). We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2009) and bibliographies of relevant papers. 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. We assessed studies and extracted data independently. 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

  8. Different effects of growth hormone-releasing hormone (GRH) and somatostatin on growth hormone and stable metabolite of prostaglandin E2, 13, 14-dihydro-15-keto-prostaglandin E2 (PGE2-M) in normal subjects.

    PubMed

    Zacharieva, S; Muchá, I; Popova, J; Andonova, K

    1992-01-01

    Twenty four healthy subjects were placed in two treatment groups: 1. The first group consisted of twelve subjects in whom growth releasing hormone (GRH) (1 microgram/kg.BW) resulted in a marked and sustained elevation of serum growth hormone (GH) and a slight and delayed increase in plasma prostaglandin E2-M. In the second group, consisting also of twelve subjects, somatostatin infusion (500 micrograms/250 ml) was initiated and maintained for 60 min. Serum GH significantly decreased at 30 and 60 min during infusion and 15 min thereafter. We did not observe any changes in plasma prostaglandin E2-M during or after somatostatin infusion. The results obtained confirm previous in vitro studies and suggest a possible link between growth releasing hormone and prostaglandin E2 in their action on growth hormone secretion. It seems that somatostatin does not play a role in the control of prostaglandin E2 release.

  9. 15-deoxy prostaglandin J2, the nonenzymatic metabolite of prostaglandin D2, induces apoptosis in keratinocytes of human hair follicles: a possible explanation for prostaglandin D2-mediated inhibition of hair growth.

    PubMed

    Joo, Hyun Woo; Kang, Yoo Ri; Kwack, Mi Hee; Sung, Young Kwan

    2016-07-01

    Recent studies have shown that prostaglandin D2 (PGD2) and its nonenzymatic metabolite, 15-deoxy-Δ(12,14)-prostaglandin J2 (15-dPGJ2), inhibit in vitro growth of explanted human hair follicles and inhibit hair growth in mice through the GPR44 (DP2). However, the underlying mechanism is still unclear. In this study, we first investigated the expression of DP2 in human hair follicles and in cultured follicular cells. We found that DP2 is strongly expressed in the outer root sheath (ORS) cells and weakly expressed in the dermal papilla (DP) cells. We observed slight growth stimulation when ORS and DP cells were treated with PGD2. We also observed slight growth stimulation when DP and ORS cells were treated with low concentrations (0.5 and 1 μM) of 15-dPGJ2. However, 5 μM 15-dPGJ2 inhibited the viability and caused apoptosis of both cell types. Exposure of cultured human hair follicles to 15-dPGJ2 resulted in significant apoptosis in follicular keratinocytes. Altogether, our data provide an evidence that 15-dPGJ2 promotes apoptosis in follicular keratinocytes and provide rationale for developing remedies for the prevention and treatment of hair loss based on DP2 antagonism.

  10. Tryptophan-2,3-dioxygenase is regulated by prostaglandin E2 in malignant glioma via a positive signaling loop involving prostaglandin E receptor-4.

    PubMed

    Ochs, Katharina; Ott, Martina; Rauschenbach, Katharina J; Deumelandt, Katrin; Sahm, Felix; Opitz, Christiane A; von Deimling, Andreas; Wick, Wolfgang; Platten, Michael

    2015-12-27

    Malignant gliomas and other types of tumors generate a local immunosuppressive microenvironment, which prohibits an effective anti-tumor immune response and promotes tumor growth. Along with others, we have recently demonstrated that catabolism of the essential amino acid tryptophan via tryptophan-2,3-dioxygenase (TDO) is an important mechanism mediating tumor-associated immunosuppression particularly in gliomas. The pathways regulating TDO in tumors, however, are poorly understood. Here we show that prostaglandins enhance TDO expression and enzymatic activity in malignant gliomas via activation of prostaglandin E receptor-4 (EP4). Stimulation with prostaglandin E2 (PGE2 ) up-regulated TDO-mediated kynurenine release in human glioma cell lines while knockdown of the PGE2 receptor EP4 inhibited TDO expression and activity. In human malignant glioma tissue expression of the PGE2 -producing enzyme cyclooxygenase-2 (COX2) and its receptor EP4 were associated with TDO expression both on transcript and protein level. High expression of EP4 correlated with poor survival in malignant glioma patients WHO III-IV. Importantly, treatment of glioma cells with an EP4 inhibitor decreased TDO expression and activity. Moreover, TDO-over-expressing murine gliomas showed increased COX2 and EP4 expression suggesting a positive feedback mechanism in vivo. In summary, targeting EP4 may inhibit - in addition to immunosuppressive COX2 signaling - tryptophan degradation as another important immunosuppressive pathway and thus, could provide a dual clinically relevant immunotherapeutic avenue for the treatment of malignant gliomas. This article is protected by copyright. All rights reserved.

  11. TGF-beta 1 inhibits both endotoxin-induced prostaglandin synthesis and expression of the TIS10/prostaglandin synthase 2 gene in murine macrophages.

    PubMed

    Reddy, S T; Gilbert, R S; Xie, W; Luner, S; Herschman, H R

    1994-02-01

    Activated macrophages produce substantial quantities of paracrine mediators, including cytokines, nitric oxide, and prostaglandins. Transforming growth factor beta 1 (TGF-beta) is a potent modulator of immune function. TGF-beta inhibits the cytotoxic activity of endotoxin/lipopolysaccharide (LPS)-activated macrophage cell lines and primary macrophage cultures, reducing their expression of cytokines and nitric oxide. In this report we demonstrate that TGF-beta also attenuates the LPS-induced synthesis and secretion of prostaglandin E2 in murine RAW 264.7 macrophage cells. Macrophage activation also induces accumulation of the recently described ligand-responsive prostaglandin synthase (PGS) TIS10/PGS-2. While TGF-beta alone has no effect on expression from the TIS10/PGS-2 gene, this cytokine inhibits LPS-induced TIS10/PGS-2 protein accumulation and synthesis, as well as LPS-induced TIS10/PGS-2 message accumulation in RAW 264.7 cells. TGF-beta concentrations in the range of 0.1-1.0 ng/ml (4-40 pM) maximally inhibit LPS-induced TIS10/PGS-2 message accumulation. In contrast, neither LPS nor TGF-beta has any effect on the level of PGS-1 (EC 1.14.99.1) message. TGF-beta also attenuates LPS-induced accumulation of unspliced TIS10/PGS-2 transcripts in RAW 264.7 cells, suggesting that this cytokine exerts its effects on TIS10/PGS-2 expression at the transcriptional level. TGF-beta inhibits the LPS-induced accumulation of TIS10/PGS-2 protein and message in cultured murine peritoneal macrophages, as well as in macrophage cell lines.

  12. Prosurvival effect of cumulus prostaglandin G/H synthase 2/prostaglandin2 signaling on bovine blastocyst: impact on in vivo posthatching development†.

    PubMed

    Nuttinck, Fabienne; Jouneau, Alice; Charpigny, Gilles; Hue, Isabelle; Richard, Christophe; Adenot, Pierre; Ruffini, Sylvie; Laffont, Ludivine; Chebrout, Martine; Duranthon, Véronique; Guienne, Brigitte Marquant-Le

    2017-03-07

    Apoptotic activity is a common physiological process which culminates at the blastocyst stage in the preimplantation embryo of many mammals. The degree of embryonic cell death can be influenced by the oocyte microenvironment. However, the prognostic significance of the incidence of apoptosis remains undefined. Prostaglandin E2 (PGE2) derived from prostaglandin G/H synthase-2 (PTGS2) activity is a well-known prosurvival factor that is mainly studied in oncology. PGE2 is the predominant PTGS2-derived prostaglandin present in the oocyte microenvironment during the periconceptional period. Using an in vitro model of bovine embryo production followed by transfer and collection procedures, we investigated the impact of periconceptional PGE2 on the occurrence of spontaneous apoptosis in embryos and on subsequent in vivo posthatching development. Different periconceptional PGE2 environments were obtained using NS-398, a specific inhibitor of PTGS2 activity, and exogenous PGE2. We assessed the level of embryonic cell death in blastocysts at day 8 postfertilization by counting total cell numbers, by the immunohistochemical staining of active caspase-3, and by quantifying terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling signals and apoptosis regulator (BCL-2/BAX) mRNA expression. Morphometric parameters were used to estimate the developmental stage of the embryonic disk and the extent of trophoblast elongation on day 15 conceptuses. Our findings indicate that periconceptional PGE2 signaling durably impacts oocytes, conferring increased resistance to spontaneous apoptosis in blastocysts and promoting embryonic disk development and the elongation process during preimplantation development.

  13. Inhibition of microsomal prostaglandin E synthase-1 by aminothiazoles decreases prostaglandin E2 synthesis in vitro and ameliorates experimental periodontitis in vivo

    PubMed Central

    Kats, Anna; Båge, Tove; Georgsson, Pierre; Jönsson, Jörgen; Quezada, Hernán Concha; Gustafsson, Anders; Jansson, Leif; Lindberg, Claes; Näsström, Karin; Yucel-Lindberg, Tülay

    2013-01-01

    The potent inflammatory mediator prostaglandin E2 (PGE2) is implicated in the pathogenesis of several chronic inflammatory conditions, including periodontitis. The inducible enzyme microsomal prostaglandin E synthase-1 (mPGES-1), catalyzing the terminal step of PGE2 biosynthesis, is an attractive target for selective PGE2 inhibition. To identify mPGES-1 inhibitors, we investigated the effect of aminothiazoles on inflammation-induced PGE2 synthesis in vitro, using human gingival fibroblasts stimulated with the cytokine IL-1β and a cell-free mPGES-1 activity assay, as well as on inflammation-induced bone resorption in vivo, using ligature-induced experimental periodontitis in Sprague-Dawley rats. Aminothiazoles 4-([4-(2-naphthyl)-1,3-thiazol-2-yl]amino)phenol (TH-848) and 4-(3-fluoro-4-methoxyphenyl)-N-(4-phenoxyphenyl)-1,3-thiazol-2-amine (TH-644) reduced IL-1β-induced PGE2 production in fibroblasts (IC50 1.1 and 1.5 μM, respectively) as well as recombinant mPGES-1 activity, without affecting activity or expression of the upstream enzyme cyclooxygenase-2. In ligature-induced experimental periodontitis, alveolar bone loss, assessed by X-ray imaging, was reduced by 46% by local treatment with TH-848, compared to vehicle, without any systemic effects on PGE2, 6-keto PGF1α, LTB4 or cytokine levels. In summary, these results demonstrate that the aminothiazoles represent novel mPGES-1 inhibitors for inhibition of PGE2 production and reduction of bone resorption in experimental periodontitis, and may be used as potential anti-inflammatory drugs for treatment of chronic inflammatory diseases, including periodontitis.—Kats, A., Båge, T., Georgsson, P., Jönsson, J., Quezada, H. C., Gustafsson, A., Jansson, L., Lindberg, C., Näsström, K., Yucel-Lindberg, T. Inhibition of microsomal prostaglandin E synthase-1 by aminothiazoles decreases prostaglandin E2 synthesis in vitro and ameliorates experimental periodontitis in vivo. PMID:23447581

  14. Importance of adipocyte cyclooxygenase-2 and prostaglandin E2-prostaglandin E receptor 3 signaling in the development of obesity-induced adipose tissue inflammation and insulin resistance.

    PubMed

    Chan, Pei-Chi; Hsiao, Fone-Ching; Chang, Hao-Ming; Wabitsch, Martin; Hsieh, Po Shiuan

    2016-06-01

    We examined the involvement of adipocyte cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2)-prostaglandin E receptor (EP)3-mediated signaling during hypertrophy and hypoxia in the development of obesity-associated adipose tissue (AT) inflammation and insulin resistance. The experiments were conducted with high-fat diet (HFD)-induced obese rats, db/db mice, human subjects, and 3T3-L1 and the human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes; the groups were treated with selective inhibitors of COX-2 [celecoxib 30 mg/kg, half maximal inhibitory concentration (IC50) ≈ 0.04 µM] and EP3 (L-798106 100 µg/kg, IC50 ≈ 0.5 µM) or a short interfering RNA. There were strong, positive correlations between adipocyte COX-2 and EP3 gene expressions and the AT TNF-α and monocyte chemotactic protein-1 contents and the homeostatic model assessment for insulin resistance in HFD-induced obese rats, as well as body mass index in human subjects. Treatment with COX-2 and EP3 inhibitors significantly reversed AT inflammatory gene and protein expressions (-50%) and impaired glucose and insulin tolerance in db/db mice. COX-2 inhibition diminished the chemotaxis of adipocytes isolated from HFD rats to macrophages and T cells. Targeting inhibition of adipocyte COX-2 and EP3 during hypertrophy and hypoxia reversed the release of the augmented proinflammatory adipokines and the diminished adiponectin and also suppressed NF-κB and hypoxia-inducible factor-1α transcription activation. These findings suggest that adipocyte COX-2 PGE2-EP3-mediated signaling is crucially involved in the development of obesity-associated AT inflammation and insulin resistance.-Chan, P.-C., Hsiao, F.-C., Chang, H.-M., Wabitsch, M., Hsieh, P. S. Importance of adipocyte cyclooxygenase-2 and prostaglandin E2-prostaglandin E receptor 3 signaling in the development of obesity-induced adipose tissue inflammation and insulin resistance. © FASEB.

  15. A cross-sectional survey of the association between bilateral topical prostaglandin analogue use and ocular adnexal features.

    PubMed

    Shah, Mamta; Lee, Grace; Lefebvre, Daniel R; Kronberg, Benjamin; Loomis, Stephanie; Brauner, Stacey C; Turalba, Angela; Rhee, Douglas J; Freitag, Suzanne K; Pasquale, Louis R

    2013-01-01

    We studied the relation between prostaglandin analogue use and ocular adnexal features. We used a prospective, cross-sectional study involving 157 current, 15 past, and 171 never users of prostaglandin analogues. Patients 50 years of age or older and without conditions affecting ocular adnexal anatomy underwent glaucoma medication use history, external digital photography and systematic external adnexal exam. Two masked readers assessed the digital photos for upper lid dermatochalasis and lower lid steatoblepharon using a validated grading scheme. Another masked clinical examiner also assessed upper lid ptosis, levator muscle function, and inferior scleral show. We performed ordinal logistic regression analysis accounting for multiple covariates to assess the relation between prostaglandin analogue use and adnexal features. Multivariable analyses indicated there was a 230-fold increased risk of incremental involution of dermatochalasis (odds ratio (OR) = 2.30; 95% confidence interval (CI) 1.43-3.69; p = 5.44E-04) and a 249-fold increased risk of incremental loss of lower lid steatoblepharon (OR = 2.49; 95% CI, 1.54-4.03; p= 1.98E-04) associated with current prostaglandin analogue use (bimatoprost 0.03%, travoprost 0.005%, or latanoprost 0.004%) versus prostaglandin analogue never or past users. Upper lid ptosis (OR = 4.04; 95% CI, 2.43-6.72; p = 7.37E-08), levator dysfunction (OR = 7.51; 95% CI, 3.39-16.65; p = 6.74E-07) and lower lid retraction (OR = 2.60; 95% CI, 1.58-4.28; p = 1.72E-04) were highly associated with current prostaglandin analogue use versus prostaglandin analogue never or past users. The associations between prostaglandin analogue use and deepening of the upper lid sulci and between prostaglandin analogue use and loss of inferior periorbital fat are confirmed in this multivariable analysis. The associations between prostaglandin analogue use and levator muscle dysfunction and between prostaglandin analogue use and upper lid ptosis represent

  16. Implication of Prostaglandins and Histamine H1 and H2 Receptors in Radiation-Induced Temperature Responses of Rats

    DTIC Science & Technology

    1988-05-01

    1988) S Implication of Prostaglandins and Histamine H1 and H 2 Receptors in Radiation-Induced Temperature Responses of Rats SATHASIVA B. KANDASAMY ... KANDASAMY , S. B., HUNT. W. A., AND MICKLEY, G. A. Implications of Prostaglandins and Histamine H I and H2 Receptors in Radiation-Induced Temperature...lateral ventricle according to coordinates derived from the atlas of Pelligrino et al. (31): 0.8 mm posterior to bregma. 2.5 mm lateral. 44 KANDASAMY , HUNT

