-
Contraception Apr 2024
PubMed: 38679275
DOI: 10.1016/j.contraception.2024.110477 -
Clinical and Translational Medicine Apr 2024
Topics: Humans; Female; Mifepristone; Leiomyoma; Simvastatin; Receptors, Progesterone; Signal Transduction; Drug Synergism; Uterine Neoplasms
PubMed: 38649749
DOI: 10.1002/ctm2.1672 -
Journal of Hazardous Materials Jun 2024The occurrence, environmental risks and contribution of organic UV filters to detected (anti-)progestogenic activities were examined in samples of wastewater treatment...
The occurrence, environmental risks and contribution of organic UV filters to detected (anti-)progestogenic activities were examined in samples of wastewater treatment plant influents and effluents, various surface waters and fish from the Czech Republic. Of the 20 targeted UV filters, 15 were detected in the WWTP influent samples, 11 in the effluents, and 13 in the surface water samples. Benzophenone-3, benzophenone-4, and phenyl benzimidazole sulfonic acid (PBSA) were found in all water samples. Octocrylene, UV-327 and 4-methylbenzylidene camphor exceeded the risk quotient of 1 at some sites. In the anti-progestogenic CALUX assay, 10 out of the 20 targeted UV filters were active. Anti-progestogenic activities reaching up to 7.7 ng/L, 3.8 ng/L, and 4.5 ng/L mifepristone equivalents were detected in influents, effluents, and surface waters, respectively. UV filters were responsible for up to 37 % of anti-progestogenic activities in influents. Anti-progestogenic activities were also measured in fish tissues from the control pond and Podroužek (pond with the highest number of detected UV filters) and ranged from 2.2 to 9.5 and 1.9 to 8.6 ng/g dw mifepristone equivalents, respectively. However, only benzophenone was found in fish, but it does not display anti-progestogenic activity and thus could not explain the observed activities.
Topics: Animals; Sunscreening Agents; Water Pollutants, Chemical; Czech Republic; Fishes; Environmental Monitoring; Wastewater; Risk Assessment; Progestins; Ultraviolet Rays
PubMed: 38643577
DOI: 10.1016/j.jhazmat.2024.134338 -
Contraception Apr 2024Routine ultrasound before medication abortion (MAB) may create an impediment to expanding abortion access. This study examines clinical outcomes of MAB without...
OBJECTIVES
Routine ultrasound before medication abortion (MAB) may create an impediment to expanding abortion access. This study examines clinical outcomes of MAB without pretreatment ultrasound evaluation at Planned Parenthood health centers in multiple states.
STUDY DESIGN
We conducted a secondary analysis of data from 23 US-based Planned Parenthood affiliates that provided MAB without pretreatment ultrasound for eligible patients from March 2020 to December 2021. Affiliates aggregated electronic health record data from MABs at ≤77 days gestation (based on self-report of last menstrual period) without a pretreatment ultrasound (N = 18,041). Among MABs with known outcomes (N = 9821), we calculated the incidence rates and 95% confidence intervals (CI) for completed abortion, ongoing pregnancy, subsequent procedure, emergency department/hospital visits associated with MAB, ectopic pregnancies, and gestational duration greater than 77 days.
RESULTS
Among MABs with known outcomes, 96.3% had a complete abortion (95% CI = 95.9%-96.7%), and 2.0% had an ongoing pregnancy (95% CI = 1.7%-2.3%). Four percent had a subsequent procedure (95% CI = 3.6%-4.4%), and 2.3% had a documented emergency department/hospital visit (95% CI = 2.0%-2.6%). Less than 1% had a confirmed ectopic pregnancy (0.15%, 95% CI = 0.09%-0.25%) and had a gestational duration later identified to be greater than 77 days (0.13%, 95% CI = 0.05%-0.29%).
CONCLUSIONS
Our calculated incidence rates of clinical outcomes align with rates from the previous literature on MAB and from the emerging literature on MAB without pretreatment ultrasonography. Findings from this analysis suggest that MAB without pretreatment ultrasound is safe and effective for eligible patients.
