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Mifepristone
Kinds of Mifepristone Selected AbstractsPRECLINICAL STUDY: Mifepristone and spironolactone differently alter cocaine intravenous self-administration and cocaine-induced locomotion in C57BL/6J miceADDICTION BIOLOGY, Issue 1 2010Jean-François Fiancette ABSTRACT Corticosterone, the main glucorticoid hormone in rodents, facilitates behavioral responses to cocaine. Corticosterone is proposed to modulate cocaine intravenous self-administration (SA) and cocaine-induced locomotion through distinct receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), respectively. However, this remains debatable. On one hand, modulation of both responses by the GR was tested in different experimental conditions, i.e. light versus dark nycthemeral phase and naïve versus cocaine-experienced animals. On the other hand, modulation of both responses by the MR was never tested directly but only inferred based on the ability of low plasma corticosterone levels (those for which corticosterone almost exclusively binds the MR) to compensate the effects of adrenalectomy. Our goal here was to test the involvement of the GR and the MR in cocaine-induced locomotor and reinforcing effects in the same experimental conditions. C57Bl/6J mice were trained for cocaine (1 mg/kg/infusion) intravenous SA over 40 SA sessions. The animals were then administered with mifepristone (30 mg/kg i.p.), a GR antagonist, or with spironolactone (20 mg/kg/i.p.), an MR antagonist, 2 hours before either cocaine intravenous SA or cocaine-induced locomotion. In a comparable nycthemeral period and in similarly cocaine-experienced animals, a blockade of the GR decreased cocaine-induced reinforcing effects but not cocaine-induced locomotion. A blockade of the MR decreased both cocaine-induced reinforcing (but to a much lesser extent than the GR blockade) and locomotor effects. Altogether, our results comforted the hypothesis that the GR modulates cocaine-related operant conditioning, while the MR would modulate cocaine-related unconditioned effects. The present data also reveal mifepristone as an interesting tool for manipulating the impact of corticosterone on cocaine-induced reinforcing effects in mice. [source] Dexamethasone inhibits lipopolysaccharide-induced hydrogen sulphide biosynthesis in intact cells and in an animal model of endotoxic shockJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Ling Li Abstract Dexamethasone (1 mg/kg, i.p.) administered either 1 hr before or 1 hr after E. coli lipopolysaccharide (LPS, 4 mg/kg, i.p.) in conscious rats inhibited the subsequent (4 hrs) rise in plasma cytokine (interleukin [IL]-1,, tumour necrosis factor [TNF]-,), nitrate/nitrite (NO×), soluble intercellular adhesion molecule-1 (sICAM-1) concentration and lung/liver myeloperoxidase activity indicative of an anti-inflammatory effect. Dexamethasone also reduced the LPS-evoked rise in plasma hydrogen sulphide (H2S) concentration, liver H2S synthesizing activity and expression of cystathionine , lyase (CSE) and inducible nitric oxide synthase (iNOS). Mifepristone (RU-486) inhibited these effects. Dexamethasone (1,10 ,M) reduced the LPS-evoked release of IL-1,, TNF-, and L-selectin, decreased expression of CSE and iNOS and diminished nuclear factor ,B (NF-,B)-DNA binding in isolated rat neutrophils. In contrast, NaHS (100 ,M) increased L-selectin release from rat neutrophils. Dexamethasone also reduced LPS-induced up-regulation of CSE in foetal liver cells. 6-amino-4-(4-phenoxyphenylethylamino) quinazoline (QNZ, 10 nM), a selective inhibitor of transcription via the NF-,B pathway, abolished LPS-induced up-regulation of CSE expression. We propose that inhibition of CSE expression and reduction in formation of the pro-inflammatory component of H2S activity contributes to the anti-inflammatory effect of dexamethasone in endotoxic shock. Whether H2S plays a part in the anti-inflammatory effect of this steroid in other forms of inflammation such as arthritis or asthma warrants further study. [source] Arachidonic acid and its metabolites are involved in the expression of neocortical spike-and-wave spindling episodes in DBA/2J miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2001A. Capasso This work was undertaken to study the effects of dexamethasone, indometacin and mifepristone plus dexamethasone on the neocortical spike-and-wave spindling episodes (S&W) in the electrocorticogram of DBA/2J mice. Our data indicate that both dexamethasone and indometacin (1, 10, 100 ,g kg,1, i.p.) reduced the S&W of DBA/2J mice. This effect appeared 30 min after drug administration and lasted for the duration of the recording period (240 min). Mifepristone, a glucocorticoid receptor antagonist (1, 10, 100 ,g kg,1, i.p.), injected 2 h before dexamethasone, totally blocked the steroid effect. These results indicate that both dexamethasone and indometacin significantly reduce the S&W of DBA/2J mice, suggesting a possible involvement of arachidonic acid and its metabolites in the development of brain excitability. [source] Effects of the Glucocorticoid Antagonist, Mifepristone, on the Consequences of Withdrawal From Long Term Alcohol ConsumptionALCOHOLISM, Issue 12 2008Catherine Jacquot Background:, Studies were carried out to test the hypothesis that administration of a glucocorticoid Type II receptor antagonist, mifepristone (RU38486), just prior to withdrawal from chronic alcohol treatment, would prevent the consequences of the alcohol consumption and withdrawal in mice. Materials and Methods:, The effects of administration of a single intraperitoneal dose of mifepristone were examined on alcohol withdrawal hyperexcitability. Memory deficits during the abstinence phase were measured using repeat exposure to the elevated plus maze, the object recognition test, and the odor habituation/discrimination test. Neurotoxicity in the hippocampus and prefrontal cortex was examined using NeuN staining. Results:, Mifepristone reduced, though did not prevent, the behavioral hyperexcitability seen in TO strain mice during