  17. Nonlinear Analyses of Elicited Modal, Raised, and Pressed Rabbit Phonation

    PubMed Central

    Awan, Shaheen N.; Novaleski, Carolyn K.; Rousseau, Bernard

    2014-01-01

    Objectives/Hypothesis The purpose of this study was to use nonlinear dynamic analysis methods such as phase space portraits and correlation dimension (D2) as well as descriptive spectrographic analyses to characterize acoustic signals produced during evoked rabbit phonation. Methods Seventeen New Zealand white breeder rabbits were used to perform the study. A Grass S-88 stimulator (SA Instrumentation, Encinitas, CA) and constant current isolation unit (Grass Telefactor, model PSIU6; West Warwick, RI) were used to provide electrical stimulation to laryngeal musculature, and transglottal airflow rate and stimulation current (mA) were manipulated to elicit modal, raised intensity, and pressed phonations. Central 1 second portions of the most stable portion of the acoustic waveform for modal, raised intensity, and pressed phonations were edited, and then analyzed via phase space portraits, Poincaré sections, and the estimation of the correlation dimension (D2). In an attempt to limit the effects of the highly variable and nonstationary characteristics of some of the signals being analyzed, D2 analysis was also performed on the most stable central 200 ms portion of the acoustic waveform. Descriptive analysis of each phonation was also conducted using sound spectrograms. Results Results showed that the complexity of phonation and the subsequent acoustic waveform is increased as transglottal airflow rate and degree of glottal adduction is manipulated in the evoked rabbit phonation model. In particular, phonatory complexity, as quantified via correlation dimension analyses and demonstrated via spectrographic characteristics, increases from “modal” (i.e., phonation elicited at just above the phonation threshold pressure) to raised intensity (phonation elicited by increasing transglottal airflow rate) to pressed (phonation elicited by increasing the stimulation current delivered to the larynx). Variations in a single dynamic dimension (airflow rate or adductory force

  18. Meclofenamate elicits a nephropreventing effect in a rat model of ischemic acute kidney injury by suppressing indoxyl sulfate production and restoring renal organic anion transporters

    PubMed Central

    Saigo, Chika; Nomura, Yui; Yamamoto, Yuko; Sagata, Masataka; Matsunaga, Rika; Jono, Hirofumi; Nishi, Kazuhiko; Saito, Hideyuki

    2014-01-01

    Indoxyl sulfate (IS), a putative low-molecular weight uremic toxin, is excreted in the urine under normal kidney function, but is retained in the circulation and tissues during renal dysfunction in acute kidney injury and chronic kidney disease. IS, which is one of the most potent inducers of oxidative stress in the kidney and cardiovascular system, is enzymatically produced in the liver from indole by cytochrome P450-mediated hydroxylation to indoxyl, followed by sulfotransferase-mediated sulfate conjugation. We used rat liver S9 fraction to identify inhibitors of IS production. After testing several compounds, including phytochemical polyphenols, we identified meclofenamate as a potent inhibitor of IS production with an apparent IC50 value of 1.34 μM. Ischemia/reperfusion (I/R) of rat kidney caused a marked elevation in the serum IS concentration 48 hours after surgery. However, intravenous administration of meclofenamate (10 mg/kg) significantly suppressed this increase in the serum level of IS. Moreover, IS concentrations in both kidney and liver were dramatically elevated by renal I/R treatment, but this increase was blocked by meclofenamate. Serum creatinine and blood urea nitrogen were markedly elevated in rats after renal I/R treatment, but these increases were significantly restored by administration of meclofenamate. Renal expression of both basolateral membrane-localized organic anion transporters rOAT1 and rOAT3 was downregulated by I/R treatment. However, expression of rOAT1 and rOAT3 recovered after administration of meclofenamate, which is associated with the inhibition of I/R-evoked elevation of prostaglandin E2. Our results suggest that meclofenamate inhibits hepatic sulfotransferase-mediated production of IS, thereby suppressing serum and renal accumulation of IS. Meclofenamate also prevents the prostaglandin E2-dependent downregulation of rOAT1 and rOAT3 expression. In conclusion, meclofenamate was found to elicit a nephropreventive effect in

  19. Changes in prostaglandin synthesis and metabolism associated with labour, and the influence of dexamethasone, RU 486 and progesterone.

    PubMed

    Brennand, J E; Leask, R; Kelly, R W; Greer, I A; Calder, A A

    1995-11-01

    The objective was to compare the changes in prostaglandin synthesis and metabolism occurring within the fetal membranes that are associated with the onset of parturition and to study the effect of steroid hormones on prostaglandin metabolism. A tissue explant study was made of discs of amnion and chorion obtained from 24 pregnant women at 37-42 weeks' gestation following spontaneous labour and delivery (12 women) and elective caesarean section (12 women). Significantly more prostaglandin E2 (PGE2) and PGF2 alpha were synthesized by amnion obtained following spontaneous labour than elective caesarean section. Arachidonic acid stimulated both PGE2 and PGF2 alpha synthesis by amnion in both groups. Phorbol myristoyl acetate stimulated PGE2 synthesis in both groups. There was no difference between the groups in the capacity of the chorion to metabolize prostaglandins. Mifepristone (RU 486) reduced the metabolism of added PGE2 following spontaneous labour, while dexamethasone and progesterone had no effect on prostaglandin metabolism. In conclusion, the increase in concentration of PGE2 and PGF2 alpha associated with the onset of spontaneous labour is the result of an increase in synthesis rather than a reduction in metabolism. There was no decrease in metabolism to account for the increase in prostaglandin concentrations and, with the exception of mifepristone, metabolism was not altered by the addition of steroid hormones.

  20. Stimulation of 86Rb+ and 32Pi movements in 3T3 cells by prostaglandins and phorbol esters.

    PubMed

    Moroney, J; Smith, A; Tomei, L D; Wenner, C E

    1978-06-01

    The potent tumor promoter tetradecanoyl phorbol acetate (TPA) induces early changes in ion movements analogous to those induced by prostaglandins E1 and F 2alpha. Among the earliest changes induced by TPA is a significant increase in 32Pi incorporation within 15 minutes incubation of TPA (10(-8)-10(-6) M) with post-confluent Swiss 3T3 mouse embryonic fibroblasts. Similarly, the active phorbol ester homolog 4-beta-OH phorbol didecanoate but not the inactive stereoisomeric 4-alpha-OH phorbol didecanoate stimulated 32Pi incorporation. Also, TPA at the above concentrations stimulated 86Rb+ influx shortly after administration. Both fluxes were ouabain-sensitive in accord with the idea that an early effect of TPA is to alter (Na+ + K+)-ATPase activity. Further, prostaglandin E1 (10(-7)-10(-6) M) and prostaglandin F 2alpha (3 X 10(-9)-10(-7) M) caused a similar stimulation of 86Rb+ and 32Pi uptake. The finding that water-soluble prostaglandin F 2alpha also exhibited stimulatory effects indicated that those hormone-induced responses are not mediated by solvent interactions. The similar responses of phorbol esters and prostaglandin derivatives suggests that phorbol esters and prostaglandin derivatives may act at common membrane sites. The finding that stimulatory effects were observed at discrete times in the logarithmic phase of growth suggests that the activation of membrane receptors may be cell-cycle dependent.

  1. An electron-capture gas–liquid-chromatographic method for the determination of prostaglandin F2α in biological fluids

    PubMed Central

    Wickramasinghe, Asoka J. F.; Shaw, Robert S.

    1974-01-01

    A sensitive electron-capture gas–liquid-chromatographic method for the determination of sub-nanogram quantities of prostaglandin F2α was developed. The method is based on the sub-microgram scale conversion of the prostaglandin into the electron-capturing pentafluorobenzyl ester, and analysis of the latter as the tris-trimethylsilyl ether. The lower limit of detection was 12.5pg of the ester injected `on-column' as the silylated product. The method was successfully applied to the determination of prostaglandin F2α in monkey plasma. The specificity of the analytical procedure was increased by incorporating a thin-layer chromatographic fractionation before gas–liquid chromatography. The utility of the analytical methodology developed was demonstrated by its application to the determination of plasma concentrations of intact prostaglandin F2α in a Rhesus monkey, after subcutaneous administration of a single dose of prostaglandin F2α. The electron-capture gas–liquid-chromatographic assay is compared with the radioimmunoassay and the gas–liquid-chromatographic–mass-spectrometry assay for the determination of prostaglandin F2α. PMID:4218093

  2. Does prostaglandin D2 hold the cure to male pattern baldness?

    PubMed

    Nieves, Ashley; Garza, Luis A

    2014-04-01

    Lipids in the skin are the most diverse in the entire human body. Their bioactivity in health and disease is underexplored. Prostaglandin D2 has recently been identified as a factor which is elevated in the bald scalp of men with androgenetic alopecia (AGA) and has the capacity to decrease hair lengthening. An enzyme which synthesizes it, prostaglandin D2 synthase (PTGDS or lipocalin-PGDS), is hormone responsive in multiple other organs. PGD2 has two known receptors, GPR44 and PTGDR. GPR44 was found to be necessary for the decrease in hair growth by PGD2 . This creates an exciting opportunity to perhaps create novel treatments for AGA, which inhibit the activity of PTGDS, PGD2 or GPR44. This review discusses the current knowledge surrounding PGD2 , and future steps needed to translate these findings into novel therapies for patients with AGA. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Molecular cloning and expression of rat prostaglandin E receptor EP2 subtype.

    PubMed

    Sando, T; Usui, T; Tanaka, I; Mori, K; Sasaki, Y; Fukuda, Y; Namba, T; Sugimoto, Y; Ichikawa, A; Narumiya, S

    1994-05-16

    A cDNA clone encoding the rat prostaglandin (PG) E receptor EP2 subtype was cloned from a rat lung cDNA library. It encodes 488 amino acid residues with putative seven-transmembrane domains. Specific binding of [3H]PGE2 was found in COS-7 cells transfected with the cDNA and was displaced with unlabeled prostaglandins in the order of PGE2 = PGE1 > iloprost > or = PGF2 alpha > or = PGD2. The binding was also inhibited by misoprostol, an EP2 and EP3 agonist, but not by sulprostone, an EP1 and EP3 agonist. Northern blot analysis demonstrated that the EP2 mRNA is widely expressed in various tissues, the significant expression being observed in the thymus, lung, spleen, heart stomach, and pancreas.

  4. Role of Prostaglandin Receptor EP2 in the Regulations of Cancer Cell Proliferation, Invasion, and Inflammation

    PubMed Central

    Dingledine, Ray

    2013-01-01

    Population studies, preclinical, and clinical trials suggest a role for cyclooxygenase-2 (COX-2, PTGS2) in tumor formation and progression. The downstream prostanoid receptor signaling pathways involved in tumorigenesis are poorly understood, although prostaglandin E2 (PGE2), a major COX-2 metabolite which is usually upregulated in the involved tissues, presumably plays important roles in tumor biology. Taking advantage of our recently identified novel selective antagonist for the EP2 (PTGER2) subtype of PGE2 receptor, we demonstrated that EP2 receptor activation could promote prostate cancer cell growth and invasion in vitro, accompanied by upregulation of the tumor-promoting inflammatory cytokines, such as IL-1β and IL-6. Our results suggest the involvement of prostaglandin receptor EP2 in cancer cell proliferation and invasion possibly via its inflammatory actions, and indicate that selective blockade of the PGE2-EP2 signaling pathway via small molecule antagonists might represent a novel therapy for tumorigenesis. PMID:23192657

  5. Role of prostaglandin receptor EP2 in the regulations of cancer cell proliferation, invasion, and inflammation.

    PubMed

    Jiang, Jianxiong; Dingledine, Ray

    2013-02-01

    Population studies, preclinical, and clinical trials suggest a role for cyclooxygenase-2 (COX-2, PTGS2) in tumor formation and progression. The downstream prostanoid receptor signaling pathways involved in tumorigenesis are poorly understood, although prostaglandin E2 (PGE(2)), a major COX-2 metabolite which is usually upregulated in the involved tissues, presumably plays important roles in tumor biology. Taking advantage of our recently identified novel selective antagonist for the EP2 (PTGER2) subtype of PGE(2) receptor, we demonstrated that EP2 receptor activation could promote prostate cancer cell growth and invasion in vitro, accompanied by upregulation of the tumor-promoting inflammatory cytokines, such as IL-1β and IL-6. Our results suggest the involvement of prostaglandin receptor EP2 in cancer cell proliferation and invasion possibly via its inflammatory actions, and indicate that selective blockade of the PGE(2)-EP2 signaling pathway via small molecule antagonists might represent a novel therapy for tumorigenesis.

  6. Lipocalin type prostaglandin D-synthase: which role in male fertility?

    PubMed

    Leone, Maria Grazia; Haq, Hanin Abdel; Saso, Luciano

    2002-04-01

    Lipocalin type prostaglandin-D-synthase (L-PGDS), also called beta-trace, is an extracellular protein very abundant in compartments beyond blood-tissue barriers, such as the cerebrospinal fluid, the aqueous humor, the amniotic fluid and the seminal fluid. In the latter fluid the major function of L-PGDS does not seem to be the synthesis of prostaglandin D(2) (PGD(2)) from its precursor PGH(2), which is very unstable in aqueous solution. Instead, seminal L-PGDS, an important carrier of bile pigments, retinoids, thyroid hormones and essential fatty acids, would contribute to providing, beyond the blood-testis barrier, thyroid hormones and retinoids to the developing germ cells in the seminiferous tubules and the maturing spermatozoa in the epididymis.

  7. Gas-liquid chromotography of trimethylsilyl and alkyl oxime-trimethylsilyl derivatives of some prostaglandins.

    PubMed

    Middleditch, B S; Desiderio, D M

    1972-08-01

    TMS (trimethylsilyl), MO-TMS (methyl oxime-TMS), and EO-TMS (ethyl oxime-TMS) derivatives of several prostaglandins (A, B1, B2, E1, 8-iso-E1, E2 and 8-iso-E2) were prepared and their gas chromatographic properties examined on a moderately polar (OV-17) and a relatively non-polar (SE-30) stationary phase. Combined gas chromatography-mass spectrometry (GC-MS) using an LKB 9000 instrument was used to identify the different derivatives. Although the TMS derivatives are more easily prepared, the TMS derivatives of the PgE series are thermally somewhat unstable. Thus, MO-TMS and EO-TMS derivatives which exhibit more regular retention increments are more useful for analytical work. The EO-TMS derivatives may be useful in determining mass spectral fragmentation modes of the prostaglandin derivatives.

  8. Cafeteria diet increases prostaglandin E2 levels in rat prostate, kidney and testis.

    PubMed

    Brunetti, L; Leone, S; Chiavaroli, A; Orlando, G; Recinella, L; Ferrante, C; Di Nisio, C; Verratti, V; Vacca, M

    2010-01-01

    Nutrient composition, particularly the omega-6/omega-3 polyunsaturated fatty acids ratio, may differently affect inflammatory mediators production in tissues, which could be causally related to increased cancer incidence in obesity. We evaluated prostaglandin E(2) levels in male Wistar rat prostate, kidney and testicle tissues after 15 days of either a high fat, cafeteria-style diet (5.50 Kcal/g, 30 percent calories from fat, omega-6/omega-3 ratio 2.33) or a standard laboratory chow diet (3.35 Kcal/g, 3 percent calories from fat, omega-6/omega-3 ratio 0.56). In the cafeteria diet compared to standard laboratory diet rats, we found both an increase in weight gain and increased prostaglandin E(2) (PGE(2)) levels in prostate, kidney and testicle tissues. The increased levels of PGE(2) induced by the cafeteria diet could drive an inflammatory process leading to increased incidence of prostate, kidney and testicular cancer in overweight patients.