IMPLICATIONS
This large US study found that medication abortion without pretreatment ultrasonography results in similar clinical outcomes to prepandemic models that include pretreatment ultrasonography. Medication abortion without a pretreatment ultrasound may be adopted by abortion providers seeking to expand options for their patients as access to abortion continues to erode.
PubMed: 38641157
DOI: 10.1016/j.contraception.2024.110469 -
Contraception Apr 2024To evaluate the implementation of mifepristone and misoprostol for medical management of early pregnancy loss (EPL) in emergency departments (EDs) by comparing...
Medical management of early pregnancy loss with mifepristone and misoprostol in emergency departments compared to a Complex Family Planning office: Implementation of a COVID-19 institutional policy change.
OBJECTIVES
To evaluate the implementation of mifepristone and misoprostol for medical management of early pregnancy loss (EPL) in emergency departments (EDs) by comparing efficacy, complication, and follow-up rates for patients treated in EDs to the Complex Family Planning (CFP) outpatient office.
STUDY DESIGN
In COVID-19's first wave, we expanded medical management of EPL to our EDs. This retrospective study evaluated 72 patients receiving mifepristone and misoprostol for EPL from April 1, 2020 to March 31, 2021, comparing treatment success, safety outcomes, and follow-up rates by location.
RESULTS
Thirty-three (46%) patients received care in the ED and 39 (54%) at CFP. Treatment success was lower in EDs (23, 70%) compared to CFP (34, 87%), but after adjusting for insurance status and pregnancy type (miscarriage, uncertain viability, unknown location), this was not significant: adjusted odds ratio 0.48 (95% CI 0.13-1.81). More ED patients underwent emergent interventions (3 vs 0) including two emergent uterine aspirations, one uterine artery embolization, and two blood transfusions. Two cases were attributed to misdiagnosis (cesarean scar and cervical ectopic pregnancies interpreted as incomplete miscarriages) and one to guideline nonadherence. No complications occurred in the CFP group. Follow-up rates were over 80% in both groups. More ED patients engaged in telehealth follow-up (67% vs 18%, p ≤ 0.0001).
CONCLUSIONS
In this small sample, we observed a trend toward less successful treatment in the ED compared to the CFP office. Both correctly making uncommon diagnoses and adhering to new guidelines presented implementation challenges.
IMPLICATIONS
Implementing mifepristone and misoprostol for EPL in our EDs achieved lower rates of pregnancy resolution compared to outpatient management. Complex uncommon diagnoses and implementing new care pathways in EDs may have contributed to complications and highlighted opportunities for improvement. Additional studies are needed to further quantify safety outcomes for EPL management in EDs.
PubMed: 38641155
DOI: 10.1016/j.contraception.2024.110467 -
Georgian Medical News Feb 2024Cervical ripening is a critical component of normal parturition. There are substantial variations in labour induction (IOL) techniques around the world. Mifepristone...
Cervical ripening is a critical component of normal parturition. There are substantial variations in labour induction (IOL) techniques around the world. Mifepristone causes the termination of unwanted pregnancies, but there is a lack of consensus on its use for labour induction. The purpose of our study was to compare the combination of Mifepristone and Misoprostol with the combination of a Foley balloon and Misoprostol for labour induction. The study included 175 pregnant women, with gestational age 37-42 weeks. In the study group - 88 pregnant aged 21-35 (28.56±3.23), a combination of Mifepristone-Misoprostol was used. A combination of Foley catheter and Misoprostol was used in the control group - 87 pregnant aged 21-35 (29.48±3.03). The outcomes were assessed. In the study group the rate of vaginal delivery was higher and the frequency of cesarean section was lower compared to the control group (75 vs. 72, and 13 vs. 15, respectively); The total duration of labour was shorter in the study group (p<0,05); There was no difference between groups in the incidences of neonatal morbidity on the first and the fifth minute of life (p>0,05); The pain level was significantly low in the study group compared to the control group (5±0,75 vs. 8±0,96) and no cervical laceration was revealed in the study group. The Mifepristone - Misoprostol combination has advantages over the Foley balloon - Misoprostol combination for induction of labour regarding reduction in pain intensity, duration of labour, and cervical laceration.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Cesarean Section; Lacerations; Mifepristone; Misoprostol; Labor, Induced; Soft Tissue Injuries
PubMed: 38609105
DOI: No ID Found -
Expert Opinion on Emerging Drugs Apr 2024Alcohol Use Disorder (AUD) poses an ongoing significant global health burden. AUD is highly prevalent and affects not only the individuals with AUD, but also their... (Review)
Review
INTRODUCTION
Alcohol Use Disorder (AUD) poses an ongoing significant global health burden. AUD is highly prevalent and affects not only the individuals with AUD, but also their communities and society at large. Even though pharmacotherapy is an integral part of AUD treatment, the few available substances show limited efficacy and limited clinical impact. Thus, there is a need for new innovative pharmacotherapeutic approaches.