the acute phase of alcohol withdrawal (4 hours to 8 hours after cessation of alcohol consumption) following chronic alcohol treatment via liquid diet. There were no alterations in anxiety-related behavior in these mice at 1 week into withdrawal, as measured using the elevated plus maze. However, changes in behavior during a second exposure to the elevated plus maze 1 week later were significantly reduced by the administration of mifepristone prior to withdrawal, indicating a reduction in the memory deficits caused by the chronic alcohol treatment and withdrawal. The object recognition test and the odor habituation and discrimination test were then used to measure memory deficits in more detail, at between 1 and 2 weeks after alcohol withdrawal in C57/BL10 strain mice given alcohol chronically via the drinking fluid. A single dose of mifepristone given at the time of alcohol withdrawal significantly reduced the memory deficits in both tests. NeuN staining showed no evidence of neuronal loss in either prefrontal cortex or hippocampus after withdrawal from chronic alcohol treatment. Conclusions:, The results suggest mifepristone may be of value in the treatment of alcoholics to reduce their cognitive deficits. [source] ORIGINAL ARTICLE: Mifepristone as an Anti-Implantation Contraceptive Drug: Roles in Regulation of Uterine Natural Killer Cells during Implantation PhaseAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009Hong-Xia Zhu Problem, To investigate the immunological mechanism of low-dose mifepristone acting as a contraceptive at the level of the endometrium. Method of study, Endometrial explants were cultured in vitro with or without mifepristone treatment for 24 hr. Some tissues were fixed and immunostained for CD56, while other tissues were dissociated and cells analysed by three colour flow cytometry for CD3, CD56 and CD16. Results and conclusion, Results showed a significant increase in the number of CD56+ natural killer (NK) cells and the percentages of CD3, CD56+ CD16, NK cell subset in the tissue treated with mifepristone, while the percentage of CD3, CD56+ CD16+ NK cell subset remained unaffected. It shows that low-dose mifepristone increases the number of CD56+ NK cells and the percentage of CD3, CD56+ CD16, NK subset in receptive endometrium and provides new insights into the immunological mechanism of low-dose mifepristone as an anti-implantation contraceptive drug. [source] Mifepristone (Ru486) Antagonizes Monocyte Chemotactic Protein-3 Down-Regulation at Early Mouse Pregnancy Revealing Immunomodulatory Events in Ru486 Induced AbortionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2004Jaya Nautiyal Problem:, The survival of an embryo bearing the paternal antigens within the immunocompetent environment of the maternal uterus renders ,pregnancy' to be a state of immunological paradox. The ratio of Th1/Th2 responses is crucial for pregnancy maintenance. Monocyte Chemotactic Protein-3 (MCP3) is a pro-inflammatory, CC chemokine and a Th1 effector which is capable of eliciting significant anti-tumoral immune responses. Method of study:, MCP3 expression was investigated in the murine uterine tissue at different days of initial pregnancy and the effect of RU 486 in immature and delayed implantation model studied using Western blotting and Immunocytochemical techniques. Results and conclusion:, Our results show very high uterine MCP3 expression during pre-implantation followed by a significant MCP3 down-regulation at peri-implantation and low levels of MCP3 during post-implantation period. At the peri-implantation stage, embryos exhibited lowered MCP3 expression when compared with the pre-implantation stage. Ru486, a progesterone antagonist when given in a competitive mode with progesterone resulted in a massive surge in MCP3 expression in both immature mice and delayed implantation models. We hypothesize that it is imperative for MCP3 expression to be down-regulated for the success of pregnancy. The cross-talk between Ru486 and amplified MCP3 expression may be one of the mechanisms by way of which RU486 performs its abortificient and anti tumor role. [source] Mifepristone and second trimester pregnancy termination for fetal abnormality in Western Australia: Worth the effortAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 1 2010Jan E. DICKINSON Objective:, To determine the impact on the process of second trimester medical termination for fetal abnormality following the introduction of adjunctive mifepristone in an Australian tertiary hospital. Methods:, All second trimester medical terminations for fetal abnormality between July 2006 and June 2009 were prospectively identified. Two temporal therapeutic cohorts were created: the first (1 July 2006 to 31 December 2007) using vaginal misoprostol alone and the second (1 January 2008 to 30 June 2009) using mifepristone priming prior to the administration of misoprostol. The primary outcome was to evaluate the impact of mifepristone priming upon the duration of pregnancy termination. Results:, During the study period, 388 women with prenatally recognised fetal anomalies between 14 and 24 weeks gestation underwent medical termination: 189 with misoprostol alone and 199 with mifepristone priming followed by misoprostol. There was no difference between the groups for maternal age, parity or prior caesarean delivery. The median abortion duration was 15.5 h (interquartile ranges (IQR) 11.2,22.7) in the misoprostol group and 8.6 h (IQR 5.6,13.8) in the mifepristone primed group (P < 0.001). In both the groups, nulliparity and advancing gestation were associated with a significant prolongation of the abortion interval. Duration of hospitalisation was significantly longer in the misoprostol alone group (31.5 h (27,48.9) vs 27.2 h (22,31.5), misoprostol vs mifepristone priming, respectively, P < 0.001). Conclusions:, The introduction of mifepristone priming prior to second trimester medical termination with misoprostol has resulted in a significant reduction in the duration of the termination procedure and length of inpatient