  9. Inhibition of Mayaro virus replication by prostaglandin A(1) in Vero cells.

    PubMed

    Burlandy, F M; Rebello, M A

    2001-01-01

    Prostaglandins exhibit antiviral activity against a wide variety of RNA and DNA viruses. In the present report, we describe the effect of cyclopentenone prostaglandin A(1) (PGA(1)) on Mayaro virus replication in Vero cells. Virus yield was significantly reduced at nontoxic concentrations which did not suppress DNA, RNA or protein synthesis in uninfected or infected cells. Antiviral action decreased if PGA(1) was added at later times after infection. In Mayaro virus-infected cells, PGA(1) inhibited the synthesis of virus proteins. This effect is accompanied by the induction of heat shock proteins (HSPs). Actinomycin D treatment not only inhibited the induction of HSPs but also partially prevented PGA(1) antiviral activity.

  10. Involvement of nitric oxide, but not prostaglandins, in the vascular sympathoinhibitory effects of losartan in the pithed spontaneously hypertensive rat.

    PubMed Central

    Richer, C.; Domergue, V.; Vincent, M. P.; Giudicelli, J. F.

    1996-01-01

    1. The aim of this study was to investigate whether nitric oxide (NO) and/or vasodilator prostaglandins (PGs) are involved in the sympathoinhibitory effects exerted by losartan versus the vascular responses elicited by spinal cord electrical stimulation (SCS) in pithed spontaneously hypertensive rats (SHRs). 2. SHRs were given orally and for 8 days either losartan (10 mg kg-1 daily) or distilled water (controls). After pithing, blood pressure, heart rate, cardiac output, renal and muscular blood flows (pulsed Doppler technique) and the corresponding vascular resistance values were measured or calculated at baseline. Then, animals from both groups were given i.v. either saline, or NG-nitro-L-arginine methyl ester (L-NAME, 1 mg kg-1), or diclofenac (4 mg kg-1). Thereafter, haemodynamic parameters were determined in the six subgroups of animals in response (a) to SCS at increasing frequencies, and (b) to a noradrenaline bolus injection. 3. Losartan significantly decreased mean arterial pressure as well as renal and total peripheral resistances. In addition, losartan exhibited strong vascular sympathoinhibitory effects, significantly decreasing the systemic pressor and regional vasoconstrictor responses to SCS, but did not affect those to exogenous noradrenaline. In contrast, SCS-induced tachycardia was not modified by losartan. 4. L-NAME significantly increased total peripheral and regional vascular resistances but did not affect blood pressure and heart rate basal values. L-NAME potentiated the haemodynamic responses to SCS in control and, to a larger extent, in losartan-treated SHRs so that, with the exception of the renal vascular bed, the sympathoinhibitory effects of losartan were attenuated in all vascular beds studied. L-Arginine (300 mg kg-1) caused reversal of L-NAME effects in both control and losartan-treated SHRs. 5. Diclofenac did not affect the basal values of haemodynamic parameters in control and losartan-treated SHRs. Diclofenac potentiated the

  11. Inhibition of prostaglandin synthesis and its effect on uterine activity during established premature labor in sheep.

    PubMed

    Scott, J E; Grigsby, P L; Hirst, J J; Jenkin, G

    2001-01-01

    Continuous infusion of the selective prostaglandin synthase type-2 inhibitor nimesulide, together with the oxytocin receptor antagonist atosiban, inhibits glucocorticoid induction of labor in sheep. We evaluated the effectiveness of this treatment commencing after the onset of premature labor when prostaglandin concentrations are already significantly elevated. Premature labor was induced in chronically cannulated fetuses by constant fetal dexamethasone infusion. After the onset of active labor in each ewe, defined as uterine electromyographic (EMG) activity twice basal levels, ewes received combined nimesulide and atosiban (20.0 and 4.12 mg/kg per day, respectively; n = 6) or vehicle (n-methyl-2-pyrrolidone and saline each 1 mL/hour; n = 4) infusions for 48 hours. Maternal and fetal plasma PGFM (13,14-dihydro-15-keto PGF2alpha, the stable metabolite of prostaglandin (PG) F2alpha) and PGE2 concentrations were measured before, during, and after infusions. Four nimesulide- and atosiban-treated ewes successfully completed the 48-hour infusion period with no deliveries occurring during inhibitor treatment, or up to 6 hours after inhibitor treatment. Delivery was delayed in two other ewes, compared with control animals. Uterine EMG activity in nimesulide- and atosiban-treated ewes (n = 4) was significantly reduced during the 48-hour inhibitor treatment period. Maternal and fetal prostaglandin concentrations were significantly decreased in inhibitor-treated ewes during and after the infusions. The combination of nimesulide and atosiban treatment for 48 hours successfully inhibited the progression of active premature labor to delivery. This study further supports the potential value of this treatment regime for the inhibition of premature labor.

  12. Mechanical stimulation of skeletal muscle mitigates glucocorticoid induced decreases in prostaglandin synthesis

    NASA Technical Reports Server (NTRS)

    Chromiak, Joseph A.; Vandenburgh, Herman H.

    1993-01-01

    The glucocorticoid dexamethasone (Dex) induces a decline in protein synthesis and protein content of tissue cultured, avian skeletal muscle cells, and this atrophy is attenuated by repetitive mechanical stretch. Since the prostaglandin synthesis inhibitor indomethacin mitigated this stretch attenuation of muscle atrophy, the role of prostaglandins as growth modulators in these processes was examined. Dex at 10(exp -8) M reduced PGF(sub 2(alpha)) production 55 percent - 65 percent and PGE(sub 2) production 84 - 90 percent after 24 - 72 h of incubation in static cultures. Repetitive 10 percent stretch-relaxations of the non-Dex treated cultures increased PGF(sub 2(alpha)) efflux 41 percent at 24 h and 276 percent at 72 h and increased PGE(sub 2) production 51 percent at 24 h and 236 percent at 72 h. Mechanical stimulation of Dex treated cultures increased PGF(sub 2(alpha)) production 162 percent after 24 h, thus returning PGF(sub 2(alpha)) efflux to the level of non-Dex treated cultures. At 72 h, stretch increased PGF(sub 2(alpha)) efflux 65 percent in Dex treated cultures, but PGF(sub 2(alpha)) production was 45-84 percent less than non-Dex treated cultures. Mechanical stimulation of Dex treated cultures increased PGE(sub 2) production at 24 h, but not at 72 h. Dex reduced prostaglandin H synthase (PGHS) activity in the muscle cultures by 70 percent after 8 - 24 h of incubation, and mechanical stimulation increased PGHS activity of the Dex treated cultures by 98 percent. It is concluded that repetitive mechanical stimulation attenuates the catabolic effects of Dex on cultured skeletal muscle cells in part by reversing the Dex-induced declines in PGHS activity and prostaglandin production.

  13. MicroRNA and AU-rich element regulation of prostaglandin synthesis

    PubMed Central

    Moore, Ashleigh E.; Young, Lisa E.

    2012-01-01

    Many liness of evidence demonstrate that prostaglandins play an important role in cancer, and enhanced synthesis of prostaglandin E2 (PGE2) is often observed in various human malignancies often associated with poor prognosis. PGE2 synthesis is initiated with the release of arachidonic acid by phospholipase enzymes, where it is then converted into the intermediate prostaglandin prostaglandin H2 (PGH2) by members of the cyclooxygenase family. The synthesis of PGE2 from PGH2 is facilitated by three different PGE synthases, and functional PGE2 can promote tumor growth by binding to four EP receptors to activate signaling pathways that control cell proliferation, migration, apoptosis, and angiogenesis. An integral method of controlling gene expression is by posttranscriptional mechanisms that regulate mRNA stability and protein translation. Messenger RNA regulatory elements typically reside within the 3′ untranslated region (3′UTR) of the transcript and play a critical role in targeting specific mRNAs for posttranscriptional regulation through micro-RNA (miRNA) binding and adenylate- and uridylate-rich element RNA-binding proteins. In this review, we highlight the current advances in our understanding of the impact these RNA sequence elements have upon regulating PGE2 levels. We also identify various RNA sequence elements consistently observed within the 3′UTRs of the genes involved in the PGE2 pathway, indicating these binding sites for miRNAs and RNA-binding proteins to be central regulators of PGE2 synthesis and function. These findings may provide a rationale for the development of new therapeutic approaches to control tumor growth and metastasis promoted by elevated PGE2 levels. PMID:22005950

  14. Biochemical Warfare on the Reef: The Role of Glutathione Transferases in Consumer Tolerance of Dietary Prostaglandins

    PubMed Central

    Whalen, Kristen E.; Lane, Amy L.; Kubanek, Julia; Hahn, Mark E.

    2010-01-01

    Background Despite the profound variation among marine consumers in tolerance for allelochemically-rich foods, few studies have examined the biochemical adaptations underlying diet choice. Here we examine the role of glutathione S-transferases (GSTs) in the detoxification of dietary allelochemicals in the digestive gland of the predatory gastropod Cyphoma gibbosum, a generalist consumer of gorgonian corals. Controlled laboratory feeding experiments were used to investigate the influence of gorgonian diet on Cyphoma GST activity and isoform expression. Gorgonian extracts and semi-purified fractions were also screened to identify inhibitors and possible substrates of Cyphoma GSTs. In addition, we investigated the inhibitory properties of prostaglandins (PGs) structurally similar to antipredatory PGs found in high concentrations in the Caribbean gorgonian Plexaura homomalla. Principal Findings Cyphoma GST subunit composition was invariant and activity was constitutively high regardless of gorgonian diet. Bioassay-guided fractionation of gorgonian extracts revealed that moderately hydrophobic fractions from all eight gorgonian species examined contained putative GST substrates/inhibitors. LC-MS and NMR spectral analysis of the most inhibitory fraction from P. homomalla subsequently identified prostaglandin A2 (PGA2) as the dominant component. A similar screening of commercially available prostaglandins in series A, E, and F revealed that those prostaglandins most abundant in gorgonian tissues (e.g., PGA2) were also the most potent inhibitors. In vivo estimates of PGA2 concentration in digestive gland tissues calculated from snail grazing rates revealed that Cyphoma GSTs would be saturated with respect to PGA2 and operating at or near physiological capacity. Significance The high, constitutive activity of Cyphoma GSTs is likely necessitated by the ubiquitous presence of GST substrates and/or inhibitors in this consumer's gorgonian diet. This generalist's GSTs may

  15. Genotoxic properties of cyclopentenone prostaglandins and the onset of glutathione depletion.

    PubMed

    Solecki, Gergely Morten; Groh, Isabel Anna Maria; Kajzar, Julia; Haushofer, Carolin; Scherhag, Anne; Schrenk, Dieter; Esselen, Melanie

    2013-02-18

    Prostaglandins are endogenous mediators formed from arachidonic acid by cyclooxygenases and prostaglandin synthases during inflammatory processes. The five-membered ring can be dehydrated, and α,β-unsaturated cyclopentenone PGs (cyPGs) are generated. Recent studies have been focused on their potential pharmacological use against inflammation and cancer. However, little is known so far about possible adverse health effects of cyPGs. We addressed the question whether selected cyPGs at a concentration range of 0.1-10 μM exhibit mutagenic and genotoxic properties in the hamster lung fibroblast V79 cell line and whether these effects are accompanied by a depletion of intracellular glutathione (GSH). The cyPGs 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) and prostaglandin A2 (PGA2) significantly induced DNA damage in V79 cells after 1 h of incubation. Furthermore, a more pronounced increase in formamidopyrimidine-DNA glycosylase (FPG) sensitive sites, indicative of oxidative DNA-damage, was observed. The findings on DNA-damaging properties were supported by our results that 15dPGJ(2) acts as an aneugenic agent which induces the amount of kinetochore positive micronuclei associated with an increase of apoptosis. The strong potency of cyPGs to rapidly bind GSH measured in a chemical assay and to significantly reduce the GSH level after only 1 h of incubation may contribute to the observed oxidative DNA strand breaks, whereas directly induced oxidative stress via reactive oxygen species could be excluded. However, after an extended incubation time of 24 h no genotoxicity could be measured, this may contribute to the lack of mutagenicity in the hypoxanthine phosphorybosyltransferase (HPRT) assay. In conclusion, potential in vitro genotoxicity of cyPG and a strong impact on GSH homeostasis have been demonstrated, which may be involved in carcinogenesis mediated by chronic inflammation.

  16. Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins[S

    PubMed Central

    Subra, Caroline; Grand, David; Laulagnier, Karine; Stella, Alexandre; Lambeau, Gérard; Paillasse, Michael; De Medina, Philippe; Monsarrat, Bernard; Perret, Bertrand; Silvente-Poirot, Sandrine; Poirot, Marc; Record, Michel

    2010-01-01

    Exosomes are bioactive vesicles released from multivesicular bodies (MVB) by intact cells and participate in intercellular signaling. We investigated the presence of lipid-related proteins and bioactive lipids in RBL-2H3 exosomes. Besides a phospholipid scramblase and a fatty acid binding protein, the exosomes contained the whole set of phospholipases (A2, C, and D) together with interacting proteins such as aldolase A and Hsp 70. They also contained the phospholipase D (PLD) / phosphatidate phosphatase 1 (PAP1) pathway leading to the formation of diglycerides. RBL-2H3 exosomes also carried members of the three phospholipase A2 classes: the calcium-dependent cPLA2-IVA, the calcium-independent iPLA2-VIA, and the secreted sPLA2-IIA and V. Remarkably, almost all members of the Ras GTPase superfamily were present, and incubation of exosomes with GTPγS triggered activation of phospholipase A2 (PLA2)and PLD2. A large panel of free fatty acids, including arachidonic acid (AA) and derivatives such as prostaglandin E2 (PGE2) and 15-deoxy-Δ12,14-prostaglandinJ2 (15-d PGJ2), were detected. We observed that the exosomes were internalized by resting and activated RBL cells and that they accumulated in an endosomal compartment. Endosomal concentrations were in the micromolar range for prostaglandins; i.e., concentrations able to trigger prostaglandin-dependent biological responses. Therefore exosomes are carriers of GTP-activatable phospholipases and lipid mediators from cell to cell. PMID:20424270

  17. Oxygen resuscitation after hypoxia ischemia stimulates prostaglandin pathway in rat cortex

    PubMed Central

    Perez-Polo, J. Regino; Reilly, Conor B.; Rea, Harriet C.

    2011-01-01

    Exposure to hypoxia and hyperoxia in a rodent model of perinatal ischemia results in delayed cell death and and inflammation. Hyperoxia increases oxidative stress that can trigger inflammatory cascades, neutrophil activation, and brain microvascular injury. Here we show that 100% oxygen resuscitation in our rodent model of perinatal ischemia increases cortical COX-2 protein levels, S-nitrosylated COX-2cys526, PGE2, iNOS and 5-LOX, all components of the prostaglandin and leukotriene inflammatory pathway. PMID:21514373

  18. Toxin-Induced Activation of Rat Hepatocyte Prostaglandin Synthesis and Phospholipid Metabolism

    DTIC Science & Technology

    1989-12-22

    SUBJECT TERMS (Continue on reverse if necesay and identify by block number) FIELD GROUP SUB-GROUP - microcystin -LR, arachidonic acid, phospholipid...pool was reduced to 47% (p ɘ.025) by l’ 3’ microcystin -LR. Changes in phospholipid classes indicated that prostaglandin formation induced by microcystin ... microcystin -LR has important effects on the regulation of inflammatory mediator synthesis in hepatocytes. 7.,1 ,- TOXIN-INDUCED ACTIVATION OF RAT HEPATOCYTE

  19. Preliminary experience with 15 (S) 15-methyl prostaglandin F2 alpha for midtrimester abortion.

    PubMed

    Greer, B E; Droegemueller, W; Engel, T

    1975-02-15

    Twenty-six women received intramuscular or intra-amniotic 15 (S) 15-methyl prostaglandin F2 alpha to induce midtrimester abortion. The median initial injection-abortion interval was 10 hours and 25 minutes. The advantages of intramuscular analogue are somnolence and reduced discomfort during labor. Disadvantages include severe gastrointestinal toxicity in the majority of patients and symptoms of acute respiratory distress in two patients.

  20. Biochemical warfare on the reef: the role of glutathione transferases in consumer tolerance of dietary prostaglandins.

