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Nigerian Journal of Clinical Practice Feb 2024Intrauterine foetal death (IUFD) is an unpleasant pregnancy outcome and prompt delivery of the dead foetus is usually desired by mothers. Unfortunately, spontaneous... (Randomized Controlled Trial)
Randomized Controlled Trial
A Comparison of the Efficacy and Safety of Mifepristone and Misoprostol Versus Misoprostol alone for Induction of Labour in Nigerian Women with Intrauterine Fetal Death: A Triple Blind Randomized Controlled Trial.
BACKGROUND
Intrauterine foetal death (IUFD) is an unpleasant pregnancy outcome and prompt delivery of the dead foetus is usually desired by mothers. Unfortunately, spontaneous labour and delivery may not occur early and prolonged retention of the dead foetus in utero is life-threatening. Many of the agents currently used for the induction of labour may result in a prolonged delivery process.
OBJECTIVES
To compare the efficacy and safety of mifepristone and misoprostol versus misoprostol alone for induction of labour in women with intrauterine foetal death.
MATERIALS AND METHODS
This was a triple-blind randomized controlled trial. Eighty women were randomized into two groups. The intervention group received a single oral dose of 200 mg mifepristone, followed by 6-hourly 50 μg misoprostol vaginal insertion, after 24-hour intervals. The control group received a placebo, followed by 6-hourly 50 μg misoprostol vaginal insertion, after 24-hour intervals. The primary outcome measure was the induction to delivery interval.
RESULTS
Maternal age, gestational age, parity and pre-induction bishop's score were comparable between the two groups. The mean induction to the delivery interval in the intervention group was significantly less in the intervention group than the control group (18.78 ± 6.51 hours versus 37.10 ± 10.10; P < 0.001). The total dose of misoprostol required for induction of labour; the need for oxytocin augmentation of labour; and the observed side effects of misoprostol were all significantly less in intervention group than control group (P < 0.001; P < 0.01; and P = 0.03, respectively).
CONCLUSION
The combination of mifepristone and misoprostol has greater efficacy and better safety profile than the use of misoprostol alone for induction of labour. This combination should be considered when induction of labour is indicated for IUFD.
Topics: Female; Humans; Pregnancy; Administration, Intravaginal; Fetal Death; Labor, Induced; Mifepristone; Misoprostol; Oxytocics; Pregnancy Outcome; Drug Combinations
PubMed: 38409142
DOI: 10.4103/njcp.njcp_786_22 -
Cureus Jan 2024Cervical ectopic pregnancy is the rarest kind of ectopic pregnancy, and it is known as the implantation of an embryo into the cervical mucosa. It is commonly associated...
Cervical ectopic pregnancy is the rarest kind of ectopic pregnancy, and it is known as the implantation of an embryo into the cervical mucosa. It is commonly associated with complications such as hemorrhage from the cervix and can lead to severe consequences if it is not treated early. For this reason, the treatment for a cervical pregnancy often requires an abdominal hysterectomy. To avoid such radical management, several conservative methods of termination have been used. In this paper, we report a complex management of one of our ectopic cervical cases, which includes embolization of the uterine arteries, treatment with methotrexate and mifepristone, evacuation of the pregnancy followed by local hemostatic sutures and application of a balloon in the cervix. The post-operative period was uneventful. After a three-day postoperative stay, the patient was discharged. The management options employed in the presented case achieved the goal of preserving fertility for our patient. There are no specific guidelines for the treatment of cervical pregnancies in advanced gestational age.
PubMed: 38406068
DOI: 10.7759/cureus.52771 -
Biology Feb 2024In aquaculture, stress can negatively affect fish growth. For years, the cortisol hormone has been thought to play both glucocorticoid and mineralocorticoid functions....
In aquaculture, stress can negatively affect fish growth. For years, the cortisol hormone has been thought to play both glucocorticoid and mineralocorticoid functions. Nevertheless, recent research has suggested that 11-deoxycorticosterone (DOC) released during stress could contribute to cortisol actions, though this process is still misunderstood. Here, we evaluated the DOC effects on physiological and early transcriptional responses by RNA-seq. Juvenile rainbow trout were treated with DOC and/or glucocorticoids (mifepristone) or mineralocorticoid (eplerenone) receptor antagonists. Subsequently, plasma was collected, and cDNA libraries were generated from the gills of vehicle (control), DOC, mifepristone, mifepristone with DOC, eplerenone, and eplerenone with DOC groups. Calcium and phosphate levels in plasma were changed. Results revealed 914 differentially expressed transcripts (DETs) induced by DOC compared with control, mainly associated with sodium ion transmembrane transport, gluconeogenesis, negative regulation of transmembrane transport, and activation of innate immune response. DOC versus eplerenone with DOC comparison displayed 444 DETs related to cell-cell junction organization, canonical glycolysis, positive regulation of immune response, and potassium ion transport. Conversely, no DETs were detected in DOC versus mifepristone with DOC comparison. These data suggest that DOC has a relevant role in gill stress response and ion transport, which is differentially regulated by mineralocorticoid receptors.