AREAS COVERED
This paper provides a comprehensive review of drugs approved for the treatment of AUD as well as those currently in phase II and III development. Data from recent clinical trials has been reviewed and supplemented by additional literature based on a systematic search of the PubMed database and clinical trials registries. Compounds discussed include disulfiram, naltrexone, nalmefene, acamprosat, baclofen, sodium oxybate, doxazosin, varenicline, zonisamide, gabapentin, apremilast, ibudilast, ivermectin, tolcapone, mifepristone, suvorexant, ketamine, psilocybin, semaglutide, oxytocin and cannabidiol.
EXPERT OPINION
Even though the majority of the discussed compounds lack sufficient evidence to support their efficacy, multiple promising new treatment options are currently under investigation. Future research has to consider specific phenotypes and subgroups of AUD as well as a possible enhancement of the effects of psychotherapy through combination with pharmacotherapy. Practitioners should be encouraged to use available compounds to support existing therapeutic regimens.
PubMed: 38606899
DOI: 10.1080/14728214.2024.2342951 -
Reproductive Sciences (Thousand Oaks,... Apr 2024The purpose of this study was to investigate the effect of G-CSF on the endometrial receptivity of implantation failure mice. Sixty female mice were treated...
The purpose of this study was to investigate the effect of G-CSF on the endometrial receptivity of implantation failure mice. Sixty female mice were treated mifepristone to establish an implant failure model. The treatment groups received different doses of G-CSF. Endometrial tissue and serum were collected on day 5 after mating. The abundance of pinopodes on the endometrium was observed by scanning electron microscopy. The expressions of LPAR3, COX2, and HOXA10 were detected by RT-qPCR and Western blotting. Serum levels of E2, P, VEGF, LIF, TNF-α and IL-10 were measured by ELISA. The expressions of VEGF, CD34, CD57, TNF-α, and IL-10 were assessed by immunohistochemistry. Immunofluorescence analysis was performed to determine the number of CD57, Treg, and Th17 cells. G-CSF increased implantation and pregnancy rates of mifepristone-induced implantation failure mice, with the most significant effect seen at the intermediate dose. G-CSF increased the serum levels of E2 and P, the abundance of endometrial pinopodes, and the level of LIF in the endometrium. It also promoted the expression of VEGF, HOXA10, LPAR3, and COX2. Moreover, G-CSF reduced the level of CD57 cells and the ratio of Th17/Treg cells in endometrium. G-CSF reduced the inflammatory factor TNF-α, but IL-10 did not change significantly. G-CSF can enhance embryo implantation rate and pregnancy rate and improve endometrial receptivity by attenuating degeneration of pinopodes, upregulating estrogen and progesterone, facilitating angiogenesis, maintaining immune cell homeostasis, and reducing the production of inflammatory cytokines in implantation failure mouse.
PubMed: 38600416
DOI: 10.1007/s43032-024-01527-6 -
Environmental Science and Pollution... Apr 2024This work proposes the use of multi-criteria decision analysis (MCDA) to select a more environmentally friendly analytical procedure. TOPSIS, which stands for Technique...
Multi-criteria decision analysis: technique for order of preference by similarity to ideal solution for selecting greener analytical method in the determination of mifepristone in environmental water samples.