    PubMed

    Whalen, Kristen E; Lane, Amy L; Kubanek, Julia; Hahn, Mark E

    2010-01-06

    Despite the profound variation among marine consumers in tolerance for allelochemically-rich foods, few studies have examined the biochemical adaptations underlying diet choice. Here we examine the role of glutathione S-transferases (GSTs) in the detoxification of dietary allelochemicals in the digestive gland of the predatory gastropod Cyphoma gibbosum, a generalist consumer of gorgonian corals. Controlled laboratory feeding experiments were used to investigate the influence of gorgonian diet on Cyphoma GST activity and isoform expression. Gorgonian extracts and semi-purified fractions were also screened to identify inhibitors and possible substrates of Cyphoma GSTs. In addition, we investigated the inhibitory properties of prostaglandins (PGs) structurally similar to antipredatory PGs found in high concentrations in the Caribbean gorgonian Plexaura homomalla. Cyphoma GST subunit composition was invariant and activity was constitutively high regardless of gorgonian diet. Bioassay-guided fractionation of gorgonian extracts revealed that moderately hydrophobic fractions from all eight gorgonian species examined contained putative GST substrates/inhibitors. LC-MS and NMR spectral analysis of the most inhibitory fraction from P. homomalla subsequently identified prostaglandin A(2) (PGA(2)) as the dominant component. A similar screening of commercially available prostaglandins in series A, E, and F revealed that those prostaglandins most abundant in gorgonian tissues (e.g., PGA(2)) were also the most potent inhibitors. In vivo estimates of PGA(2) concentration in digestive gland tissues calculated from snail grazing rates revealed that Cyphoma GSTs would be saturated with respect to PGA(2) and operating at or near physiological capacity. The high, constitutive activity of Cyphoma GSTs is likely necessitated by the ubiquitous presence of GST substrates and/or inhibitors in this consumer's gorgonian diet. This generalist's GSTs may operate as 'all-purpose' detoxification

  1. [Seasonal changes in the influence of prostaglandin E2 on corticosteroid biosynthesis by rabbit adrenals].

    PubMed

    Bankova, V V; Kucherenko, A G; Markov, Kh M

    1975-03-01

    The biosynthesis of corticoids from exogenic tritated progesteron with and without addition of progstaglandin E2 in incubation medium was studied in rabbits in spring and in summer. C-14 inclusion into aldosteron, cortisone, and 11-dehydrocorticosterone in the spring rabbits was considerably higher than in the summer ones. Prostaglandin E2 suppressed the biosynthesis of the final fraction of corticosteroids in the spring rabbits and did not change the C-14 inclusion into corticosteroids in summer.

  2. Migraine: possible role of platelet insensitivity to prostaglandin E1 (PGE1).

    PubMed

    Cerneca, F; de Luyk, S; Radillo, O; Simeone, R; Mangiarotti, M

    1993-01-01

    Platelet aggregation inhibition, induced by prostaglandin E1 (PGE1), was evaluated in 38 patients affected by migraine. Our data indicate a complete insensitivity to PGE1 in these subjects. The insensitivity to PGE1 leads to decreased cyclic-AMP (cAMP) levels, determining an imbalance in the inhibitory mechanism. From this observation we can suppose that the decreased affinity of PGE1-receptors, causing decreased cAMP levels, may be involved in pathogenesis of migraine.

  3. Role of cytosolic phospholipase A2 in cytokine-stimulated prostaglandin release by human gallbladder cells.

    PubMed

    Grossmann, E M; Longo, W E; Mazuski, J E; Panesar, N; Kaminski, D L

    2000-01-01

    Eicosanoids are involved in gallbladder inflammation, epithelial water transport, and mucous secretion. Phospholipase Asubscript2 enzymes liberate arachidonic acid from membrane phospholipids for the synthesis of eicosanoids. The purpose of this study was to determine the effect of selective cytoplasmic and secretory phospholipase A2 inhibitors on basal and stimulated arachidonic acid and prostaglandin E2 release in gallbladder cells. Western immunoblotting was employed to evaluate both cytosolic and secretory phospholipase A2 enzymes in human gallbladder cells. Cells were incubated for 22 hours with (3)H-labeled arachidonic acid. Arachidonic acid and prostaglandin E2 release was then measured in the supernate after 2 hours of exposure to human interleukin-1beta, alone or after pretreatment for 1 hour with the inhibitors. Unstimulated gallbladder cells express both 85 kDa cytosolic and 14 kDa secretory phospholipase A2++. The 85 kDa phospholipase A2 was induced by interleukin-1beta, whereas there was no apparent change in secretory phospholipase A2 enzyme concentrations. Both the secretory phospholipase A2 inhibitor p-bromophenylacyl bromide and the cytosolic phospholipase A2 inhibitor arachidonyl trifluoromethyl ketone decreased basal and interleukin-1beta-stimulated arachidonic acid release. In contrast, only inhibition of cytosolic phospholipase A2 led to a decrease in interleukin-1beta-stimulated prostaglandin E2 release. Basal and interleukin-1beta-stimulated arachidonic acid release appears to be the result of the activity of both cytosolic and secretory phospholipase A2. Interleukin-1beta-stimulated prostaglandin E2 release appears to be dependent on the activity of cytosolic phospholipase A2.

  4. Deletion of microsomal prostaglandin E synthase-1 increases sensitivity to salt loading and angiotensin II infusion.

    PubMed

    Jia, Zhanjun; Zhang, Aihua; Zhang, Hui; Dong, Zheng; Yang, Tianxin

    2006-11-24

    Microsomal prostaglandin E synthase-1 (mPGES-1), a membrane-associated protein, is critically involved in the inflammatory response and may be involved in physiological processes as well. The present study examined the role of mPGES-1 in regulation of sodium balance and blood pressure in the settings of salt loading and angiotensin II infusion. mPGES-1 -/- mice developed severe and progressive hypertension associated with an inappropriate increase in sodium balance when fed a high-salt diet. These mice exhibited a significantly impaired ability to excrete an acute enteral load of NaCl. Under these 2 settings of salt loading, urinary excretion of prostaglandin E(2) and nitrate/nitrite were remarkably increased in wild-type animals but not in mPGES-1 -/- mice. The changes of urinary cGMP paralleled that of urinary nitrate/nitrite. mPGES-1 -/- mice exhibited a remarkable inhibition of high salt-induced increase in gene expression of all 3 NO synthase isoforms, whereas these mice had upregulated expression of NO synthase III but not NO synthase I and NO synthase II at basal state. Chronic salt loading remarkably induced mPGES-1 protein expression exclusively in the distal nephron. In primary cultures of CD cells, mPGES-1 expression was significantly increased following exposure to hypertonic NaCl, in parallel with increased prostaglandin E(2) release. These findings have revealed a mPGES-1/prostaglandin E(2)/NO/cGMP pathway that appears to be critically important for salt adaptation. In addition, we provide evidence that mPGES-1 deficiency sensitized the hypertensive effect of angiotensin II. Overall, this study has characterized the natriuretic and antihypertensive role of mPGES-1 that likely contributes to blood pressure homeostasis.

  5. Prostaglandin I2 Attenuates Prostaglandin E2-Stimulated Expression of Interferon γ in a β-Amyloid Protein- and NF-κB-Dependent Mechanism

    PubMed Central

    Wang, Pu; Guan, Pei-Pei; Yu, Xin; Zhang, Li-Chao; Su, Ya-Nan; Wang, Zhan-You

    2016-01-01

    Cyclooxygenase-2 (COX-2) has been recently identified as being involved in the pathogenesis of Alzheimer’s disease (AD). However, the role of an important COX-2 metabolic product, prostaglandin (PG) I2, in AD development remains unknown. Using mouse-derived astrocytes as well as APP/PS1 transgenic mice as model systems, we firstly elucidated the mechanisms of interferon γ (IFNγ) regulation by PGE2 and PGI2. Specifically, PGE2 accumulation in astrocytes activated the ERK1/2 and NF-κB signaling pathways by phosphorylation, which resulted in IFNγ expression. In contrast, the administration of PGI2 attenuated the effects of PGE2 on stimulating the production of IFNγ via inhibiting the translocation of NF-κB from the cytosol to the nucleus. Due to these observations, we further studied these prostaglandins and found that both PGE2 and PGI2 increased Aβ1–42 levels. In detail, PGE2 induced IFNγ expression in an Aβ1–42-dependent manner, whereas PGI2-induced Aβ1–42 production did not alleviate cells from IFNγ inhibition by PGI2 treatment. More importantly, our data also revealed that not only Aβ1–42 oligomer but also fibrillar have the ability to induce the expression of IFNγ via stimulation of NF-κB nuclear translocation in astrocytes of APP/PS1 mice. The production of IFNγ finally accelerated the deposition of Aβ1–42 in β-amyloid plaques. PMID:26869183

  6. Cyclooxygenase-2 and Prostaglandin E2 Signaling through Prostaglandin Receptor EP-2 Favor the Development of Myocarditis during Acute Trypanosoma cruzi Infection

    PubMed Central

    Guerrero, Néstor A.; Camacho, Mercedes; Vila, Luis; Íñiguez, Miguel A.; Chillón-Marinas, Carlos; Cuervo, Henar; Poveda, Cristina; Fresno, Manuel; Gironès, Núria

    2015-01-01

    Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2 was expressed by CD68+ myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11b+Ly6G- cells purified from infected heart tissue express COX-2 and produce prostaglandin E2 (PGE2) ex vivo. T. cruzi infections in COX-2 or PGE2-dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention. PMID:26305786

  7. Cyclooxygenase-2 and Prostaglandin E2 Signaling through Prostaglandin Receptor EP-2 Favor the Development of Myocarditis during Acute Trypanosoma cruzi Infection.

    PubMed

    Guerrero, Néstor A; Camacho, Mercedes; Vila, Luis; Íñiguez, Miguel A; Chillón-Marinas, Carlos; Cuervo, Henar; Poveda, Cristina; Fresno, Manuel; Gironès, Núria

    2015-01-01

    Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2 was expressed by CD68+ myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11b+Ly6G- cells purified from infected heart tissue express COX-2 and produce prostaglandin E2 (PGE2) ex vivo. T. cruzi infections in COX-2 or PGE2-dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention.

  8. The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis.

    PubMed

    Nishimura, Tomoyasu; Zhao, Xiaomin; Gan, Huixian; Koyasu, Shigeo; Remold, Heinz G

    2013-09-01

    Prostaglandin E2 (PGE2) is an important biological mediator involved in the defense against Mycobacterium tuberculosis (Mtb) infection. Previously, we reported that in macrophages (Mϕs), infection with avirulent Mtb H37Ra resulted in inhibition of necrosis by an inhibitory effect on mitochondrial permeability transition via the PGE2 receptor EP2. However, human Mϕs also express EP4, a PGE2 receptor functionally closely related to EP2 that also couples to stimulatory guanine nucleotide binding protein, but the functional differences between EP2 and EP4 in Mtb-infected Mϕs have been unclear. EP4 antagonist addition to H37Ra-infected Mϕs inhibited the expression of cyclooxygenase 2 (COX2) and microsomal prostaglandin E synthase-1 (mPGES-1), which are involved in PGE2 production. Moreover, H37Ra infection induced PGE2 production through the Toll-like receptor (TLR) 2/p38 mitogen-activated protein kinase (MAPK) signaling pathway. Induction of COX2 and mPGES-1 expression by TLR2 stimulation or Mtb infection was increased after additional stimulation with EP4 agonist. Hence, in Mtb-infected Mϕs, PGE2 production induced by pathogen recognition receptors/p38 MAPK signaling is up-regulated by EP4-triggered signaling to maintain an effective PGE2 concentration.

  9. Identification and characterization of the ocular hypotensive efficacy of travoprost, a potent and selective FP prostaglandin receptor agonist, and AL-6598, a DP prostaglandin receptor agonist.

    PubMed

    Hellberg, Mark R; McLaughlin, Marsha A; Sharif, Naj A; DeSantis, Louis; Dean, Tom R; Kyba, Evan P; Bishop, John E; Klimko, Peter G; Zinke, Paul W; Selliah, Robert D; Barnes, George; DeFaller, Joseph; Kothe, Angela; Landry, Theresa; Sullivan, E Kenneth; Andrew, Russell; Davis, Alberta A; Silver, Lewis; Bergamini, Michael V W; Robertson, Stella; Weiner, Alan L; Sallee, Verney L

    2002-08-01

    The structure-activity studies that led to the identification of travoprost, a highly selective and potent FP prostaglandin analog, and AL-6598, a DP prostaglandin analog, are detailed. In both series, the 1-alcohol analogs are very effective and are thought to be acting as prodrugs for the biologically active carboxylic acids. The efficacy of amide prodrugs depends on the degree of substitution and the size of the substituents. Selected compounds are profiled in vitro and in vivo preclinically. Clinical studies show that travoprost 0.004% (isopropyl ester) provided intraocular pressure control superior to timolol 0.5% when used as monotherapy in patients with open-angle glaucoma or ocular hypertension. In clinical studies, AL-6598 0.01% provided a sustained intraocular pressure reduction with q.d. application; b.i.d. provided greater intraocular pressure control. The acute and, apparently, conjunctival hyperemia associated with topical ocular AL-6598 can be attenuated while maintaining intraocular pressure-lowering efficacy by formulating with brimonidine.

  10. Emotional scenes and facial expressions elicit different psychophysiological responses.

    PubMed

    Alpers, Georg W; Adolph, Dirk; Pauli, Paul

    2011-06-01

    We examined if emotional faces elicit physiological responses similar to pictures of emotional scenes. Forty one students viewed emotional scenes (negative, neutral, and positive) and emotional faces (angry, neutral, and happy). Heart rate, orbicularis oculi and electrodermal activity were measured continuously, and the startle reflex was elicited. Although the patterns of valence and arousal ratings were comparable, physiological response patterns differed. For scenes we replicated the valence-specific modulation of the startle response, heart rate deceleration, and the arousal-related modulation of the electrodermal response. In contrast, for faces we found valence-specific modulation only for the electrodermal response, but the startle and heart rate deceleration were modulated by arousal. Although arousal differences may account for some differences in physiological responding this shows that not all emotional material that is decoded similarly leads to the same psychophysiological output. 2011 Elsevier B.V. All rights reserved.

  11. Simplified Expert Elicitation Procedure for Risk Assessment of Operating Events

    SciTech Connect

    Ronald L. Boring; David Gertman; Jeffrey Joe; Julie Marble; William Galyean; Larry Blackwood; Harold Blackman

    2005-06-01

    This report describes a simplified, tractable, and usable procedure within the US Nuclear Regulator Commission (NRC) for seeking expert opinion and judgment. The NRC has increased efforts to document the reliability and risk of nuclear power plants (NPPs) through Probabilistic Risk Assessment (PRA) and Human Reliability Analysis (HRA) models. The Significance Determination Process (SDP) and Accident Sequence Precursor (ASP) programs at the NRC utilize expert judgment on the probability of failure, human error, and the operability of equipment in cases where otherwise insufficient operational data exist to make meaningful estimates. In the past, the SDP and ASP programs informally sought the opinion of experts inside and outside the NRC. This document represents a formal, documented procedure to take the place of informal expert elicitation. The procedures outlined in this report follow existing formal expert elicitation methodologies, but are streamlined as appropriate to the degree of accuracy required and the schedule for producing SDP and ASP analyses.

  12. Expert elicitation for a national-level volcano hazard model

    NASA Astrophysics Data System (ADS)

    Bebbington, Mark; Stirling, Mark; Cronin, Shane; Wang, Ting; Jolly, Gill

    2016-04-01

    The quantification of volcanic hazard at national level is a vital pre-requisite to placing volcanic risk on a platform that permits meaningful comparison with other hazards such as earthquakes. New Zealand has up to a dozen dangerous volcanoes, with the usual mixed degrees of knowledge concerning their temporal and spatial eruptive history. Information on the 'size' of the eruptions, be it in terms of VEI, volume or duration, is sketchy at best. These limitations and the need for a uniform approach lend themselves to a subjective hazard analysis via expert elicitation. Approximately 20 New Zealand volcanologists provided estimates for the size of the next eruption from each volcano and, conditional on this, its location, timing and duration. Opinions were likewise elicited from a control group of statisticians, seismologists and (geo)chemists, all of whom had at least heard the term 'volcano'. The opinions were combined via the Cooke classical method. We will report on the preliminary results from the exercise.