stay. These observed benefits of mifepristone provide objective support for the decision to permit use of this medication in Australia. [source] Comparison of three single doses of mifepristone as emergency contraception: a randomised controlled trialAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2005Jie JIN Abstract Background:, This is an analysis of the Australian component of a large World Health Organization multicentre dose-finding study of mifepristone for emergency contraception and the first clinical study of this controversial drug in Australia. Aims:, To compare the effectiveness and side-effects of three single doses of mifepristone taken within 120 h after unprotected coitus as emergency contraception. Design:, Double-blind, randomised controlled trial. Subjects and methods:, One hundred fifty healthy women with regular menstrual cycles who requested emergency contraception. Participants were allocated randomly to one of the three doses (10, 50 and 600 mg). The primary outcome was confirmed pregnancy, and secondary outcome measures included side-effects and delay in the onset of the next menses. Results:, Pregnancy rates for mifepristone 10, 50 and 600 mg were 2.0, 2.1 and 2.1%, respectively, with no significant difference between groups. No major side-effects occurred, except an unpredictable delay in the onset of the next menses. Mifepristone 600 mg caused a significantly longer delay in the onset of the next menses than either the 10 or the 50 mg dose. Conclusion:, Lowering the dose of mifepristone from 600 to 10 mg did not significantly impair its effectiveness as an emergency contraceptive, and caused less delay in the onset of the next menses. Therefore, a dose as low as 10 mg may be preferable to 600 mg for emergency contraception. This is very much lower than the dose required to terminate a pregnancy. [source] PRECLINICAL STUDY: Mifepristone and spironolactone differently alter cocaine intravenous self-administration and cocaine-induced locomotion in C57BL/6J miceADDICTION BIOLOGY, Issue 1 2010Jean-François Fiancette ABSTRACT Corticosterone, the main glucorticoid hormone in rodents, facilitates behavioral responses to cocaine. Corticosterone is proposed to modulate cocaine intravenous self-administration (SA) and cocaine-induced locomotion through distinct receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), respectively. However, this remains debatable. On one hand, modulation of both responses by the GR was tested in different experimental conditions, i.e. light versus dark nycthemeral phase and naïve versus cocaine-experienced animals. On the other hand, modulation of both responses by the MR was never tested directly but only inferred based on the ability of low plasma corticosterone levels (those for which corticosterone almost exclusively binds the MR) to compensate the effects of adrenalectomy. Our goal here was to test the involvement of the GR and the MR in cocaine-induced locomotor and reinforcing effects in the same experimental conditions. C57Bl/6J mice were trained for cocaine (1 mg/kg/infusion) intravenous SA over 40 SA sessions. The animals were then administered with mifepristone (30 mg/kg i.p.), a GR antagonist, or with spironolactone (20 mg/kg/i.p.), an MR antagonist, 2 hours before either cocaine intravenous SA or cocaine-induced locomotion. In a comparable nycthemeral period and in similarly cocaine-experienced animals, a blockade of the GR decreased cocaine-induced reinforcing effects but not cocaine-induced locomotion. A blockade of the MR decreased both cocaine-induced reinforcing (but to a much lesser extent than the GR blockade) and locomotor effects. Altogether, our results comforted the hypothesis that the GR modulates cocaine-related operant conditioning, while the MR would modulate cocaine-related unconditioned effects. The present data also reveal mifepristone as an interesting tool for manipulating the impact of corticosterone on cocaine-induced reinforcing effects in mice. [source] Sonographic appearance of the uterine cavity following administration of mifepristone and misoprostol for termination of pregnancyJOURNAL OF CLINICAL ULTRASOUND, Issue 6 2006Ofer Markovitch MD Abstract Purpose. To describe the sonographic appearance of the uterine cavity in women after administration of mifepristone and misoprostol for termination of pregnancy. Methods. Thirty-six women treated with mifepristone 600 mg followed by misoprostol 400 ,g 2 days later for termination of pregnancy were the subjects of the study. Gestational age as calculated from the last menstrual period was ,49 days. Pretreatment sonographic parameters, including gestational sac size and crown,rump length, were measured. The sonographic appearance of the uterine cavity was recorded and documented 6 hours (T-1) and 14 days (T-2) after administration of misoprostol. Results. The mean menstrual age of the patients was 42 days (range 31,49 days). The mean gestational age according to crown,rump length was 43 days (range 40,48 days). Sonographic examination performed atT-1 revealed 23 patients (62.9%) with a well-defined echogenic mass located in the uterine cavity, 2 patients (5.5%) with an intrauterine sac containing a nonviable embryo, and 11 patients (30.5%) with an endometrium thickness of 7,14 mm with no evidence of intrauterine contents. Doppler flow signals were detected in 15 of the 23 patients (65.2%) with an echogenic intrauterine mass. Sonographic examination performed at T-2 revealed 19 patients (52.8%) with a persistent echogenic intrauterine mass; Doppler flow could be detected in 15 of these patients (78.9%). Dilatation and curettage was required in 2 patients (5.6%) due to failure of treatment; all others regained normal menses. Conclusions. An intrauterine echogenic mass with well-defined borders, with or without Doppler flow signals, can be detected 2 weeks after administration of mifepristone and misoprostol for termination of pregnancy. Because most of the women in our study regained normal menses without further surgical intervention, this finding could indicate remnants of trophoblastic tissue evacuated spontaneously from the uterine cavity. Therefore, dilatation and curettage should be avoided in these cases, unless clinical symptoms or signs necessitate surgical intervention. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound 34:278,282, 2006 [source] Inhibition of apoptosis by progesterone in cardiomyocytesAGING CELL, Issue 5 2010Stephen Morrissy Summary While gender-based differences in heart disease have raised the possibility that estrogen (ES) or progesterone (PG) may have cardioprotective effects, recent controversy regarding hormone replacement therapy has questioned the cardiac effects of these steroids. Using cardiomyocytes, we tested whether ES or PG has protective effects at the cellular level. We found that PG but not ES protects cardiomyocytes from apoptotic cell death induced by doxorubicin (Dox). PG inhibited apoptosis in a dose-dependent manner, by 12 ± 4.0% at 1 ,m and 60 ± 1.0% at 10 ,m. The anti-apoptotic effect of PG was also time dependent, causing 18 ± 5% or 62 + 2% decrease in caspase-3 activity within 1 h or 72 h of pretreatment. While PG causes nuclear translocation of its receptor within 20 min, the cytoprotective effect of PG was canceled by mifepristone (MF), a PG receptor antagonist. Analyses using Affymetrix high-density oligonucleotide array and RT-PCR found that PG induced Bcl-xL, metallothionine, NADPH quinone oxidoreductase 1, glutathione peroxidase-3, and four isoforms of glutathione S-transferase. Western blot analyses revealed that PG indeed induced an elevation of Bcl-xL protein in a dose- and time-dependent manner. Nuclear run-on assay indicated that PG induced Bcl-xL gene transcription. Inhibiting the expression of Bcl-xL using siRNA reduced the cytoprotective effect of PG. Our data suggests that PG induces a cytoprotective effect in cardiomyocytes in association with induction of Bcl-xL gene. [source] Effect of Chronic Stress and Mifepristone Treatment on Voltage-Dependent Ca2+ Currents in Rat Hippocampal Dentate GyrusJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2006N. G. Van Gemert Chronic unpredictable stress affects many properties in rat brain. In the dentate gyrus, among other things, increased mRNA expression of the Ca2+ channel ,1C subunit has been found after 21 days of unpredictable stress in combination with acute corticosterone application (100 nM). In the present study, we examined: (i) whether these changes in expression are accompanied by altered Ca2+ currents in rat dentate granule cells recorded on day 22 and (ii) whether treatment with the glucocorticoid receptor antagonist mifepristone during the last 4 days of the stress protocol normalises the putative stress-induced effects. Three weeks of unpredictable stress did not affect Ca2+ current amplitude in dentate granule cells under basal conditions (i.e. after incubation with vehicle solution). However, the sustained Ca2+ current component (which largely depends on the ,1C subunit) was significantly increased in amplitude after chronic stress when slices had been treated with corticosterone 1,4 h before recording. These findings suggest that dentate granule cells are exposed to an increased calcium load after exposure to an acute stressor when they have a history of chronic stress, potentially leading to increased vulnerability of the cells. The present results are in line with the molecular data on Ca2+ channel ,1C subunit expression. A significant three-way interaction between chronic stress, corticosterone application and mifepristone treatment was found, indicating that the combined effect of stress and corticosterone depends on mifepristone cotreatment. Interestingly, current density (defined as total current divided by capacitance) did not differ between the groups. This indicates that the observed changes in Ca2+ current amplitude could be attributable to changes in cell size. [source] Brief Treatment With the Glucocorticoid Receptor Antagonist Mifepristone Normalises the Corticosterone-Induced Reduction of Adult Hippocampal NeurogenesisJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2006J. L. Mayer The glucocorticoid receptor antagonist mifepristone has been shown to rapidly and effectively ameliorate symptoms of psychotic major depression. To better understand its mechanism, we investigated mifepristone's cellular effects, and found that it rapidly reversed a chronic corticosterone-induced reduction of adult neurogenesis in rats. Unlike other antidepressants, mifepristone is particularly potent in a high corticosterone environment. These data indicate that similarly to its clinical efficacy, mifepristone's effects on adult neurogenesis are rapid and positive, and may therefore be important for its mechanism of action. [source] Arachidonic acid and its metabolites are involved in the expression of neocortical spike-and-wave spindling episodes in DBA/2J miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2001A. Capasso This work was undertaken to study the effects of dexamethasone, indometacin and mifepristone plus dexamethasone on the neocortical spike-and-wave spindling episodes (S&W) in the electrocorticogram of DBA/2J mice. Our data indicate that both dexamethasone and indometacin (1, 10, 100 ,g kg,1, i.p.) reduced the S&W of DBA/2J mice. This effect appeared 30 min after drug administration and lasted for the duration of the recording period (240 min). Mifepristone, a glucocorticoid receptor antagonist (1, 10, 100 ,g kg,1, i.p.), injected 2 h before dexamethasone, totally blocked the steroid effect. These results indicate that both dexamethasone and indometacin significantly reduce the S&W of DBA/2J mice, suggesting a possible involvement of arachidonic acid and its metabolites in the development of brain excitability. [source] Effects of the Glucocorticoid Antagonist, Mifepristone, on the Consequences of Withdrawal From Long Term Alcohol ConsumptionALCOHOLISM, Issue 12 2008Catherine Jacquot Background:, Studies were carried out to test the hypothesis that administration of a glucocorticoid Type II