This work proposes the use of multi-criteria decision analysis (MCDA) to select a more environmentally friendly analytical procedure. TOPSIS, which stands for Technique for Order of Preference by Similarity to Ideal Solution, is an example of a MCDA method that may be used to rank or select best alternative based on various criteria. Thirteen analytical procedures were used in this study as TOPSIS input choices for mifepristone determination in water samples. The input data, which consisted of these choices, was described using assessment criteria based on 12 principles of green analytical chemistry (GAC). Based on the objective mean weighting (MW), the weights for each criterion were assigned equally. The most preferred analytical method according to the ranking was solid phase extraction with micellar electrokinetic chromatography (SPE-MEKC), while solid phase extraction combined with ultra-high performance liquid chromatography tandem mass spectrometry (SPE-UHPLC-MS/MS) was ranked last. TOPSIS ranking results were also compared to the green metrics NEMI, Eco-Scale, GAPI, AGREE, and AGREEprep that were used to assess the greenness of thirteen analytical methods for mifepristone determination. The results demonstrated that only the AGREE metric tool correlated with TOPSIS; however, there was no correlation with other metric tools. The analysis results suggest that TOPSIS is a very useful tool for ranking or selecting the analytical procedure in terms of its greenness and that it can be easily integrated with other green metrics tools for method greenness assessment.
Topics: Mifepristone; Water Pollutants, Chemical; Decision Support Techniques; Solid Phase Extraction; Chromatography, High Pressure Liquid; Tandem Mass Spectrometry
PubMed: 38578593
DOI: 10.1007/s11356-024-32961-3 -
Stem Cells and Development Jun 2024The aim of this article was to investigate whether exosomes derived from bone marrow mesenchymal stem cells repair damaged endometrial stromal cells (EnSCs) through the...
The aim of this article was to investigate whether exosomes derived from bone marrow mesenchymal stem cells repair damaged endometrial stromal cells (EnSCs) through the miR-99b-5p/PCSK9 axis. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) were isolated by ultracentrifugation and characterized using transmission electron microscopy and nanoflow cytometry. A mifepristone-induced EnSC injury model was established in vitro, and the uptake of BMSC-exos was assessed. EnSCs were divided into three groups: the normal group (ctrl), EnSC injury group (model), and BMSC-exo treatment group. The effects of BMSC-exos on EnSC proliferation, apoptosis, and vascular endothelial growth factor (VEGF) expression were assessed by coculturing MSC-exos with endometrial cells. Furthermore, high-throughput sequencing was used to identify differentially expressed genes (DEGs). Through bioinformatics analysis, reverse transcription-quantitative polymerase chain reaction, western blotting, the CCK8 assay, immunohistochemistry, and dual-luciferase experiments, the potential mechanism by which BMSC-exos-derived miRNAs repair EnSC injury was studied. BMSC-exos expressed the marker proteins CD9 and CD63. Laser confocal microscopy showed that BMSC-exos could enter damaged EnSCs. In the BMSC-exos-EnSC coculture group compared with the model group, BMSC-exos significantly increased the proliferation of damaged EnSCs and inhibited cell apoptosis in a dose-dependent manner. The expression levels of Caspase-3, Caspase-9, Bax, and VEGF mRNA were significantly downregulated in the BMSC-exos-EnSC coculture group, whereas Bcl-2 expression was upregulated. We identified 28 overlapping DEGs between the model and ctrl groups and between the BMSC-exo and model groups. Transfection with miR-99b-5p mimics significantly decreased PCSK9 gene expression and inhibited the expression of the autophagy-related proteins Beclin-1 and LC3-II/I and apoptosis, thereby promoting EnSC proliferation. Transfection with a miR-99b-5p inhibitor showed the opposite effects. Beclin-1, LC3-II/I, and PCSK9 expression in the thin endometrium was significantly increased. miR-99b-5p promoted cell proliferation by targeting PCSK9. BMSC-exos promoted endometrial proliferation, and miR-99b-5p inhibited cell apoptosis and promoted EnSC proliferation by targeting PCSK9, providing a new target for the treatment of thin endometrium.
Topics: Mesenchymal Stem Cells; MicroRNAs; Female; Endometrium; Exosomes; Humans; Proprotein Convertase 9; Cell Proliferation; Apoptosis; Cell Survival; Cells, Cultured; Vascular Endothelial Growth Factor A
PubMed: 38573013
DOI: 10.1089/scd.2023.0259