  13. Conditioned craving cues elicit an automatic approach tendency.

    PubMed

    Van Gucht, Dinska; Vansteenwegen, Debora; Van den Bergh, Omer; Beckers, Tom

    2008-10-01

    In two experiments, we used a Pavlovian differential conditioning procedure to induce craving for chocolate. As a result of repeated pairing with chocolate intake, initially neutral cues came to elicit an automatic approach tendency in a speeded stimulus-response compatibility reaction time task. This automatic approach tendency, moreover, seemed to be sensitive to manipulations of extinction and renewal in the Pavlovian conditioning procedure. These findings corroborate and extend previous reports of automatic approach tendencies elicited by substance-relevant cues in addiction, while controlling for alternative accounts for such observations. Moreover, our data lend support to and extend learning models of cue-induced craving and addiction. Finally, we argue that the procedure we present here provides an ecologically valid behavioural tool that allows studying processes involved in cue-induced craving, addiction and relapse without relying on verbal report.

  14. Voltage transients elicited by sudden step-up of auxin

    NASA Technical Reports Server (NTRS)

    Pickard, B. G.

    1984-01-01

    It is hypothesized (i) that the molecular mechanism for the reception of friction and flexure and the mechanism by which auxin enhances ethylene production have in common a release of free calcium into the cytosol, (ii) that elevated cytosolic calcium initiates vesicle exocytosis, and (iii) that the vesicles release a factor or set of factors which depolarizes the plasmalemma and promotes ethylene synthesis. One consequence of such exocytosis should be small, extracellularly observable voltage transients. Transients, ranging in size up to 600 microvolts and possessing risetimes (10-90%) of approximately 200 ms, are known to be elicited in etiolated stems of Pisum sativum L. by friction and are here shown to be elicited by sudden increase of auxin concentration and also by a Ca2+ ionophore.

  15. Elicitation of specific syntactic structures in primary progressive aphasia.

    PubMed

    Deleon, Jessica; Gesierich, Benno; Besbris, Max; Ogar, Jennifer; Henry, Maya L; Miller, Bruce L; Gorno-Tempini, Maria Luisa; Wilson, Stephen M

    2012-12-01

    Many patients with primary progressive aphasia (PPA) are impaired in syntactic production. Because most previous studies of expressive syntax in PPA have relied on quantitative analysis of connected speech samples, which is a relatively unconstrained task, it is not well understood which specific syntactic structures are most challenging for these patients. We used an elicited syntactic production task to identify which syntactic structures pose difficulties for 31 patients with three variants of PPA: non-fluent/agrammatic, semantic and logopenic. Neurodegenerative and healthy age-matched participants were included as controls. As expected, non-fluent/agrammatic patients made the most syntactic errors. The structures that resulted in the most errors were constructions involving third person singular present agreement, and constructions involving embedded clauses. Deficits on this elicited production task were associated with atrophy of the left posterior inferior frontal gyrus.

  16. Eliciting probabilistic expectations: Collaborations between psychologists and economists

    PubMed Central

    Bruine de Bruin, Wändi

    2017-01-01

    We describe two collaborations in which psychologists and economists provided essential support on foundational projects in major research programs. One project involved eliciting adolescents’ expectations regarding significant future life events affecting their psychological and economic development. The second project involved eliciting consumers’ expectations regarding inflation, a potentially vital input to their investment, saving, and purchasing decisions. In each project, we sought questions with the precision needed for economic modeling and the simplicity needed for lay respondents. We identify four conditions that, we believe, promoted our ability to sustain these transdisciplinary collaborations and coproduce the research: (i) having a shared research goal, which neither discipline could achieve on its own; (ii) finding common ground in shared methodology, which met each discipline’s essential evidentiary conditions, but without insisting on its culturally acquired tastes; (iii) sharing the effort throughout, with common language and sense of ownership; and (iv) gaining mutual benefit from both the research process and its products. PMID:28270610

  17. Modified repetition in poems elicited from young children.

    PubMed

    Dowker, A D

    1991-10-01

    Attempts were made to elicit poems from 133 children between the ages of 2;3 and 6;11. Seventy-eight of the children produced 606 poems between them. Forty-five per cent of the poems contained the syntactic device of modified repetition: a substitution exercise where a grammatical frame is repeated and the substitution occurs in part of the grammatical frame. This was so despite the fact that modified repetition was not present in the examples that were used to elicit poems from the children. The frequency and types of modified repetition used by the children did not vary much with age. The question of whether children's use of modified repetition in their rhythmical poems has the function of helping them to practise grammatical forms, or whether it is simply one reflection of a general human tendency towards the use of pattern in language, is discussed.

  18. Elicitation of Diacetylenic Compounds in Suspension Cultured Cells of Eggplant

    PubMed Central

    Imoto, Setsuko; Ohta, Yoshimoto

    1988-01-01

    Induction of stress metabolites in the suspension cultured cells of eggplant (Solanum melongena L.) was examined. When autoclaved RNase A or nigeran, both of which are nonspecific phytoalexin elicitors in bean cells, were added to the cell culture of eggplant, greatly enhanced levels of three compounds were observed. One of them was cis-pentadeca-6-ene-1,3-diyne-5,15-diol, a novel diacetylenic compound. This compound has considerable fungitoxic activity. Also identified was falcarindiol, another fungitoxic diacetylenic compound previously reported as one of the phytoalexins in infected tomato fruits and leaves. Elicited compounds preferentially accumulated in the culture medium rather than in the cells and decreased to original levels during prolonged culturing. The elicitation of these compounds was closely correlated with cellular damage in terms of the decrease of growth rate and was inhibited by 10 micromolar cycloheximide. PMID:16665862

  19. The Frame Constraint on Experimentally Elicited Speech Errors in Japanese.

    PubMed

    Saito, Akie; Inoue, Tomoyoshi

    2017-06-01

    The so-called syllable position effect in speech errors has been interpreted as reflecting constraints posed by the frame structure of a given language, which is separately operating from linguistic content during speech production. The effect refers to the phenomenon that when a speech error occurs, replaced and replacing sounds tend to be in the same position within a syllable or word. Most of the evidence for the effect comes from analyses of naturally occurring speech errors in Indo-European languages, and there are few studies examining the effect in experimentally elicited speech errors and in other languages. This study examined whether experimentally elicited sound errors in Japanese exhibits the syllable position effect. In Japanese, the sub-syllabic unit known as "mora" is considered to be a basic sound unit in production. Results showed that the syllable position effect occurred in mora errors, suggesting that the frame constrains the ordering of sounds during speech production.

  20. AMORE; The Advanced Multimedia Organizer for Requirements Elicitation

    DTIC Science & Technology

    1993-06-01

    forth. Because large-scale systems may contain many thousands of requirements, it is necessary to provide some type of structural principles for...AMORE, it provides the tools necessary to: •Capture and preserve knowledge about the requirements elicitation process. • Teach useful skills that the...Tutor was based upon the principles of traditional instructional design and the orga- nization of lessons with prerequisite skills and objectives. A

  1. A Step-Wise Approach to Elicit Triangular Distributions

    NASA Technical Reports Server (NTRS)

    Greenberg, Marc W.

    2013-01-01

    Adapt/combine known methods to demonstrate an expert judgment elicitation process that: 1.Models expert's inputs as a triangular distribution, 2.Incorporates techniques to account for expert bias and 3.Is structured in a way to help justify expert's inputs. This paper will show one way of "extracting" expert opinion for estimating purposes. Nevertheless, as with most subjective methods, there are many ways to do this.

  2. Saturated Zone Flow and Transport Expert Elicitation Project

    SciTech Connect

    Coppersmith, Kevin J.; Perman, Roseanne C.

    1998-01-01

    This report presents results of the Saturated Zone Flow and Transport Expert Elicitation (SZEE) project for Yucca Mountain, Nevada. This project was sponsored by the US Department of Energy (DOE) and managed by Geomatrix Consultants, Inc. (Geomatrix), for TRW Environmental Safety Systems, Inc. The DOE's Yucca Mountain Site Characterization Project (referred to as the YMP) is intended to evaluate the suitability of the site for construction of a mined geologic repository for the permanent disposal of spent nuclear fuel and high-level radioactive waste. The SZEE project is one of several that involve the elicitation of experts to characterize the knowledge and uncertainties regarding key inputs to the Yucca Mountain Total System Performance Assessment (TSPA). The objective of the current project was to characterize the uncertainties associated with certain key issues related to the saturated zone system in the Yucca Mountain area and downgradient region. An understanding of saturated zone processes is critical to evaluating the performance of the potential high-level nuclear waste repository at Yucca Mountain. A major goal of the project was to capture the uncertainties involved in assessing the saturated flow processes, including uncertainty in both the models used to represent the physical processes controlling saturated zone flow and transport, and the parameter values used in the models. So that the analysis included a wide range of perspectives, multiple individual judgments were elicited from members of an expert panel. The panel members, who were experts from within and outside the Yucca Mountain project, represented a range of experience and expertise. A deliberate process was followed in facilitating interactions among the experts, in training them to express their uncertainties, and in eliciting their interpretations. The resulting assessments and probability distributions, therefore, provide a reasonable aggregate representation of the knowledge and

  3. Inflammatory mediators and nociception in the joint: excitation and sensitization of slowly conducting afferent fibers of cat's knee by prostaglandin I2.

    PubMed

    Schepelmann, K; Messlinger, K; Schaible, H G; Schmidt, R F

    1992-09-01

    The effects of prostaglandin I2 on the discharge properties of fine articular afferents (group III and group IV fibers) in the cat were examined by extracellular recordings from single units dissected from the medial articular nerve of the knee joint. Prostaglandin I2 was applied intra-arterially close to the joint in doses of 0.3-30 micrograms per 0.3 ml bolus injection, and its effects on the spontaneous activity as well as on discharges evoked by mechanical and chemical stimulation (bradykinin) were monitored. Prostaglandin E2 was also applied and the effects of prostaglandins I2 and E2 on particular units were compared. An excitatory effect of prostaglandin I2 was observed in 49% of 37 group III and in 37% of 27 group IV units. A sensitization to passive movements of the joint occurred in 71% of 31 group III and 48% of 21 group IV units. Sixty-seven per cent of 32 units (groups III and IV) were both excited and sensitized by prostaglandin I2 to movements of 27% were sensitized but not excited. In 64% of 11 group III and 63% of eight group IV units studied the responses to bradykinin were enhanced by prostaglandin I2. Prostaglandin E2 had qualitatively similar effects as prostaglandin I2 but excited and sensitized a lower proportion of articular afferents. Forty-one per cent of the units were sensitive to both prostaglandins but 26% of the fibers were only sensitive to prostaglandin I2. None of the units was exclusively sensitive to prostaglandin E2. In general, the excitatory and sensitizing effects of prostaglandin E2 had a longer duration than those exerted by prostaglandin I2. We conclude that prostaglandin I2 increases the sensitivity to mechanical stimuli as well as to chemical stimulation by bradykinin in the majority of articular group III and group IV fibers. Moreover, in a large proportion of articular afferents, prostaglandin I2 had an excitatory effect. Thus, prostaglandin I2 may be an inflammatory mediator which is important for inflammation

  4. Monocyte prostaglandins inhibit procollagen secretion by human vascular smooth muscle cells: implications for plaque stability.

    PubMed

    Fitzsimmons, C; Proudfoot, D; Bowyer, D E

    1999-02-01

    Extracellular matrix remodelling occurs during atherosclerosis dictating the structure of the plaque and thus the resistance to rupture. Monocytes and macrophages are believed to play a role in this remodelling. In the present study, filter-separated co-culture has been used to study the effect of monocytes on procollagen turnover by human vascular smooth muscle cells (VSMC). In this system, freshly isolated human peripheral blood monocytes inhibited procollagen secretion from VSMC without affecting either degradation of procollagen, or DNA synthesis by the VSMC. Insertion of a 12 kDa dialysis membrane between the two cell types and treatment with indomethacin showed that the inhibitory factor was of low molecular weight and was cyclooxygenase-dependent. Pre-incubation of each cell type with indomethacin demonstrated that monocyte, but not VSMC cyclooxygenase was required. Thus, the inhibitory effect on procollagen secretion was due, most likely, to monocyte prostaglandins. Neither inhibition of thromboxane synthetase, nor blocking IL-1 activity, reduced the inhibitory activity. Addition of prostaglandins PGE1, PGE2 and PGF2alpha to VSMC cultures caused a reduction in procollagen secretion which was equivalent to, but was not additive with, the maximal effect achieved by monocytes. Monocytes and macrophages are a major source of prostaglandins and these molecules are likely to play an important role in collagen turnover within lesions.

  5. Lipopolysaccharide reduces food passage rate from the crop by a prostaglandin-independent mechanism in chickens.

    PubMed

    Tachibana, T; Ogino, M; Makino, R; Khan, M S I; Cline, M A

    2017-02-01

    1. We examined the effect of lipopolysaccharide (LPS), a component of Gram-negative bacteria, on food passage in the digestive tract of chickens (Gallus gallus) in order to clarify whether bacterial infection affects food passage in birds. 2. Food passage in the crop was significantly reduced by intraperitoneal (IP) injection of LPS while it did not affect the number of defecations, suggesting that LPS may affect food passage only in the upper digestive tract. 3. Similar to LPS, prostaglandin E2 (PGE2), one of the mediators of LPS, also reduced crop-emptying rate in chickens while it had no effect on the number of defecations. 4. Pretreatment with indomethacin, which is an inhibitor of cyclooxygenase (COX), a prostaglandin synthase, had no effect on LPS-induced inhibition of crop emptying. 5. IP injection of LPS did not affect the mRNA expression of COX2 in the upper digestive tract of chickens. 6. It is therefore likely that LPS and PGE2 reduced food passage rate in the crop by a prostaglandin-independent pathway in chickens.

  6. Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment[S

    PubMed Central

    Hu, Xiaoqian; Cifarelli, Vincenza; Sun, Shishuo; Kuda, Ondrej; Abumrad, Nada A.; Su, Xiong

    2016-01-01

    Obesity induces accumulation of adipose tissue macrophages (ATMs), which contribute to both local and systemic inflammation and modulate insulin sensitivity. Adipocyte lipolysis during fasting and weight loss also leads to ATM accumulation, but without proinflammatory activation suggesting distinct mechanisms of ATM recruitment. We examined the possibility that specific lipid mediators with anti-inflammatory properties are released from adipocytes undergoing lipolysis to induce macrophage migration. In the present study, we showed that conditioned medium (CM) from adipocytes treated with forskolin to stimulate lipolysis can induce migration of RAW 264.7 macrophages. In addition to FFAs, lipolytic stimulation increased release of prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2), reflecting cytosolic phospholipase A2 α activation and enhanced cyclooxygenase (COX) 2 expression. Reconstituted medium with the anti-inflammatory PGE2 potently induced macrophage migration while different FFAs and PGD2 had modest effects. The ability of CM to induce macrophage migration was abolished by treating adipocytes with the COX2 inhibitor sc236 or by treating macrophages with the prostaglandin E receptor 4 antagonist AH23848. In fasted mice, macrophage accumulation in adipose tissue coincided with increases of PGE2 levels and COX1 expression. Collectively, our data show that adipocyte-originated PGE2 with inflammation suppressive properties plays a significant role in mediating ATM accumulation during lipolysis. PMID:26912395

  7. Multiple roles of the prostaglandin D2 signaling pathway in reproduction.

    PubMed

    Rossitto, Moïra; Ujjan, Safdar; Poulat, Francis; Boizet-Bonhoure, Brigitte

    2015-01-01

    Prostaglandins signaling molecules are involved in numerous physiological processes. They are produced by several enzyme-limited reactions upon fatty acids, which are catalyzed by two cyclooxygenases and prostaglandin synthases. In particular, the prostaglandins E2 (PGE2), D2 (PGD2), and F2 (PGF2 α) have been shown to be involved in female reproductive mechanisms. Furthermore, widespread expression of lipocalin- and hematopoietic-PGD2 synthases in the male reproductive tract supports the purported roles of PGD2 in the development of both embryonic and adult testes, sperm maturation, and spermatogenesis. In this review, we summarize the putative roles of PGD2 signaling and the roles of both PGD2 synthases in testicular formation and function. We review the data reporting the involvement of PGD2 signaling in the differentiation of Sertoli and germ cells of the embryonic testis. Furthermore, we discuss the roles of lipocalin-PGD2 synthase in steroidogenesis and spermatogenesis, in terms of lipid molecule transport and PGD2 production. Finally, we discuss the hypothesis that PGD2 signaling may be affected in certain reproductive diseases, such as infertility, cryptorchidism, and testicular cancer.