PubMed: 38392325
DOI: 10.3390/biology13020107 -
Molecular & Cellular Proteomics : MCP Mar 2024Exogenous glucocorticoids are frequently used to treat inflammatory disorders and as adjuncts for the treatment of solid cancers. However, their use is associated with...
Exogenous glucocorticoids are frequently used to treat inflammatory disorders and as adjuncts for the treatment of solid cancers. However, their use is associated with severe side effects and therapy resistance. Novel glucocorticoid receptor (GR) ligands with a patient-validated reduced side effect profile have not yet reached the clinic. GR is a member of the nuclear receptor family of transcription factors and heavily relies on interactions with coregulator proteins for its transcriptional activity. To elucidate the role of the GR interactome in the differential transcriptional activity of GR following treatment with the selective GR agonist and modulator dagrocorat compared to classic (ant)agonists, we generated comprehensive interactome maps by high-confidence proximity proteomics in lung epithelial carcinoma cells. We found that dagrocorat and the antagonist RU486 both reduced GR interaction with CREB-binding protein/p300 and the mediator complex compared to the full GR agonist dexamethasone. Chromatin immunoprecipitation assays revealed that these changes in GR interactome were accompanied by reduced GR chromatin occupancy with dagrocorat and RU486. Our data offer new insights into the role of differential coregulator recruitment in shaping ligand-specific GR-mediated transcriptional responses.
Topics: Humans; Receptors, Glucocorticoid; Chromatin; Mifepristone; Mediator Complex; Glucocorticoids; Dexamethasone; Benzamides; Phenanthrenes
PubMed: 38387774
DOI: 10.1016/j.mcpro.2024.100741 -
Medicine Feb 2024Uterine prolapse is a rare complication of pregnancy, and there is still no consensus on the choice of delivery method.
BACKGROUND
Uterine prolapse is a rare complication of pregnancy, and there is still no consensus on the choice of delivery method.
METHODS
The patient's reproductive history included an abortion and eutocic delivery of a girl weighing 3200 g; the current pregnancy was the third pregnancy. Her cervical region was outside the vaginal opening and was red in color, with evident enlargement (6 × 4 cm) and a broken surface. The cervical area also showed white discharge. According to her Transvaginal ultrasonography revealed a fetus in the uterine cavity at approximately 19 weeks of gestation. Gynecological examination revealed prolapse of both the anterior and posterior vaginal walls. Evaluation of the pelvic organ prolapse-Q scores showed that the patient had uterine prolapse at stage IV.
RESULTS
Vaginal delivery was performed smoothly after oral administration mifepristone and misoprostol tablets for a few days, obtaining a dead female fetus in cephalic, 25 cm in length. The cervix of the pregnant woman did not prolapse during the delivery.
CONCLUSION
For pregnancy with uterine prolapse and cervical incarceration, transvaginal delivery is a potential treatment option. Maintenance of cervical retraction and oral mifepristone administration with misoprostol tablets is crucial during this delivery. This treatment can minimize the risk of cervical lacerations and uterine rupture, helping surgeons to complete the operation successfully.
Topics: Humans; Pregnancy; Female; Misoprostol; Pregnancy Trimester, Second; Mifepristone; Uterine Prolapse; Cervix Uteri; Incarceration; Delivery, Obstetric
PubMed: 38363949
DOI: 10.1097/MD.0000000000037202 -
Nature Medicine Apr 2024Telehealth abortion has become critical to addressing surges in demand in states where abortion remains legal but evidence on its effectiveness and safety is limited....
Telehealth abortion has become critical to addressing surges in demand in states where abortion remains legal but evidence on its effectiveness and safety is limited. California Home Abortion by Telehealth (CHAT) is a prospective study that follows pregnant people who obtained medication abortion via telehealth from three virtual clinics operating in 20 states and Washington, DC between April 2021 and January 2022. Individuals were screened using a standardized no-test protocol, primarily relying on their medical history to assess medical eligibility. We assessed effectiveness, defined as complete abortion after 200 mg mifepristone and 1,600 μg misoprostol (or lower) without additional intervention; safety was measured by the absence of serious adverse events. We estimated rates using multivariable logistic regression and multiple imputation to account for missing data. Among 6,034 abortions, 97.7% (95% confidence interval (CI) = 97.2-98.1%) were complete without subsequent known intervention or ongoing pregnancy after the initial treatment. Overall, 99.8% (99.6-99.9%) of abortions were not followed by serious adverse events. In total, 0.25% of patients experienced a serious abortion-related adverse event, 0.16% were treated for an ectopic pregnancy and 1.3% abortions were followed by emergency department visits. There were no differences in effectiveness or safety between synchronous and asynchronous models of care. Telehealth medication abortion is effective, safe and comparable to published rates of in-person medication abortion care.