receptor antagonist, mifepristone (RU38486), just prior to withdrawal from chronic alcohol treatment, would prevent the consequences of the alcohol consumption and withdrawal in mice. Materials and Methods:, The effects of administration of a single intraperitoneal dose of mifepristone were examined on alcohol withdrawal hyperexcitability. Memory deficits during the abstinence phase were measured using repeat exposure to the elevated plus maze, the object recognition test, and the odor habituation/discrimination test. Neurotoxicity in the hippocampus and prefrontal cortex was examined using NeuN staining. Results:, Mifepristone reduced, though did not prevent, the behavioral hyperexcitability seen in TO strain mice during the acute phase of alcohol withdrawal (4 hours to 8 hours after cessation of alcohol consumption) following chronic alcohol treatment via liquid diet. There were no alterations in anxiety-related behavior in these mice at 1 week into withdrawal, as measured using the elevated plus maze. However, changes in behavior during a second exposure to the elevated plus maze 1 week later were significantly reduced by the administration of mifepristone prior to withdrawal, indicating a reduction in the memory deficits caused by the chronic alcohol treatment and withdrawal. The object recognition test and the odor habituation and discrimination test were then used to measure memory deficits in more detail, at between 1 and 2 weeks after alcohol withdrawal in C57/BL10 strain mice given alcohol chronically via the drinking fluid. A single dose of mifepristone given at the time of alcohol withdrawal significantly reduced the memory deficits in both tests. NeuN staining showed no evidence of neuronal loss in either prefrontal cortex or hippocampus after withdrawal from chronic alcohol treatment. Conclusions:, The results suggest mifepristone may be of value in the treatment of alcoholics to reduce their cognitive deficits. [source] ORIGINAL ARTICLE: Mifepristone as an Anti-Implantation Contraceptive Drug: Roles in Regulation of Uterine Natural Killer Cells during Implantation PhaseAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009Hong-Xia Zhu Problem, To investigate the immunological mechanism of low-dose mifepristone acting as a contraceptive at the level of the endometrium. Method of study, Endometrial explants were cultured in vitro with or without mifepristone treatment for 24 hr. Some tissues were fixed and immunostained for CD56, while other tissues were dissociated and cells analysed by three colour flow cytometry for CD3, CD56 and CD16. Results and conclusion, Results showed a significant increase in the number of CD56+ natural killer (NK) cells and the percentages of CD3, CD56+ CD16, NK cell subset in the tissue treated with mifepristone, while the percentage of CD3, CD56+ CD16+ NK cell subset remained unaffected. It shows that low-dose mifepristone increases the number of CD56+ NK cells and the percentage of CD3, CD56+ CD16, NK subset in receptive endometrium and provides new insights into the immunological mechanism of low-dose mifepristone as an anti-implantation contraceptive drug. [source] Mifepristone and second trimester pregnancy termination for fetal abnormality in Western Australia: Worth the effortAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 1 2010Jan E. DICKINSON Objective:, To determine the impact on the process of second trimester medical termination for fetal abnormality following the introduction of adjunctive mifepristone in an Australian tertiary hospital. Methods:, All second trimester medical terminations for fetal abnormality between July 2006 and June 2009 were prospectively identified. Two temporal therapeutic cohorts were created: the first (1 July 2006 to 31 December 2007) using vaginal misoprostol alone and the second (1 January 2008 to 30 June 2009) using mifepristone priming prior to the administration of misoprostol. The primary outcome was to evaluate the impact of mifepristone priming upon the duration of pregnancy termination. Results:, During the study period, 388 women with prenatally recognised fetal anomalies between 14 and 24 weeks gestation underwent medical termination: 189 with misoprostol alone and 199 with mifepristone priming followed by misoprostol. There was no difference between the groups for maternal age, parity or prior caesarean delivery. The median abortion duration was 15.5 h (interquartile ranges (IQR) 11.2,22.7) in the misoprostol group and 8.6 h (IQR 5.6,13.8) in the mifepristone primed group (P < 0.001). In both the groups, nulliparity and advancing gestation were associated with a significant prolongation of the abortion interval. Duration of hospitalisation was significantly longer in the misoprostol alone group (31.5 h (27,48.9) vs 27.2 h (22,31.5), misoprostol vs mifepristone priming, respectively, P < 0.001). Conclusions:, The introduction of mifepristone priming prior to second trimester medical termination with misoprostol has resulted in a significant reduction in the duration of the termination procedure and length of inpatient stay. These observed benefits of mifepristone provide objective support for the decision to permit use of this medication in Australia. [source] Re: Low-dose mifepristone: Effects on the endometrium.AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2009Aust N Z J Obstet Gynaecol 2009; 49: 7 No abstract is available for this article. [source] Choosing medical or surgical terminations of pregnancy in the first trimester: What is the difference?AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2009Felicity GOODYEAR-SMITH Background: Women seeking termination of pregnancy in Auckland, New Zealand can chose between medical and surgical options up to eight weeks gestation. Aims: To assess demographic differences or changes over time between proportions of women choosing medical or surgical abortions at a single centre and determine whether changing the mifepristone,misoprostol interval from two to one day impacted on outcomes. Methods: Retrospective audit of two consecutive years (December 2005,November 2006 and December 2006,November 2007) of first-trimester surgical and medical terminations where the mifepristone-misoprostol interval was reduced from two to one day between years. Analysis using descriptive statistics and assessment of probability of observed differences between groups. Results: A total of 1495 terminations were performed in 2005,2006 and 1588 in 2006,2007. No significant difference (P = 0.4) of eligible women choosing medical (21% and 23%) or surgical abortion between years. Ethnicity, age and residency status did not influence choice. Medical termination of pregnancy was more likely in women who were without previous children (P = 0.009), pregnancies (P = 0.02) or terminations (P = 0.04). Medical termination was similarly effective within six hours with either two- or one-day intervals. Conclusions: Both medical and surgical first-trimester abortions are safe and effective. It is optimal to be able to offer women choice. Reducing the medical interval to one day does not increase adverse outcomes. [source] Low-dose mifepristone in treatment of uterine leiomyoma: A randomised double-blind placebo-controlled clinical trialAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 1 2009Madhu BAGARIA Aims: To evaluate the effect of low-dose mifepristone on leiomyoma-related symptoms, uterine and leiomyoma in women with symptomatic leiomyomata. Methods: In a double-blind placebo-controlled trial, 40 patients with symptomatic leiomyoma and normal endometrial histology were randomised to receive 10 mg mifepristone (group 1) or placebo (group 2) daily for three months. Leiomyoma-related symptoms, uterine, leiomyoma and largest leiomyoma volumes were assessed at baseline and every month for three months. Endometrial biopsy was repeated at the end of therapy. Results: Significant change was noticed between the two groups for mean menstrual blood loss (MBL) by first month. Menstrual blood loss declined by 94.8% in group 1 at three months and 84.2% patients attained amenorrhoea in this group. In group 1 complete relief of dysmenorrhoea occurred in significant number of women (80%) but only 33% patients got rid of pelvic pain. There was no change in these symptoms in group 1 Backache, urinary complaints and dyspareunia were not relieved in either group. Uterine, leiomyoma and largest leiomyoma volume declined by 26,32% in group 1 as compared to none in group 2, and this difference was statistically significant only by the end of the third month of therapy. Mean haemoglobin increased from 9.5 to 11.2 g/dL in group 1. In group 1, at the end of therapy, 63.1% of patients had endometrial hyperplasia without atypia. Conclusions: Ten milligrams mifepristone for three months is effective in reducing MBL, increasing haemoglobin and reducing uterine and leiomyoma volume with side-effect of endometrial hyperplasia. [source] Comparison of three single doses of mifepristone as emergency contraception: a randomised controlled trialAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2005Jie JIN Abstract Background:, This is an analysis of the Australian component of a large World Health Organization multicentre dose-finding study of mifepristone for emergency contraception and the first clinical study of this controversial drug in Australia. Aims:, To compare the effectiveness and side-effects of three single doses of mifepristone taken within 120 h after unprotected coitus as emergency contraception. Design:, Double-blind, randomised controlled trial. Subjects and methods:, One hundred fifty healthy women with regular menstrual cycles who requested emergency contraception. Participants were allocated randomly to one of the three doses (10, 50 and 600 mg). The primary outcome was confirmed pregnancy, and secondary outcome measures included side-effects and delay in the onset of the next menses. Results:, Pregnancy rates for mifepristone 10, 50 and 600 mg were 2.0, 2.1 and 2.1%, respectively, with no significant difference between groups. No major side-effects occurred, except an unpredictable delay in the onset of the next menses. Mifepristone 600 mg caused a significantly longer delay in the onset of the next menses than either the 10 or the 50 mg dose. Conclusion:, Lowering the dose of mifepristone from 600 to 10 mg did not significantly impair its effectiveness as an emergency contraceptive, and caused less delay in the onset of the next menses. Therefore, a dose as low as 10 mg may be preferable to 600 mg for emergency contraception. This is very much lower than the dose required to terminate a pregnancy. [source] First trimester abortion with mifepristone and three doses of sublingual misoprostol: a pilot studyAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2005Kishor C. SINGH Abstract Objective:, To evaluate the efficacy and safety of a medical abortion regimen with multiple doses of sublingual misoprostol 24 h after mifepristone. Methods:, The regimen was designed on the basis of pharmacokinetics of various routes of administration of misoprostol. Forty women 8 weeks' gestation were given mifepristone 200 mg orally, followed 24 h later by three doses of misoprostol 200 µgm sublingually 6 h apart. They were followed up on day 3 and day 14 with transvaginal ultrasound. Pain and bleeding were assessed using a visual analogue scale and acceptability, by a questionnaire. Results:, Abortion outcome was assessed in terms of onset of pain and vaginal bleeding, time of expulsion of products and duration of vaginal bleeding. Seventy-five per cent of women experienced pain within 2 h after first dose of misoprostol. Bleeding began at a mean of 1.41 h after pain and expulsion at a mean of 6.1 h after first dose of misoprostol. Complete expulsion was confirmed in all women (100%) by ultrasound on day 14. The longest duration of bleeding was 12 days (mean 7.2 days) with 87.5% bleeding for < 10 days. Acceptability was 100% but 70% perceived pain to be moderate and 67.5% bleeding to be light or slightly more than menses. Conclusions:, Medical abortion using three doses of