  8. Protective effects of prostaglandins in the isolated gastric mucosa of the eel, Anguilla anguilla.

    PubMed

    Faggio, C; Denaro, M G; Lionetto, M G; Trischitta, F

    2000-09-01

    The protective effect of endogenous prostaglandins on the fish gastric mucosa was evaluated by studying the effect of indomethacin and aspirin, known cyclooxigenase inhibitors, on the mucosal ulceration in the isolated gastric sacs of Anguilla anguilla. Gastric sacs devoid of muscle layers were incubated in the presence of indomethacin (10(-4) mol x l(-1)) or aspirin (10(-4) mol x l(-1)) in different experimental conditions. Both the antiinflammatory drugs produced ulcers, but the effects were more severe in the presence of histamine and in the absence of HCO3- in the incubation bath. The effects of prostaglandin E2 (PGE2) on acid secretion rate (J(H)) and on alkaline secretion rate (J(OH)) were evaluated (with the aid of the pH stat method) in isolated gastric mucosa mounted in Ussing chambers. We found that PGE2 (10(-8)-10(-5) mol x l(-1)) increased JH in a dose-dependent manner. In tissues pretreated with luminal omeprazole (10(-4) mol x l(-1)), PGE2 stimulated gastric alkaline secretion. It was nullified by serosal removal of HCO3- or Na+ and by serosal ouabain (10(-4) mol x l(-1)). These results suggested that prostaglandins also exert their protective effects in fish gastric mucosa. This protection seems partially due to a stimulation of exogenous HCO3- transport from the serosal to the mucosal side. It is likely that this transport is an active transcellular mechanism coupled to Na+ transport.

  9. Prostaglandin E2 EP receptors as therapeutic targets in breast cancer.

    PubMed

    Reader, Jocelyn; Holt, Dawn; Fulton, Amy

    2011-12-01

    Prostaglandins are lipid compounds that mediate many physiological effects. Prostaglandin E2 (PGE(2)) is the most abundant prostanoid in the human body, and synthesis of PGE(2) is driven by cyclooxygenase enzymes including COX-2. Both elevated expression of COX-2 and increased PGE(2) levels have been associated with many cancers including breast cancer. PGE(2) exerts its effect by binding to the E series of prostaglandin receptors (EP) which are G protein-coupled receptors. Four EP receptor subtypes exist, EP1-4, and each is coupled to different intracellular signaling pathways. As downstream effectors of the COX-2 pathway, EP receptors have been shown to play a role in breast and other malignancies and in cancer metastasis. The role of each EP receptor in malignant behavior is complex and involves the interplay of EP receptor signaling on the tumor cell, on stromal cells, and on host immune effector cells. While preclinical and epidemiological data support the use of nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors (COXibs) for the prevention and treatment of malignancy, toxicities due to COXibs as well as less than promising results from clinical trials have laboratories seeking alternative targets. As knowledge concerning the role of EP receptors in cancer grows, so does the potential for exploiting EP receptors as therapeutic targets for the treatment or prevention of cancer and cancer metastasis.

  10. Prostaglandin E2 EP Receptors as Therapeutic Targets in Breast Cancer

    PubMed Central

    Reader, Jocelyn; Holt, Dawn; Fulton, Amy

    2011-01-01

    Prostaglandins are lipid compounds that mediate many physiological effects. Prostaglandin E2 (PGE2) is the most abundant prostanoid in the human body and synthesis of PGE2 is driven by cyclooxygenase enzymes including COX-2. Both elevated expression of COX-2 and increased PGE2 levels have been associated with many cancers including breast cancer. PGE2 exerts its effect by binding to the E series of prostaglandin receptors (EP) which are G-protein coupled receptors (GPCRs). Four EP receptor subtypes exist, EP1–4, and each are coupled to different intracellular signaling pathways. As downstream effectors of the COX-2 pathway, EP receptors have been shown to play a role in breast and other malignancies and in cancer metastasis. The role of each EP receptor in malignant behavior is complex and involves the interplay of EP receptor signaling on the tumor cell, on stromal cells and on host immune effector cells. While preclinical and epidemiological data support the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (COXibs) for the prevention and treatment of malignancy, toxicities due to COXibs as well as less than promising results from clinical trials have laboratories seeking alternative targets. As knowledge concerning the role of EP receptors in cancer grows, so does the potential for exploiting EP receptors as therapeutic targets for the treatment or prevention of cancer and cancer metastasis. PMID:22002714

  11. Muscle sympathetic nerve responses to physiological changes in prostaglandin production in humans

    NASA Technical Reports Server (NTRS)

    Doerzbacher, K. J.; Ray, C. A.

    2001-01-01

    Previous studies suggest that prostaglandins may contribute to exercise-induced increases in muscle sympathetic nerve activity (MSNA). To test this hypothesis, MSNA was measured at rest and during exercise before and after oral administration of ketoprofen, a cyclooxygenase inhibitor, or placebo. Twenty-one subjects completed two bouts of graded dynamic and isometric handgrip to fatigue. Each exercise bout was followed by 2 min of postexercise muscle ischemia. The second exercise bouts were performed after 60 min of rest in which 11 subjects were given ketoprofen (300 mg) and 10 subjects received a placebo. Ketoprofen significantly lowered plasma thromboxane B(2) in the drug group (from 36 +/- 6 to 22 +/- 3 pg/ml, P < 0.04), whereas thromboxane B(2) in the placebo group increased from 40 +/- 5 to 61 +/- 9 pg/ml from trial 1 to trial 2 (P < 0.008). Ketoprofen and placebo did not change sympathetic and cardiovascular responses to dynamic handgrip, isometric handgrip, and postexercise muscle ischemia. There was no relationship between thromboxane B(2) concentrations and MSNA or arterial pressure responses during both exercise modes. The data indicate that physiological increases or decreases in prostaglandins do not alter exercise-induced increases in MSNA and arterial pressure in humans. These findings suggest that contraction-induced metabolites other than prostaglandins mediate MSNA responses to exercise in humans.

  12. Macrophages programmed by apoptotic cells promote angiogenesis via prostaglandin E2.

    PubMed

    Brecht, Kerstin; Weigert, Andreas; Hu, Jiong; Popp, Rüdiger; Fisslthaler, Beate; Korff, Thomas; Fleming, Ingrid; Geisslinger, Gerd; Brüne, Bernhard

    2011-07-01

    Macrophages contribute to tissue homeostasis in the developing as well as the adult organism. They promote tissue regeneration and remodeling after injury, which requires efficient neoangiogenesis. Signaling pathways activating an angiogenic program in macrophages are still poorly defined. We report that apoptotic cells (ACs), which originate from stressed or damaged tissues, can induce angiogenic properties in primary human macrophages. The signal originating from ACs is the lipid mediator sphingosine-1-phosphate (S1P), which activates S1P1/3 on macrophages to up-regulate cyclooxygenase-2. The formation and liberation of prostaglandin E(2) (PGE(2)) then stimulates migration of endothelial cells. This is demonstrated by using PGE(2) receptor antagonists or a neutralizing PGE(2) antibody in vitro, thereby attenuating endothelial cell migration using a Boyden chamber assay. In vivo, neutralization of PGE(2) from proangiogenic macrophage supernatants blocked vessel formation into Matrigel plugs. In particular, apoptotic cancer cells shifted prostanoid formation in macrophages selectively toward PGE(2) by up-regulating cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (mPGES1), while down-regulating the PGE(2)-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) or prostaglandin-D synthase (PGDS). Angiogenic programming of macrophages by ACs, therefore, may control responses to tissue stress such as in tumors, where macrophages support cancer progression.

  13. A randomized clinical trial comparing misoprostol with prostaglandin E2 gel for preinduction cervical ripening.

    PubMed

    Gottschall, D S; Borgida, A F; Mihalek, J J; Sauer, F; Rodis, J F

    1997-11-01

    Our purpose was to perform a randomized trial comparing intravaginal misoprostol to intravaginal prostaglandin E2 gel for preinduction cervical ripening evaluating efficacy and side effects. Seventy-five women seen for induction of labor were randomized to receive 100 micrograms of intravaginal misoprostol or 5 mg of pharmacy-prepared intravaginal prostaglandin E2 gel for cervical ripening before oxytocin induction. Six hours after placement of the study agent, patients were given oxytocin if they were not in labor. The primary outcome measure was induction-to-delivery time; secondary measures were change in Bishop score, delivery mode, and side effects. Results were analyzed by the Student t test and Fisher's exact test, with p < 0.05 considered significant. There was no difference in the incidence of primiparity or the median initial Bishop score between the two study groups. The mean time to delivery and the need for oxytocin was significantly less for subjects receiving misoprostol. There was no difference in the incidence of uterine hyperstimulation syndrome or cesarean delivery between the groups. This randomized clinical trial indicates that misoprostol is efficacious for preinduction cervical ripening. Misoprostol use resulted in a significantly shorter induction-to-delivery time compared with prostaglandin E2 gel use. The side effects associated with misoprostol may be dose related, and further studies to identify the optimum dosage and interval are needed.

  14. Lipopolysaccharide reduces food passage rate from the crop by a prostaglandin-independent mechanism in chickens

    PubMed Central

    Tachibana, T.; Ogino, M.; Makino, R.; Khan, M. S. I.; Cline, M. A.

    2017-01-01

    ABSTRACT 1. We examined the effect of lipopolysaccharide (LPS), a component of Gram-negative bacteria, on food passage in the digestive tract of chickens (Gallus gallus) in order to clarify whether bacterial infection affects food passage in birds. 2. Food passage in the crop was significantly reduced by intraperitoneal (IP) injection of LPS while it did not affect the number of defecations, suggesting that LPS may affect food passage only in the upper digestive tract. 3. Similar to LPS, prostaglandin E2 (PGE2), one of the mediators of LPS, also reduced crop-emptying rate in chickens while it had no effect on the number of defecations. 4. Pretreatment with indomethacin, which is an inhibitor of cyclooxygenase (COX), a prostaglandin synthase, had no effect on LPS-induced inhibition of crop emptying. 5. IP injection of LPS did not affect the mRNA expression of COX2 in the upper digestive tract of chickens. 6. It is therefore likely that LPS and PGE2 reduced food passage rate in the crop by a prostaglandin-independent pathway in chickens. PMID:27871194

  15. Localization of platelet prostaglandin production in the platelet dense tubular system.

    PubMed Central

    Gerrard, J. M.; White, J. G.; Rao, G. H.; Townsend, D.

    1976-01-01

    Platelet production of 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9, 12L-dihydroxy-5,10-heptadecadienoic acid (PHD), two metabolites of the prostaglandin cyclic endoperoxides PGG2 and PGH2, was found in this investigation to occur primarily in a platelet microsomal fraction consisting almost exclusively of membranes. To further localize the membrane site of platelet prostaglandin biosynthesis, the present study has used a cytochemical technique employing 3,3'-diaminobenzidine as an oxidizable substrate. The reaction product was found to localize in the platelet dense tubular system. Formation of the reaction product was inhibited by aminotriazole. In similar concentrations, aminotriazole inhibited collagen and arachidonic acid aggregation, the second wave of ADP and epinephrine aggregation, but failed to inhibit aggregation by PGG2 and A23187. A study of the mechanism of action of aminotriazole revealed inhibition of formation of HHT and PHD. The results localize platelet prostaglandin biosynthesis to the membranes of the dense tubular system. Images Figure 5 Figure 6 Figures 1-2 Figure 3 and 4 PMID:1266944

  16. Differential effect of acetylsalicylic acid and dipyrone on prostaglandin production in human fibroblast cultures.

    PubMed Central

    Lüthy, C.; Multhaupt, M.; Oetliker, O.; Perisic, M.

    1983-01-01

    Human skin fibroblasts incubated with arachidonic acid in culture show basal release of prostaglandins. They produce the same prostaglandins after stimulation with bradykinin. Basal release of prostaglandins I2 (6-oxo-PGF1 alpha), F2 alpha and E2 is inhibited dose-dependently by both acetylsalicylic acid (ASA) and dipyrone (P less than 0.05). The examined dose-range was 10(-7) to 10(-4) M for both drugs. During the first 5 min after removal of the drugs from the incubation medium, bradykinin-stimulated release remains dose-dependently inhibited (P less than 0.001) in ASA-, but not in dipyrone-treated cultures. The difference between the effects of ASA and of dipyrone is highly significant (P less than 0.0001), whereas the dipyrone-treated cultures are not different from controls. The findings are consistent with cyclo-oxygenase inhibition by ASA as well as by dipyrone. However, the data demonstrate rapid reversibility of the effect of dipyrone. This suggests that in contrast to ASA, dipyrone does not inhibit cyclo-oxygenase by binding covalently to the enzyme. PMID:6418250

  17. Molecular cloning and characterization of the canine prostaglandin E receptor EP2 subtype.

    PubMed

    Hibbs, T A; Lu, B; Smock, S L; Vestergaard, P; Pan, L C; Owen, T A

    1999-05-01

    Prostaglandin E2 (PGE2) binds to four G-protein coupled cell surface receptors (EP1-EP4) and has been implicated as a local mediator of bone anabolism via a cyclic AMP mediated pathway following activation of the EP2 and/or EP4 receptor subtype. A canine kidney cDNA library was screened using a human EP2 probe, and a clone with an open reading frame of 1083 bp, potentially encoding a protein of 361 amino acids, was characterized. This open reading frame has 89% identity to the human EP2 cDNA at the nucleotide level and 87% identity at the predicted protein level. Scatchard analysis of a CHO cell line stably transfected with canine EP2 yielded a dissociation constant of 22 nM for PGE2. Competition binding studies, using 3H-PGE2 as ligand, demonstrated specific displacement by PGE2, Prostaglandin E1, Prostaglandin A3, and butaprost (an EP2 selective ligand), but not by ligands with selectivity for the related DP, FP, IP, or TP receptors. Specific ligand binding also resulted in increased levels of cAMP in EP2 transfected cells with no evidence of short-term, ligand-induced desensitization. Northern blot analysis revealed two transcripts of 3300 and 2400 bp in canine lung, and reverse-transcription polymerase chain reaction showed expression in all tissues examined. Southern blot analysis suggests the presence of a single-copy gene for EP2 in the dog.