Topics: Pregnancy; Female; Humans; United States; Prospective Studies; Abortion, Induced; Mifepristone; Misoprostol; Abortion, Spontaneous; Telemedicine
PubMed: 38361123
DOI: 10.1038/s41591-024-02834-w -
Journal of Psychopharmacology (Oxford,... Mar 2024Addiction to tobacco and nicotine products has adverse health effects and afflicts more than a billion people worldwide. Therefore, there is an urgent need for new...
BACKGROUND
Addiction to tobacco and nicotine products has adverse health effects and afflicts more than a billion people worldwide. Therefore, there is an urgent need for new treatments to reduce tobacco and nicotine use. Glucocorticoid receptor blockade shows promise as a novel treatment for drug abuse and stress-related disorders.
AIM
These studies aim to investigate whether glucocorticoid receptor blockade with mifepristone diminishes the reinforcing properties of nicotine in rats with intermittent or daily long access to nicotine.
METHODS
The rats self-administered 0.06 mg/kg/inf of nicotine for 6 h per day, with either intermittent or daily access for 4 weeks before treatment with mifepristone. Daily nicotine self-administration models regular smoking, while intermittent nicotine self-administration models occasional smoking. To determine whether the rats were dependent, they were treated with the nicotinic acetylcholine receptor antagonist mecamylamine, and somatic signs were recorded.
RESULTS
The rats with intermittent access to nicotine had a higher level of nicotine intake per session than those with daily access but only the rats with daily access to nicotine showed signs of physical dependence. Furthermore, mecamylamine increased nicotine intake during the first hour of access in rats with daily access but not in those with intermittent access. Mifepristone decreased total nicotine intake in rats with intermittent and daily access to nicotine. Moreover, mifepristone decreased the distance traveled and rearing in the open field test and operant responding for food pellets.
CONCLUSION
These findings indicate that mifepristone decreases nicotine intake but this effect may be partially attributed to the sedative effects of mifepristone.
Topics: Humans; Rats; Animals; Nicotine; Mecamylamine; Mifepristone; Smoking; Receptors, Glucocorticoid; Tobacco Use Disorder; Substance Withdrawal Syndrome; Rats, Wistar; Self Administration; Dose-Response Relationship, Drug
PubMed: 38332661
DOI: 10.1177/02698811241230255 -
Frontiers in Immunology 2023Ma Xing Shi Gan Decoction (MXSGD) is a traditional remedy for treating lung injuries that was developed by the Typhoid and Fever School of Pharmaceutical Biology. It has...
CONTEXT
Ma Xing Shi Gan Decoction (MXSGD) is a traditional remedy for treating lung injuries that was developed by the Typhoid and Fever School of Pharmaceutical Biology. It has antitussive and expectorant effects, anti-inflammatory, antiviral, regulates the body's immunity, etc.
AIM
The aim of this study is to investigate whether MXSGD can ameliorate cyclosporine A (CsA)-induced hypoimmunity lung injury by regulating microflora metabolism. Methods: Establishment of a model for CsA-induced hypoimmunity lung injury. Using 16S rRNA high-throughput sequencing and LC-MS, the effects of MXSGD on gut flora and lung tissue microecology of mice with CsA-induced hypoimmunity were investigated.
RESULTS
MXSGD was able to preserve lung tissue morphology and structure, reduce serum inflammatory marker expression and protect against CsA-induced lung tissue damage. Compared to the model, MXSGD increased beneficial gut bacteria: and ; decreased intestinal pathogens: ; reduced the abundance of and , promoted the production of and , and then promoted the lung flora to produce short-chain fatty acids. MXSGD was able to enhance the expression of serum metabolites such as Americine, 2-hydroxyhexadecanoylcarnitine, Emetine, All-trans-decaprenyl diphosphate, Biliverdin-IX-alpha, Hordatin A and N-demethyl mifepristone in the CsA-induced hypoimmunity lung injury model.
CONCLUSION
MXSGD can restore gut and lung microbiota diversity and serum metabolite changes to inhibit inflammation, ameliorate CsA-induced hypoimmunity lung injury.