sublingual misoprostol administered 24 h after mifepristone appears to be the most appropriate in terms of pharmacokinetics of the drugs. This pilot study associates the regimen with a short abortion process, which appears to be safe, highly efficacious and acceptable. [source] Introduction of early medical abortion in New Zealand: An audit of the first 67 casesAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 4 2005Carol SHAND Abstract Background:, In New Zealand, mifepristone became available in 2001, but because of uncertainty about the law, the first 67 cases were carried out under a very strict protocol. Once the prostaglandin had been administered it was necessary that the woman remain in the unit until the products of conception (POC) had been passed and, if this had not occurred within 8 h, she underwent suction curettage. Aims:, To demonstrate that an early medical termination of pregnancy (EMTOP) service could be offered as a safe option for women, despite the constraints of the law. Methods:, An audit of patient notes was carried out on the first 67 patients undergoing an EMTOP at the Level J Unit (LJU), Wellington Hospital. Data collected included age, ethnicity, parity, previous abortions, gestational age, length of time between the administration of mifepristone and misoprostol, length of time after administration of misoprostol to the completion of abortion, whether a fetal sac was seen, analgesia required, extent of heavy bleeding and any adverse effects. Patient characteristics were compared with those of the 3052 women who underwent surgical termination during the same time period. Data were analysed using EpiInfo 2000 (Centers for Disease Control and Prevention, Atlanta, GA) and Chi square tests for significance. Results:, Successful completion of EMTOP occurred in 63 of 67 cases (94%). Only four cases (6%) required completion by suction curettage and this was performed for legal and financial reasons, rather than for medical reasons. Clinical events requiring management, mainly bleeding problems, occurred in 11 patients (16%). Conclusions:, EMTOP with mifepristone and misoprostol was successfully introduced and the experience provides useful data for others contemplating a similar service. [source] Simultaneous determination of mifepristone and monodemethyl-mifepristone in human plasma by liquid chromatography,tandem mass spectrometry method using levonorgestrel as an internal standard: application to a pharmacokinetic studyBIOMEDICAL CHROMATOGRAPHY, Issue 1 2009Cheng Tang Abstract A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine mifepristone and monodemethyl-mifepristone in human plasma using levonorgestrel as the internal standard (IS). After solid-phase extraction of the plasma samples, mifepristone, monodemethyl-mifepristone and the IS were subjected to LC-MS/MS analysis using electro-spray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Chromatographic separation was performed on an XTERRA MS C18 column (150 × 2.1 mm i.d., 5 µm). The method had a chromatographic run time of 4.5 min and linear calibration curves over the concentration ranges of 5,2000 ng/mL for mifepristone and monodemethyl-mifepristone. The recoveries of the method were found to be 94.5,103.7% for mifepristone and 70.7,77.3% for monodemethyl-mifepristone. The method had a lower limit of quantification (LLOQ) of 5.0 ng/mL and a lower limit of detection (LOD) of 1.0 ng/mL for both mifepristone and monodemethyl-mifepristone. The intra- and inter-batch precision was less than 15% for all quality control samples at concentrations of 10, 100 and 1000 ng/mL. These results indicate that the method was efficient with a short run time (4.5 min) and acceptable accuracy, precision and sensitivity. The validated LC-MS/MS method was successfully used in a pharmacokinetic study in healthy female volunteers after oral administration of 25 mg mifepristone tablet. Copyright © 2008 John Wiley & Sons, Ltd. [source] Sialylation enhancement of CTLA4-Ig fusion protein in Chinese hamster ovary cells by dexamethasoneBIOTECHNOLOGY & BIOENGINEERING, Issue 3 2010Ying Jing Abstract The importance of glycoprotein sialic acid levels is well known, as increased levels have been shown to increase in vivo serum half-life profiles. Here we demonstrate for the first time that dexamethasone (DEX) was capable of improving the sialylation of a CTLA4-Ig fusion protein produced by Chinese hamster ovary (CHO) cells. DEX was shown to enhance the intracellular addition of sialic acid by sialyltransferases as well as reduce extracellular removal of sialic acid by sialidase cleavage. We illustrated that DEX addition resulted in increased expression of the glycosyltransferases ,2,3-sialyltransferase (,2,3-ST) and ,1,4-galactosyltransferase (,1,4-GT) in CHO cells. Based upon our previous results showing DEX addition increased culture cell viability, we confirmed here that cultures treated with DEX also resulted in decreased sialidase activity. Addition of the glucocorticoid receptor (GR) antagonist mifepristone (RU-486) was capable of blocking the increase in sialylation by DEX which further supports that DEX affected sialylation as well as provides evidence that the sialylation enhancement effects of DEX on recombinant CHO cells occurred through the GR. Finally, the effects of DEX on increasing sialylation were then confirmed in 5-L controlled bioreactors. Addition of 1,µM DEX to the bioreactors on day 2 resulted in harvests with average increases of 16.2% for total sialic acid content and 15.8% in the protein fraction with N-linked sialylation. DEX was found to be a simple and effective method for increasing sialylation of this CTLA4-Ig fusion protein expressed in CHO cells. Biotechnol. Bioeng. 