  18. Comparison of effects of aspirin and indomethacin on human platelet prostaglandin synthetase.

    PubMed Central

    Crook, D; Collins, A J

    1977-01-01

    Human platelets were incubated in vitro with either aspirin or indomethacin and the prostaglandin synthetase activity of the resultant microsomal fraction from each incubation measured using a radiometric technique. Whereas aspirin produced a dose-related inhibition of the enzyme, indomethacin produced little or no inhibition over the same concentration range (10(-6) mol/l--10(-3) mol/l). Furthermore, administration of aspirin (600 mg) to volunteers produced a highly significant, prolonged inhibition of platelet microsomal prostaglandin synthetase whereas no inhibition was found with indomethacin (50 mg). As indomethacin is considerably more potent than aspirin as an inhibitor of human platelet prostaglandin synthetase in vitro, the results suggest a fundamental difference in the nature of the inhibition produced by each drug, aspirin being an essentially irreversible inhibitor whereas the inhibition produced by indomethacin is reversible. Studies with [3H-acetyl] aspirin have confirmed previous findings (Roth and Majerus, 1975) that aspirin produces an irreversible acetylation of a particulate fraction protein from human platelets. PMID:411427

  19. Gastroprotective Effect of Geopropolis from Melipona scutellaris Is Dependent on Production of Nitric Oxide and Prostaglandin

    PubMed Central

    Ribeiro-Junior, Jerônimo Aparecido; Franchin, Marcelo; Cavallini, Miriam Elias; Denny, Carina; de Alencar, Severino Matias; Ikegaki, Masaharu; Rosalen, Pedro Luiz

    2015-01-01

    The aim of this study was to evaluate the gastroprotective activity of ethanolic extract of geopropolis (EEGP) from Melipona scutellaris and to investigate the possible mechanisms of action. The gastroprotective activity of the EEGP was evaluated using model ulcer induced by ethanol. To elucidate the possible mechanisms of action, we investigated the involvement of the nonprotein sulfhydryl (NP-SH) groups, nitric oxide and prostaglandins. In addition, the antisecretory activity of EEGP was also evaluated by pylorus ligated model. The EEGP orally administrated (300 mg/kg) reduced the ulcerative lesions induced by the ethanol (P < 0.05). Regarding the mechanism of action, the prior administration of nitric oxide and prostaglandins antagonists suppressed the activity of gastroprotective EEGP (P < 0.05). On the other hand the gastroprotective activity of EEGP was kept in the group pretreated with the antagonist of the NP-SH groups; furthermore the antisecretory activity was not significant (P > 0.05). These results support the alternative medicine use of geopropolis as gastroprotective and the activities observed show to be related to nitric oxide and prostaglandins production. PMID:25949263

  20. Effect of radioprotectant WR 2721 on cyclic nucleotides, prostaglandins, and lysosomes

    SciTech Connect

    Trocha, P.J.; Catravas, G.N.

    1983-05-01

    Within 1 hr after ip injection of the radioprotectant WR 2721 into rats, splenic cGMP levels dropped and remained suppressed for 6 hr before returning to normal. However, if rats were exposed to ionizing radiation 30-40 min after WR 2721 treatment, they had higher cGMP levels at 3 hr postirradiation than the nonirradiUted, drug-treated controls, but the cGMP content was still found to be lower than that of the irradiated nondrug-treated controls. Radiation exposure of animals pretreated with WR 2721 also resulted in higher liver and spleen levels of cAMP and additional elevations in spleen prostaglandin content, compared with irradiated controls at 3-6 hr after radiation treatment. The secondary fluctuations of lysosomal enzyme activities, prostaglandin content, and cyclic nucleotide levels were also altered in irradiated rats pretreated with WR 2721 when compared with irradiated controls. Liver and spleen lysosomal ..beta..-glucuronidase activities, spleen cAMP and cGMP levels, and spleen prostaglandin concentrations were closer to physiological levels at 3 days postirradiation in rats given WR 2721 before the radiation treatment.

  1. Muscle sympathetic nerve responses to physiological changes in prostaglandin production in humans

    NASA Technical Reports Server (NTRS)

    Doerzbacher, K. J.; Ray, C. A.

    2001-01-01

    Previous studies suggest that prostaglandins may contribute to exercise-induced increases in muscle sympathetic nerve activity (MSNA). To test this hypothesis, MSNA was measured at rest and during exercise before and after oral administration of ketoprofen, a cyclooxygenase inhibitor, or placebo. Twenty-one subjects completed two bouts of graded dynamic and isometric handgrip to fatigue. Each exercise bout was followed by 2 min of postexercise muscle ischemia. The second exercise bouts were performed after 60 min of rest in which 11 subjects were given ketoprofen (300 mg) and 10 subjects received a placebo. Ketoprofen significantly lowered plasma thromboxane B(2) in the drug group (from 36 +/- 6 to 22 +/- 3 pg/ml, P < 0.04), whereas thromboxane B(2) in the placebo group increased from 40 +/- 5 to 61 +/- 9 pg/ml from trial 1 to trial 2 (P < 0.008). Ketoprofen and placebo did not change sympathetic and cardiovascular responses to dynamic handgrip, isometric handgrip, and postexercise muscle ischemia. There was no relationship between thromboxane B(2) concentrations and MSNA or arterial pressure responses during both exercise modes. The data indicate that physiological increases or decreases in prostaglandins do not alter exercise-induced increases in MSNA and arterial pressure in humans. These findings suggest that contraction-induced metabolites other than prostaglandins mediate MSNA responses to exercise in humans.

  2. Interactions between ADH and prostaglandins in isolated erythrocyte-perfused rat kidney

    SciTech Connect

    Lieberthal, W.; Vasilevsky, M.L.; Valeri, C.R.; Levinsky, N.G.

    1987-02-01

    Interactions between antidiuretic hormone (ADH) and renal prostaglandins in the regulation of sodium reabsorption and urinary concentrating ability were studied in isolated erythrocyte-perfused rat kidneys (IEPK). In this model, hemodynamic characteristics are comparable to those found in vivo, and tubular morphology is preserved throughout the period of perfusion. (Deamino)-D-arginine vasopressin (dDAVP) markedly reduced fractional sodium excretion (FE/sub Na/) in the IEPK. After indomethacin, FE/sub Na/ fell still further. In the absence of dDAVP indomethacin had no effect on sodium excretion. dDAVP increased urine osmolality in the IEPK. When prostaglandin synthesis was blocked with indomethacin, urinary osmolality increased further. In isolated kidneys perfused without erythrocytes (IPK), dDAVP decreased FE/sub Na/ from 14.5 +/- 1.8% to 9.6 +/- 1.2%. dDAVP increased urine osmolality only modestly in the IPK and indomethacin did not increase concentrating ability further. Thus the IEPK (unlike the IPK) can excrete markedly hypertonic urine in response to ADH. ADH also enhances tubular reabsorption of sodium in the IEPK. Prostaglandins inhibit both these actions of ADH but do not directly affect sodium excretion in the absence of the hormone. Prostaglandius were measured by radioimmunoassay.

  3. The flavouring phytochemical 2-pentanone reduces prostaglandin production and COX-2 expression in colon cancer cells.

    PubMed

    Pettersson, Jenny; Karlsson, Pernilla Christina; Göransson, Ulf; Rafter, Joseph James; Bohlin, Lars

    2008-03-01

    Many phytochemicals found in the diet may prevent colon carcinogenesis by affecting biochemical processes in the colonic mucosa. Inflammation and subsequent elevation of the enzyme cyclooxygenase-2 (COX-2) are two such factors involved in the development of colon cancer, and inhibition of these processes could be important targets for chemoprevention. We have previously shown COX-2 inhibitory activity locally in the colon; e.g. in human fecal water from a group of vegetarians. In this study we focus on 2-pentanone, a frequently occurring compound in common foods such as banana and carrot. The aim was to study the inhibitory effects on prostaglandin production and COX-2 protein expression in tumour necrosis factor-alpha stimulated colon cancer cells (HT29) by radioimmunoassay and Western blotting. 2-Pentanone inhibited both prostaglandin production and COX-2 protein expression in human colon cancer cells. A concentration of 400 mumol/l 2-pentanone inhibited the prostaglandin production by 56.9+/-12.9% which is in the same range as the reference compound NS398 (59.8+/-7.6%). The two highest concentrations of 2-pentanone were further analyzed by Western blot, and 400 micromol/l and 200 micromol/l 2-pentanone resulted in a 53.3+/-9.6% and +/-27.1% reduction of the COX-2 protein levels respectively. Further studies on flavouring compounds, for example 2-pentanone, as colon cancer chemopreventives would be very valuable, and such results may contribute to future dietary recommendations.

  4. Chronic stimulation of uterine prostaglandin synthesis during cervical ripening before the onset of labor.

    PubMed

    Keirse, M J; Thiery, M; Parewijck, W; Mitchell, M D

    1983-05-01

    Concentrations of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured in plasma of six carefully selected primigravid women with an unripe cervix at term before and at various intervals after extra-amniotic insertion of a Foley catheter with or without methylhydroxyethylcellulose (Tylose) gel. The procedure caused an acute elevation of PGFM levels within 5 min (P less than 0.025), which was maintained for at least 6 hours in the absence of uterine activation at 179 +/- 32% of the initial values (P less than 0.01). Extra-amniotic administration of Tylose gel caused an increase in PGFM levels which was both higher and more prolonged (greater than 12 hours) than insertion of a Foley catheter alone. The observations indicate that cervical ripening without concomitant uterine activation is associated with an increase in PGFM levels. They also demonstrate that prolonged activation of (intra) uterine prostaglandin synthesis may occur several hours before the onset of labor-like uterine activity. A chance finding further suggests that spontaneous rupture of the membranes too may be preceeded by an increase in (intra) uterine prostaglandin synthesis. In their totality these observations lend strong support to the proposition that an increase in (intra) uterine prostaglandin production is a prerequisite to rather than a consequence of the initiation of labor.

  5. Impact of prostaglandin glaucoma drops on platelet-activating factor action: an in vitro study

    PubMed Central

    Moschos, Marilita M; Nitoda, Eirini; Chatziralli, Irini P; Panos, Georgios D; Demopoulos, Constantinos A

    2016-01-01

    Aim The aim of this study was to investigate the effect of different prostaglandin analogs on platelet-activating factor (PAF) levels. Methods Three prostaglandin analogs were selected: bimatoprost 0.3 mg/mL, latanoprost 50 μg/mL, and tafluprost 15 μg/mL. Each drug sample was tested for its ability to cause platelet aggregation, which was measured as PAF-induced aggregation, before and after the addition of various concentrations of the examined sample, creating a linear curve of percentage inhibition (ranging from 0% to 100%) versus different concentrations of the sample. The concentration of the sample that inhibited 50% PAF-induced aggregation was calculated based on this curve, and this value was defined as IC50. In addition, the effect of eye drops on PAF metabolism was examined, through an in vitro analysis on PAF basic metabolic enzymes (PAF-cholinephosphotransferase, PAF-acetyl-CoA:1-O-alkyl-sn-glycero-3-phosphocholine acetyltransferase, and PAF-acetylhydrolase). Results The IC50 values for Lumigan UD® (bimatoprost 0.3 mg/mL), Monoprost® (latanoprost 50 μg/mL), and Saflutan (tafluprost 15 μg/mL) were 8.7, 0.28, and 1.4 μg/mL, respectively. Discussion All three prostaglandin analogs suspended PAF, but bimatoprost induced the most potent inhibition, compared to tafluprost and to the weak effect of latanoprost. PMID:27994439

  6. Inhibition of ADH-stimulated water flow by stable prostaglandin endoperoxide analogues.

    PubMed

    Ludens, J H; Taylor, C J

    1982-02-01

    The synthetic prostaglandin endoperoxide analogues 15-hydroxy-9,11-(epoxymethano)prosta-5,13-dien-1-oic acid (EPA-I) and 15-hydroxy-11,9-(epoxymethano)prosta-5,13-dien-1-oic acid (EPA-II) inhibited ADH-induced water flow in the isolated urinary bladder of the toad. In certain other biologic systems, EPA-I appeared to possess "thromboxane-like" activity. Thromboxanes, therefore, as well as the classical E prostaglandins may be modulators of the ADH response. To further characterize the effect of EPA-I on ADH, interaction studies were conducted with a related endoperoxide analogue found to be devoid of anti-ADH activity, 9,11-(epoxymethano)prostan-1-oic acid (EPA-III), and a prostanoid found to be a PGE antagonist in isolated toad bladder, 7-oxa-13-prostynoic acid. EPA-III reversed the anti-ADH activity of EPA-I but not that of PGE2. In contrast, 7-oxa-13-prostynoic acid reversed the anti-ADH activity of PGE2 but not that of an equieffective concentration of EPA-I. These findings suggest that the anti-ADH activity of EPA-I, and by inference thromboxane A2, may be mediated via a different receptor and/or pathway than that of the E prostaglandins.

  7. Effect of peroxisome proliferator activated receptor (PPAR)gamma agonists on prostaglandins cascade in joint cells.

    PubMed

    Moulin, David; Poleni, Paul-Emile; Kirchmeyer, Mélanie; Sebillaud, Sylvie; Koufany, Meriem; Netter, Patrick; Terlain, Bernard; Bianchi, Arnaud; Jouzeau, Jean-Yves

    2006-01-01

    In response to inflammatory cytokines, chondrocytes and synovial fibroblasts produce high amounts of prostaglandins (PG) which self-perpetuate locally the inflammatory reaction. Prostaglandins act primarily through membrane receptors coupled to G proteins but also bind to nuclear Peroxisome Proliferator-Activated Receptors (PPARs). Amongst fatty acids, the cyclopentenone metabolite of PGD2, 15-deoxy-Delta12,14PGJ2 (15d-PGJ2), was shown to be a potent ligand of the PPARgamma isotype prone to inhibit the production of inflammatory mediators. As the stimulated synthesis of PGE2 originates from the preferential coupling of inducible enzymes, cyclooxygenase-2 (COX-2) and membrane PGE synthase-1 (mPGES-1), we investigated the potency of 15d-PGJ2 to regulate prostaglandins synthesis in rat chondrocytes stimulated with interleukin-1beta (IL-1beta). We demonstrated that 15d-PGJ2, but not the high-affinity PPARgamma ligand rosiglitazone, decreased almost completely PGE2 synthesis and mPGES-1 expression. The inhibitory potency of 15d-PGJ2 was unaffected by changes in PPARgamma expression and resulted from inhibition of NF-kappaB nuclear binding and IkappaBalpha sparing, secondary to reduced phosphorylation of IKKbeta. Consistently with 15d-PGJ2 being a putative endogenous regulator of the inflammatory reaction if synthesized in sufficient amounts, the present data confirm the variable PPARgamma-dependency of its effects in joint cells while underlining possible species and cell types specificities.

  8. Prospects for Lentiviral Vector Mediated Prostaglandin F Synthase Gene Delivery in Monkey Eyes In vivo

    PubMed Central

    Lee, Eun Suk; Rasmussen, Carol A.; Filla, Mark S.; Slauson, Sarah R.; Kolb, Aaron W.; Peters, Donna M.; Kaufman, Paul L.; Gabelt, B’Ann True; Brandt, Curtis R.

    2014-01-01

    Currently, the most effective outflow drugs approved for clinical use are prostaglandin F2α analogues, but these require daily topical self-dosing and have various intraocular, ocular surface and extraocular side effects. Lentiviral vector-mediated delivery of the prostaglandin F synthase (PGFS) gene, resulting in long-term reduction of IOP, may eliminate off-target tissue effects and the need for daily topical PGF2α self-administration. Lentiviral vector-mediated delivery of the PGFS gene to the anterior segment has been achieved in cats and non-human primates. Although these results are encouraging, our studies have identified a number of challenges that need to be overcome for prostaglandin gene therapy to be translated into the clinic. Using examples from our work in non-human primates, where we were able to achieve a significant reduction in IOP (2 mm Hg) for 5 months after delivery of the cDNA for bovine PGF synthase, we identify and discuss these issues and consider several possible solutions. PMID:24559478

  9. Antifibrotic effects of noscapine through activation of prostaglandin E2 receptors and protein kinase A.

    PubMed

    Kach, Jacob; Sandbo, Nathan; La, Jennifer; Denner, Darcy; Reed, Eleanor B; Akimova, Olga; Koltsova, Svetlana; Orlov, Sergei N; Dulin, Nickolai O

    2014-03-14

    Myofibroblast differentiation is a key process in the pathogenesis of fibrotic disease. We have shown previously that differentiation of myofibroblasts is regulated by microtubule polymerization state. In this work, we examined the potential antifibrotic effects of the antitussive drug, noscapine, recently found to bind microtubules and affect microtubule dynamics. Noscapine inhibited TGF-β-induced differentiation of cultured human lung fibroblasts (HLFs). Therapeutic noscapine treatment resulted in a significant attenuation of pulmonary fibrosis in the bleomycin model of the disease. Noscapine did not affect gross microtubule content in HLFs, but inhibited TGF-β-induced stress fiber formation and activation of serum response factor without affecting Smad signaling. Furthermore, noscapine stimulated a rapid and profound activation of protein kinase A (PKA), which mediated the antifibrotic effect of noscapine in HLFs, as assessed with the PKA inhibitor, PKI. In contrast, noscapine did not activate PKA in human bronchial or alveolar epithelial cells. Finally, activation of PKA and the antifibrotic effect of noscapine in HLFs were blocked by the EP2 prostaglandin E2 receptor antagonist, PF-04418948, but not by the antagonists of EP4, prostaglandin D2, or prostacyclin receptors. Together, we demonstrate for the first time the antifibrotic effect of noscapine in vitro and in vivo, and we describe a novel mechanism of noscapine action through EP2 prostaglandin E2 receptor-mediated activation of PKA in pulmonary fibroblasts.