Topics: Animals; Mice; Lung Injury; Cyclosporine; RNA, Ribosomal, 16S; Acinetobacter; Immunologic Deficiency Syndromes; Drugs, Chinese Herbal
PubMed: 38259457
DOI: 10.3389/fimmu.2023.1298416 -
Cancer Cell International Jan 2024Although meningioma is the most common primary brain tumor, treatments rely on surgery and radiotherapy, and recurrent meningiomas have no standard therapeutic options...
BACKGROUND
Although meningioma is the most common primary brain tumor, treatments rely on surgery and radiotherapy, and recurrent meningiomas have no standard therapeutic options due to a lack of clinically relevant research models. Current meningioma cell lines or organoids cannot reflect biological features of patient tumors since they undergo transformation along culture and consist of only tumor cells without microenvironment. We aim to establish patient-derived meningioma organoids (MNOs) preserving diverse cell types representative of the tumor microenvironment.
METHODS
The biological features of MNOs were evaluated using WST, LDH, and collagen-based 3D invasion assays. Cellular identities in MNOs were confirmed by immunohistochemistry (IHC). Genetic alteration profiles of MNOs and their corresponding parental tumors were obtained by whole-exome sequencing.
RESULTS
MNOs were established from four patients with meningioma (two grade 1 and two grade 2) at a 100% succession rate. Exclusion of enzymatic dissociation-reaggregation steps endowed MNOs with original histology and tumor microenvironment. In addition, we used a liquid media culture system instead of embedding samples into Matrigel, resulting in an easy-to-handle, cost-efficient, and time-saving system. MNOs maintained their functionality and morphology after long-term culture (> 9 wk) and repeated cryopreserving-recovery cycles. The similarities between MNOs and their corresponding parental tumors were confirmed by both IHC and whole-exome sequencing. As a representative application, we utilized MNOs in drug screening, and mifepristone, an antagonist of progesterone receptor, showed prominent antitumor efficacy with respect to viability, invasiveness, and protein expression.
CONCLUSION
Taken together, our MNO model overcame limitations of previous meningioma models and showed superior resemblance to parental tumors. Thus, our model could facilitate translational research identifying and selecting drugs for meningioma in the era of precision medicine.
PubMed: 38238738
DOI: 10.1186/s12935-024-03225-4 -
Fertility and Sterility May 2024To compare the success rates of medical management using a combined mifepristone and misoprostol protocol in cases of early pregnancy loss (EPL) between women who... (Comparative Study)
Comparative Study
OBJECTIVE
To compare the success rates of medical management using a combined mifepristone and misoprostol protocol in cases of early pregnancy loss (EPL) between women who conceived without medical assistance and those who conceived through in vitro fertilization (IVF), after fresh or frozen embryo transfer, and evaluate for the predictive factors of success, time to first passage of tissue, and time to complete resolution of pregnancy.
DESIGN
Retrospective cohort study.
SETTING
University hospital.
PATIENT(S)
Women who presented with EPL below 13 weeks of gestation between June 2013 and July 2021 who were managed medically with mifepristone 200 mg orally and misoprostol 800 mcg vaginally were included in the study.
INTERVENTION(S)
Medical management with mifepristone and misoprostol; conception without medical assistance vs. post-IVF, after fresh or frozen embryo transfer.
MAIN OUTCOME MEASURE(S)
We evaluated overall success and performed subgroup analysis according to the mode of conception and compared fresh vs. frozen-thawed embryo transfers for IVF pregnancies. In all groups, we also calculated success according to gestational age and compared the time to first passage of tissue. The potential predictive factors of treatment success were analyzed. The side effects and complications of treatment were recorded.
RESULT(S)
A total of 930 women were included in the study, 99 (11%) of whom achieved pregnancy after IVF. The overall success of medical treatment was 89% with no statistically significant difference according to the mode of conception (89% vs. 89%) or type of transfer (fresh 89% vs. frozen 89%). Only lower gestational age by sonography was independently predictive of treatment success, showing a negative regression coefficient of β = -0.333 and an odds ratio of 0.717. The mean time to first passage of tissue was 5.0 ± 2.1 hours. Altogether, 666 women (72%) showed pregnancy resolution on the day of medication administration, an additional 110 women at 1-week follow-up, and a further 74 women after ≥4 weeks on ultrasound.
CONCLUSION(S)
Medical management of EPL with mifepristone and misoprostol is a highly successful treatment option that results in completed abortion in a timely fashion in both pregnancies conceived without medical assistance and those conceived after IVF.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Adult; Mifepristone; Fertilization in Vitro; Misoprostol; Abortion, Spontaneous; Embryo Transfer; Treatment Outcome; Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Administration, Oral
PubMed: 38211763
DOI: 10.1016/j.fertnstert.2024.01.011