2010;107: 488,496. © 2010 Wiley Periodicals, Inc. [source] Using telemedicine for termination of pregnancy with mifepristone and misoprostol in settings where there is no access to safe servicesBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2008J Haldane No abstract is available for this article. [source] Author response to: Using telemedicine for termination of pregnancy with mifepristone and misoprostol in settings where there is no access to safe servicesBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2008R Gomperts No abstract is available for this article. [source] Randomised controlled trial comparing the efficacy of same-day administration of mifepristone and misoprostol for termination of pregnancy with the standard 36 to 48 hour protocolBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 2 2007J Guest Objective, To determine the efficacy of oral mifepristone followed by vaginal misoprostol 6 hours later compared with the standard 36- to 48-hour regimen for medical termination of pregnancy. Design, Single centre, two arm, parallel, open randomised controlled trial. Setting, Medical termination service at a teaching hospital. Sample, Four hundred and fifty women undergoing medical termination of pregnancy at up to 63 days of gestation. Methods, Eligible women were randomised to receive mifepristone 200 mg orally followed by vaginal misoprostol 800 micrograms either 6 hours (n= 225) or 36,48 hours (n= 225) later. All participants were invited to attend for a follow-up pelvic ultrasound scan within 7 days following the misoprostol administration. For those women in whom products of conception remained at the follow-up ultrasound scan, expectant management ensued with weekly follow-up ultrasound scans until the termination was complete. They could elect to undergo an evacuation of uterus at any stage following the scan. Those women with a nonviable gestation sac at the follow-up scan were offered a further dose of vaginal misoprostol 800 micrograms or suction termination of pregnancy. Women with a continuing pregnancy were managed with surgical termination. Main outcome measure, Successful medical abortion defined as no requirement for medical or surgical intervention beyond the initial dose of misoprostol. Results, One hundred and sixty-five women (79%) in the 6-hour group and 197 women (92%) in the 36- to 48-hour group had a successful termination at first follow-up ultrasound or presumed on the basis of other considerations (those not seen for ultrasound but deemed successful by negative pregnancy test, products passed on ward or long-term assessment of notes). Twenty-two women (10%) in the 6-hour regimen required up to three further ultrasound scans after 7 days following the mifepristone administration in order to ensure that the termination process was complete. None of these women required a suction evacuation of uterus. In the 36- to 48-hour regimen, ten (5%) women had up to two further ultrasound scans to confirm a complete termination without the need for a surgical evacuation of uterus. Therefore, the overall successful termination rate in the 6-hour regimen was 89% (187/210) compared with 96% (207/215) in the 36- to 48-hour regimen (relative risk = 0.92, 95% CI 0.84,0.98). Repeat administration of misoprostol or surgical treatment was required in 23 women (11%) in the 6-hour group and 8 women (4%) in the 36- to 48-hour group. A viable pregnancy was found in five women (2%) in the 6-hour group and in three women (1%) in the 36- to 48-hour group. Conclusions, Oral mifepristone 200 mg followed by vaginal misoprostol 800 micrograms after 6 hours is not as effective at achieving a complete abortion compared with the 36- to 48-hour protocol. [source] Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent miscarriageBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2005Raj Raghupathy Objective To examine the effects of dydrogesterone on the production of Th1 and Th2 cytokines by lymphocytes from women undergoing unexplained recurrent spontaneous miscarriage (RSM). Design Controlled prospective, clinical study conducted in a maternity hospital and a university-based immunology laboratory. Setting Faculty of Medicine, Kuwait University and Kuwait Maternity Hospital. Sample Thirty women with unexplained RSM. Methods Peripheral blood mononuclear cells (PBMC) from women with unexplained RSM were isolated from venous blood by density gradient sedimentation and stimulated with phytohaemagglutinin (PHA). Culture supernatants assayed for interferon (IFN)-,, tumour necrosis factor (TNF)-,, interleukin (IL)-4, IL-6 and IL-10 by ELISA. Levels of the progesterone-induced blocking factor (PIBF) were also measured. Main outcome measures Cytokine production in the presence and absence of progesterone and dydrogesterone. Results Dydrogesterone significantly inhibited the production of the Th1 cytokines IFN-, (P= 0.0001) and TNF-, (P= 0.005) and induced an increase in the levels of the Th2 cytokines IL-4 (P= 0.03) and IL-6 (P= 0.017) resulting in a substantial shift in the ratio of Th1/Th2 cytokines. The effect of dydrogesterone was blocked by the addition of the progesterone-receptor antagonist mifepristone, indicating that dydrogesterone was acting via the progesterone receptor. Dydrogesterone induced the production of PIBF. Conclusion Dydrogesterone inhibits the production of the Th1 cytokines IFN-, and TNF-, from lymphocytes and up-regulates the production of the Th2 cytokines IL-4 and IL-6, inducing a Th1 to Th2 cytokine shift. [source] Medical management of early fetal demise using sublingual misoprostolBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 4 2002Prabhath T. Wagaarachchi The aim of this study was to determine the efficacy of mifepristone in combination with sublingual misoprostol for the medical management of early fetal demise. Fifty-six consecutive women were studied prospectively. The mean (SD) gestation at diagnosis was 9.6 weeks (1.84). Four women had complete miscarriage with mifepristone alone. The overall success rate was 83.9% and the median induction,miscarriage interval was 8.19 hours (range 0.83 to 37.50 hours). Of those women who had a successful outcome, 91.5% were satisfied with the regimen. Sublingual misoprostol in combination with mifepristone is an effective and safe alternative to vaginal or oral misoprostol in the management of early fetal demise. [source] | |||||||||||||