  10. Shared bimanual tasks elicit bimanual reflexes during movement.

    PubMed

    Mutha, Pratik K; Sainburg, Robert L

    2009-12-01

    Previous research has suggested distinct predictive and reactive control mechanisms for bimanual movements compared with unimanual motion. Recent studies have extended these findings by demonstrating that movement corrections during bimanual movements might differ depending on whether or not the task is shared between the arms. We hypothesized that corrective responses during shared bimanual tasks recruit bilateral rapid feedback mechanisms such as reflexes. We tested this hypothesis by perturbing one arm as subjects performed uni- and bimanual movements. Movements were made in a virtual-reality environment in which hand position was displayed as a cursor on a screen. During bimanual motion, we provided cursor feedback either independently for each arm (independent-cursor) or such that one cursor was placed at the average location between the arms (shared-cursor). On random trials, we applied a 40 N force pulse to the right arm 100 ms after movement onset. Our results show that while reflex responses were rapidly elicited in the perturbed arm, electromyographic activity remained close to baseline levels in the unperturbed arm during the independent-cursor trials. In contrast, when the cursor was shared between the arms, reflex responses were reduced in the perturbed arm and were rapidly elicited in the unperturbed arm. Our results thus suggest that when both arms contribute to achieving the task goal, reflex responses are bilaterally elicited in response to unilateral perturbations. These results agree with and extend recent suggestions that bimanual feedback control might be modified depending on task context.

  11. Elicited versus emitted behavior: Time to abandon the distinction.

    PubMed

    Domjan, Michael

    2016-03-01

    The concept of emitted behavior was formulated as a part of the original argument for the validity of a new kind of learning called operant conditioning. The rationale for operant conditioning contrasted it with Pavlovian or classical conditioning, which was (and remains) fundamentally based on responses to conditioned and unconditioned stimuli. Classical conditioned responses were said to be elicited. In contrast, operant behavior was viewed as emitted and controlled primarily by response consequences rather than antecedents. I argue that the distinction between emitted and elicited behavior is no longer warranted for three major reasons. First, the distinction was based on a view of Pavlovian conditioning that is no longer viable. Second, the distinction is incompatible with both empirical data and contemporary conceptualizations of operant behavior. Third, the only way to overcome these problems is to define emitted and elicited in terms of the type of conditioning (operant and classical) that produces these behaviors, but that approach makes the definitions circular and does not avoid implications of the terms that are misleading and counterproductive in light of contemporary research and thinking.

  12. Conditioned cues for smoking elicit preparatory responses in healthy smokers

    PubMed Central

    Winkler, Markus H.; Weyers, Peter; Mucha, Ronald F.; Stippekohl, Bastian; Stark, Rudolf

    2010-01-01

    Rationale Smoking cues are theorized to be conditioned stimuli (CSs) formed by repeated pairing with drug. Smoking paraphernalia can elicit subjective and physiological responses in smokers, indicative of positive affect and motivation to consume. Although these responses are probably the result of conditioning, direct evidence from human conditioning studies with physiological measures of motivational valence is rare. Objective The present study investigated the motivational properties of experimentally conditioned cues for smoking. Methods Thirty-nine smokers completed a differential conditioning protocol. Abstract pictures were used as CSs and single puffs on a cigarette as unconditioned stimulus (US). Skin conductance responses and facial electromyography of the zygomatic, corrugator, and orbicularis oris muscles were measured during conditioning. Results The conditioned cue for smoking (CS+) elicited stronger skin conductance responses and more activity of the zygomatic and orbicularis oris muscles than the CS−. Conclusions These results support the notion that through pairing with smoking, neutral stimuli acquire the ability to elicit preparatory physiological responses, which are assumed to play an important role in the maintenance of addiction and relapse in the natural environment. PMID:20953588

  13. Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons

    PubMed Central

    Iha, Higor A.; Kunisawa, Naofumi; Shimizu, Saki; Tokudome, Kentaro; Mukai, Takahiro; Kinboshi, Masato; Ikeda, Akio; Ito, Hidefumi; Serikawa, Tadao; Ohno, Yukihiro

    2017-01-01

    Nicotinic acetylcholine (nACh) receptors are implicated in the pathogenesis of epileptic disorders; however, the mechanisms of nACh receptors in seizure generation remain unknown. Here, we performed behavioral and immunohistochemical studies in mice and rats to clarify the mechanisms underlying nicotine-induced seizures. Treatment of animals with nicotine (1–4 mg/kg, i.p.) produced motor excitement in a dose-dependent manner and elicited convulsive seizures at 3 and 4 mg/kg. The nicotine-induced seizures were abolished by a subtype non-selective nACh antagonist, mecamylamine (MEC). An α7 nACh antagonist, methyllycaconitine, also significantly inhibited nicotine-induced seizures whereas an α4β2 nACh antagonist, dihydro-β-erythroidine, affected only weakly. Topographical analysis of Fos protein expression, a biological marker of neural excitation, revealed that a convulsive dose (4 mg/kg) of nicotine region-specifically activated neurons in the piriform cortex, amygdala, medial habenula, paratenial thalamus, anterior hypothalamus and solitary nucleus among 48 brain regions examined, and this was also suppressed by MEC. In addition, electric lesioning of the amygdala, but not the piriform cortex, medial habenula and thalamus, specifically inhibited nicotine-induced seizures. Furthermore, microinjection of nicotine (100 and 300 μg/side) into the amygdala elicited convulsive seizures in a dose-related manner. The present results suggest that nicotine elicits convulsive seizures by activating amygdalar neurons mainly via α7 nACh receptors. PMID:28232801

  14. Elicitation of andrographolide in the suspension cultures of Andrographis paniculata.

    PubMed

    Gandi, Suryakala; Rao, Kiranmayee; Chodisetti, Bhuvaneswari; Giri, Archana

    2012-12-01

    Andrographis paniculata belonging to the family Acanthaceae produces a group of diterpene lactones, one of which is the pharmaceutically important-andrographolide. It is known to possess various important biological properties like anticancer, anti-HIV, anti-inflammatory, etc. This is the first report on the production of andrographolide in the cell suspension cultures of Andrographis paniculata by 'elicitation'. Elicitation was attempted to enhance the andrographolide content in the suspension cultures of Andrographis paniculata and also to ascertain its stimulation under stress conditions or in response to pathogen attack. The maximum andrographolide production was found to be 1.53 mg/g dry cell weight (DCW) at the end of stationary phase during the growth curve. The biotic elicitors (yeast, Escherichia coli, Bacillus subtilis, Agrobacterium rhizogenes 532 and Agrobacterium tumefaciens C 58) were more effective in eliciting the response when compared to the abiotic elicitors (CdCl(2), AgNO(3), CuCl(2) and HgCl(2)). Yeast has shown to stimulate maximum accumulation of 13.5 mg/g DCW andrographolide, which was found to be 8.82-fold higher than the untreated cultures.

  15. Physiological responses induced by emotion-eliciting films.

    PubMed

    Fernández, Cristina; Pascual, Juan C; Soler, Joaquim; Elices, Matilde; Portella, Maria J; Fernández-Abascal, Enrique

    2012-06-01

    Emotion-eliciting films are commonly used to evoke subjective emotional responses in experimental settings. The main aim of the present study was to investigate whether a set of film clips with discrete emotions were capable to elicit measurable objective physiological responses. The convergence between subjective and objective measures was evaluated. Finally, the effect of gender on emotional responses was investigated. A sample of 123 subjects participated in the study. Individuals were asked to view a set of emotional film clips capable to induce seven emotions: anger, fear, sadness, disgust, amusement, tenderness and neutral state. Skin conductance level (SCL), heart rate (HR) and subjective emotional responses were measured for each film clip. In comparison with neutral films, SCL was significantly increased after viewing fear films, and HR was also significantly incremented for anger and fear films. Physiological variations were associated with arousal measures indicating a convergence between subjective and objective reactions. Women appeared to display significantly greater SCL and HR responses for films inducing sadness. The findings suggest that physiological activation would be more easily induced by emotion-eliciting films that tap into emotions with higher subjective arousal such as anger and fear.

  16. Elicitation of macrophages from the peritoneal cavity of channel catfish

    USGS Publications Warehouse

    Jenkins, J.A.; Klesius, P.H.

    1998-01-01

    Four chemicals were evaluated for elicitation of macrophages in peritoneal cavities of 250-300g healthy channel catfish Ictalurus punctatus. Cellular exudates were collected at 3, 5, 7, 10, 14, and 20 d following intraperitoneal injections with squalene, Freund's incomplete adjuvant (FIA), goat serum, thioglycollate, or as a control, phosphate-buffered saline. Injection with either squalene or FIA induced significantly greater (P ??? 0.0001) macrophage recruitment than the other chemicals. The effectiveness of squalene and FIA was compared further by macrophage collection daily for 7 d. Squalene and FIA elicited similarly high macrophage responses (P ??? 0.0450), the highest being 3.43 x 106 macrophages/mL (SE, 2.4 x l06) at 99% purity at day 2 and 2.1 X 106 macrophages/mL (SE, 0.7 x 106) at day 14 at 80% purity, respectively. In both experiments, the time after injection was not statistically significant, nor was there an interaction between time and chemicals. The occurrence of cells other than macrophages decreased with time to yield macrophage recoveries of 47-99% for squalene and 30-80% for FIA. Two subsets of macrophages were observed by means of flow cytometry. As demonstrated by chemiluminescence, the squalene-elicited cells produced high-energy oxygen compounds important to the phagocytic process.

  17. Reduction of urate crystal-induced inflammation by root extracts from traditional oriental medicinal plants: elevation of prostaglandin D2 levels

    PubMed Central

    Jung, Sung Mun; Schumacher, H Ralph; Kim, Hocheol; Kim, Miyeon; Lee, Seoung Hoon; Pessler, Frank

    2007-01-01

    Dried roots of the plants Acanthopanax senticosus, Angelica sinensis and Scutellaria baicalensis are used in traditional oriental medicine and reportedly possess anti-inflammatory properties. Using the murine air pouch model of inflammation, we investigated the efficacy and mode of action of an extract from these three plants in crystal-induced inflammation. Air pouches were raised on the backs of 8-week-old BALB/c mice. Mice were fed 100 mg/kg body weight of root extracts (A. senticosus:A. sinensis:S. baicalensis mixed in a ratio of 5:4:1 by weight) or vehicle only on days 3–6. Inflammation was elicited on day 6 by injecting 2 mg of monosodium urate (MSU) crystals into the pouch. Neutrophil density and IL-6 and TNF-α mRNA levels were determined in the pouch membrane, and the leukocyte count and IL-6, prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2) levels were determined in the pouch exudate. Treatment with the root extracts led to a reduction in all inflammatory parameters: the leukocyte count in the pouch exudate decreased by 82%; the neutrophil density in the pouch membrane decreased by 68%; IL-6 and TNF-α mRNA levels in the pouch membrane decreased by 100%; the IL-6 concentration in the pouch fluid decreased by 50%; and the PGE2 concentration in the pouch fluid decreased by 69%. Remarkably, the concentration of the potentially anti-inflammatory PGD2 rose 5.2-fold in the pouch exudate (p < 0.005), which led to a normalization of the PGD2:PGE2 ratio. A 3.7-fold rise in hematopoietic PGD synthase (h-PGDS) mRNA paralleled this rise in PGD2 (p = 0.01). Thus, the root extracts diminished MSU crystal-induced inflammation by reducing neutrophil recruitment and expression of pro-inflammatory factors and increasing the level of the potentially anti-inflammatory PGD2. These results support a need for further studies of the efficacy of these extracts in the treatment of inflammatory arthropathies and suggest elevation of PGD2 levels as a novel mechanism for an anti

  18. Expression of the prostaglandin F synthase AKR1B1 and the prostaglandin transporter SLCO2A1 in human fetal membranes in relation to spontaneous term and preterm labor.

    PubMed

    Alzamil, Hana A; Pawade, Joya; Fortier, Michel A; Bernal, A López

    2014-01-01

    Human labor is a complex series of cellular and molecular events that occur at the materno-fetal and uterine levels. Many hypotheses have been proposed for the initiation of human labor, one hypothesis suggests that maturation of the fetus releases a signal in the amniotic fluid that will be transmitted to myometrium via the fetal membranes and initiate uterine contractions. There is strong evidence that prostaglandins (PGs) play a central role in initiation and progression of human labor. In this study we intended to investigate the expression of prostaglandin F synthase and the prostaglandin transporter in the human fetal membranes and to explore the relationship between cytokines and PGs in the mechanism of human labor. We used fetal membranes obtained before labor at term and after spontaneous labor at term or preterm to identify the changes in prostaglandin F synthase (AKR1B1) and human prostaglandin transporter (SLCO2A1) proteins in relation to parturition. Using fetal membranes explants we tested the effect of cytokines (interleukin-1 and tumor necrosis factor alpha) on PG production and the concomitant changes in cyclooxygenase-2 (PTGS2), AKR1B1 and SLCO2A1 expression. Expression of PTGS2 and AKR1B1 was upregulated in the fetal membranes in association with term labor while SLCO2A1 was downregulated with advancing gestation and during term labor. Before labor, IL-1 increased the expression of PTGS2, however during labor TNF upregulated PTGS2 and AKR1B1 proteins. The prostaglandin F synthase AKR1B1 is upregulated while prostaglandin transporter is downregulated during term labor. The amnion is more responsive than choriodecidua to stimulation with pro-inflammatory cytokines. The mechanisms of term and preterm labor are different.

  19. Expression of the prostaglandin F synthase AKR1B1 and the prostaglandin transporter SLCO2A1 in human fetal membranes in relation to spontaneous term and preterm labor

    PubMed Central

    Alzamil, Hana A.; Pawade, Joya; Fortier, Michel A.; Bernal, A. López

    2014-01-01

    Background: Human labor is a complex series of cellular and molecular events that occur at the materno-fetal and uterine levels. Many hypotheses have been proposed for the initiation of human labor, one hypothesis suggests that maturation of the fetus releases a signal in the amniotic fluid that will be transmitted to myometrium via the fetal membranes and initiate uterine contractions. There is strong evidence that prostaglandins (PGs) play a central role in initiation and progression of human labor. Objectives: In this study we intended to investigate the expression of prostaglandin F synthase and the prostaglandin transporter in the human fetal membranes and to explore the relationship between cytokines and PGs in the mechanism of human labor. Methods: We used fetal membranes obtained before labor at term and after spontaneous labor at term or preterm to identify the changes in prostaglandin F synthase (AKR1B1) and human prostaglandin transporter (SLCO2A1) proteins in relation to parturition. Using fetal membranes explants we tested the effect of cytokines (interleukin-1 and tumor necrosis factor alpha) on PG production and the concomitant changes in cyclooxygenase-2 (PTGS2), AKR1B1 and SLCO2A1 expression. Results: Expression of PTGS2 and AKR1B1 was upregulated in the fetal membranes in association with term labor while SLCO2A1 was downregulated with advancing gestation and during term labor. Before labor, IL-1 increased the expression of PTGS2, however during labor TNF upregulated PTGS2 and AKR1B1 proteins. Conclusions: The prostaglandin F synthase AKR1B1 is upregulated while prostaglandin transporter is downregulated during term labor. The amnion is more responsive than choriodecidua to stimulation with pro-inflammatory cytokines. The mechanisms of term and preterm labor are different. PMID:25126080

  20. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

    SciTech Connect

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun; Park, Yong Seek; Park, Cheung-Seog; Jin, Young-Ho

    2015-01-02

    Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin