Mifepristone

BackgroundCortisol plays a multifaceted role in major depression disorder (MDD). Diurnal rhythms are disturbed, there is increased resistance to the feedback action of glucocorticoids, excess cortisol may induce MDD, basal levels may be higher and the post-awakening cortisol surge accentuated in those at risk for MDD. Does this suggest new avenues for studying MDD or its clinical management?MethodThe relevant literature was reviewed.ResultsCortisol contributes to genetic variants for the risk for MDD and the way that environmental events amplify risk. The corticoids' influence begins prenatally, but continues into adulthood. The impact of cortisol at each phase depends not only on its interaction with other factors, such as psychological traits and genetic variants, but also on events that have, or have not, occurred previously.ConclusionsThis review suggests that the time is now right for serious consideration of the role of cortisol in a clinical context. Estimates of cortisol...

Here we describe the three-dimensional crystal structures of human glucocorticoid receptor ligand-binding domain (GR-LBD) in complex with the antagonist RU-486 at 2.3 A resolution and with the agonist dexamethasone ligand together with a coactivator peptide at 2.8 A. The ...

Early first-trimester medical abortion (MA) service (≤ 63 days) has been provided by doctors and nurses under doctors' supervision since 2009 in Nepal. This paper assesses whether MA services provided by specifically trained and certified nurses and auxiliary nurse-midwives independently from doctors' supervision, is considered as satisfactory by women as those provided by doctors. The data come from a multi-center, randomized, controlled equivalence trial conducted between April 2009 and March 2010 in five district hospitals in Nepal. Women seeking MA were randomly assigned to doctors or nurses and auxiliary nurse-midwives(ANMs).Eligible women were administered 200 mg mifepristone orally followed by 800 μg misoprostol vaginally two days later by their assigned providers and followed up 10-14 days later. At the follow-up visit women's reported satisfaction with MA service they received was measured. Of 1295 women screened for eligibility, 535 were randomly assigned to a ...

The present work investigated whether polyamines play a role in the control of the innate immune response in the brain. The first evidence that these molecules may be involved in such a process was based on the robust increase in the expression of the first and rate-limiting enzyme of biosynthesis of polyamines during immune stimuli. Indeed, systemic lipopolysaccharide (LPS) administration increased ornithine decarboxylase (ODC) mRNA and protein within neurons and microglia across the mouse central nervous system (CNS). This treatment was also associated with a robust and transient transcriptional activation of genes encoding pro-inflammatory cytokines and toll-like receptor 2 (TLR2) in microglial cells. The endotoxin increased the cerebral activity of ODC, which was abolished by a suicide inhibitor of ODC. The decrease in putrescine levels largely prevented the ability of LPS to trigger tumor necrosis factor α and TLR2 gene transcription in the mouse brain. In contrast, expression ...

Rationale: Mifepristone was approved in 2000 by the FDA as an alternative to surgical abortion. In the predominant two drug abortion regimen, mifepristone is followed by misoprostol after one to two days. Little has been published on the survival of living embryos after exposure to mifepristone alone. This review of the literature is undertaken to summarize available studies that define embryo survival after mifepristone. This review defines baseline continuing pregnancy rates after mifepristone, to aid in determining the therapeutic value of supplemental progesterone for women desiring to continue their pregnancy. Methods: PubMed and the Cochrane Database were searched through March, 2016 for articles that depicted embryo survival after ingestion of mifepristone as a single agent. Further studies were found in the reference lists of relevant articles and review articles. The relevant studies that verified embryo survival utilized ultrasound as a criterion for continuing pregnancy. ...

Hypercortisolemia, long-term exposure of the brain to high concentrations of stress hormones (i.e. cortisol), may occur in patients suffering from depression, alcoholism, and other disorders. This has been suggested to produce neuropathological effects, in part, via increased function or sensitivity of N-methyl-d-aspartate (NMDA)-type glutamate receptors. Given that cigarette smoking is highly prevalent in some of these patient groups and nicotine

A significant proportion of breast cancer patients face failure of endocrine therapy due to the acquisition of endocrine resistance. We have explored mechanisms involved in such disease progression by using a mouse breast cancer model that is induced by medroxyprogesterone acetate (MPA). These tumors transit through different stages of hormone sensitivity. However, when cells from tumor variants were seeded on plastic, all were stimulated by progestins and inhibited by antiprogestins such as RU486. Furthermore, cells from a RU486-resistant tumor variant recovered antiprogestin sensitivity. A three-dimensional (3D) culture system, by maintaining differential cellular organization that is typical of each tumor variant, may allow for the maintenance of particular hormone responses and thus be appropriate for the study of the effects of specific inhibitors of signaling pathways associated with disease progression. We compared the behavior of tumors growing in vivo and cancer cells ex vi...

We conducted a cross-sectional survey of abortion facilities from professional networks in the United States (US, n = 703) and Canada (n = 94) to estimate the prevalence of medication abortion practices in these settings and to look at regional differences. Administrators responded to questions on gestational limits, while up to five clinicians per facility reported on 2012 medication abortion practice. At the time of fielding, mifepristone was not approved in Canada. 383 (54.5%) US and 78 (83.0%) Canadian facilities participated. In the US, 95.3% offered first trimester medication abortion compared to 25.6% in Canada. While 100% of providers were physicians in Canada, just under half (49.4%) were advanced practice clinicians in the US, which was more common in Eastern and Western states. All Canadian providers used misoprostol; 85.3% with methotrexate. 91.4% of US providers used 200 mg of mifepristone and 800 mcg of misoprostol, with 96.7% reporting home misoprostol administration....

In Nepal medical abortion has been approved for use since 2009. There were many cases coming to Tribhuvan University Teaching Hospital coming with problems and complications following medical abortion. Thus the objective of this study was to analyze the cases that came to TUTH following medical abortion with problems and complications. This is a prospective study conducted in the Department of Obstetrics and Gynecology of TUTH. Study was carried from 1st August 2011 to 30th November 2012. Women who came to TUTH with any complaints following medical abortion were interviewed, examined and treatment provided. Relevant clinical finding were noted. There were a total of 57 cases during the study. Most (66.6%) of the women were in age group 20-29 years age. There were 45 (79%) women who had abortion up to 9 weeks. Medical shop was the main place where most of the women (45.6%) directly come to know about medical abortion. More than 34 (77.2%) received the service from medical shops witho...

Cushing's syndrome (CS) in the pediatric population is challenging to diagnose and treat. Although next-generation medical therapies are emerging for adults with CS, none are currently approved or used in children. Here we describe the first use of mifepristone, a glucocorticoid receptor antagonist, to treat CS in a pediatric subject. The patient, a 14-year-old girl with an 18-month history of metastatic neuroendocrine carcinoma, suffered from fatigue, profound myopathy, irritability, and depression. She was found to have hypertension, hypokalemia, and worsening control of her preexisting type 1 diabetes. In this report, we detail our clinical evaluation that confirmed CS caused by an ectopic adrenocorticotropic hormone secreting tumor. Surgical and radiation therapies were not pursued because of her poor functional status and limited life expectancy, and medical treatment of CS was indicated for symptom relief. Mifepristone treatment provided rapid improvement in glycemic contr...

Transcriptionally active nuclear extracts from human breast carcinoma cells (T47D) were used to compare the action of progestins and several antiprogestins of the 11/S-aryl substituted steroid series on the DNA-binding properties and the trans-activating potential of progesterone ...

The role of the hypothalamus-pituitary-adrenal (HPA) axis in regulating the growth of Mycobacterium avium in Mycobacterium bovis BCG-resistant and -susceptible congenic mice was evaluated. Restraint was used to activate the HPA axis, which resulted in an increase in the level of corticosterone in the plasma. Activation of the HPA axis increased the susceptibility of BALB/c.Bcgs mice to the growth of M. avium. In contrast, the growth of M. avium was not altered in BALB/c.Bcgr mice as a result of HPA activation. Adrenalectomy abolished the effect of HPA activation on mycobacterial growth, as did treatment of the mice with a glucocorticoid receptor antagonist, RU 486. Activation of the HPA axis also resulted in the increased susceptibility of splenic macrophages from Bcgs mice but not from Bcgr mice to M. avium growth in vitro. The production of tumor necrosis factor alpha and of reactive nitrogen intermediates by splenic macrophages from both strains of mice was suppressed as a result...

We explored women's perspectives on using medical abortion, including their reasons for selecting the method, their experiences with it and their thoughts regarding demedicalisation of part or all of the process. Sixty-three women from two urban clinics in India were interviewed within four weeks of abortion completion using a semi-structured in-depth interview guide. While women appreciated the non-invasiveness of medical abortion, other factors influencing method selection were family support and distance from the facility. The degree of medicalisation that women wanted or felt was necessary also depended on the way expectations were set by their providers. Confirmation of abortion completion was a source of anxiety for many women and led to unnecessary interventions in a few cases. Ultimately, experiences depended more on women's expectations about the method, and on the level of emotional and logistic support they received rather than on inherent characteristics of the method. These findings emphasise the circumstances under which women make reproductive choices and underscore the need to tailor service delivery to meet women's needs. Women-centred counselling and care that takes into consideration individual circumstances are needed.

To evaluate the acceptability and efficacy of medical abortion at home up to 63 days' gestation without limits on travel distance to a registered institution. Observational prospective study. Haukeland University Hospital between May 2006 and May 2009. A total of 1018 women requesting abortion before 63 days' gestation who chose medical termination with mifepristone and home administration of misoprostol. The women took 200 mg mifepristone under nurse supervision and self-administered 800 μg misoprostol vaginally 36-48 h later at home. All were contacted by phone for follow-up and assessment of bleeding, pain and acceptability. Evacuation rate, pain, bleeding, acceptability, influence of distance on treatment. Median gestational age was 50 (range 35-63) days and 70 (7.1%) of the women lived more than 60 min travel from the clinic. The rate of completed abortion was 93.6% and surgical evacuation was performed in 50 (4.9%) cases. Two women requested treatment on the day of mis...