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Heliyon May 2024To investigate the protective effects against abnormal uterine bleeding (AUB) and possible mechanisms of Xue Ping tablets (XPT) using a rat model.
OBJECTIVE
To investigate the protective effects against abnormal uterine bleeding (AUB) and possible mechanisms of Xue Ping tablets (XPT) using a rat model.
METHODS
A total of 58 unmated female and 25 male SPF SD rats aged 8-9 weeks were selected. Eight unmated female rats were selected as the blank control group according to the complete random method. The other 50 rats were mated in a female/male ratio of 2:1. In the morning after mating, vaginal smears were collected. Presence of vaginal plug or sperm was regarded as the first day of pregnancy. All pregnant rats were given 8.3 mg/kg of mifepristone by gavage at 8:00 a.m. and 100 μg/kg misoprostol by gavage at 6:00 p.m. on the seventh day of pregnancy to induce incomplete abortion, thereby establishing a rat model of AUB. Forty rats were randomly divided into model, low- (220 mg/kg), medium- (441 mg/kg), high-dose (882 mg/kg) XPT, and positive control groups. The positive group was given 130 mg/kg Gong Xue Ning (GXN). The model group and the blank group were given an equal amount of distilled water.
RESULTS
Compared with the model group, the volume of bleeding in the positive and middle- and high-dose XPT groups decreased ( < 0.05). Moreover, compared with the model group, the progesterone levels in the positive and XPT groups were significantly increased. Immunohistochemistry showed that XPT significantly decreased the expression levels of VEGF, -ERK, NF-κB, SAA, MMP-2, MMP-9, TIMP-1, TIMP-2 and TIMP-3. WB results showed that XPT significantly decreased the expression levels of -ERK, MMP-9, NF-κB, MMP-2 and VEGF. QRT-PCR results showed that XPT significantly decreased the expression levels of VEGF, NF-κB, SAA, MMP-2, TIMP-1, TIMP-2 and TIMP-3 ( < 0.05).
CONCLUSIONS
XPT could reduce AUB by inhibiting the inflammatory factors involved in the VEGF-ERK1/2 pathway.
PubMed: 38694046
DOI: 10.1016/j.heliyon.2024.e30079 -
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 -
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 -
Cureus Mar 2024One of the rarest types of ectopic pregnancy, with an incidence of 1:1,800, is cesarean scar ectopic pregnancy. Here, we report the case of a 28-year-old woman who had...
One of the rarest types of ectopic pregnancy, with an incidence of 1:1,800, is cesarean scar ectopic pregnancy. Here, we report the case of a 28-year-old woman who had undergone two previous cesarean sections. She arrived at our labor room with per vaginal spotting and abdominal pain with an ultrasound that revealed a cesarean scar ectopic pregnancy. The initial beta-human chorionic gonadotropin (β-hCG) value upon admission was 27,133 mIU/mL. Her ultrasound findings were confirmed with magnetic resonance imaging. Opting for combined medical management, we successfully treated her using systemic methotrexate and mifepristone, avoiding surgical intervention despite high β-hCG values. There is currently no established standardized treatment for cesarean scar ectopic pregnancies, and we feel that treatment must be tailored to every patient's individual needs. Our experience suggests that combining mifepristone and systemic methotrexate can be an effective approach with better curative effects, emphasizing the need for further research.
PubMed: 38571849
DOI: 10.7759/cureus.55481 -
Cellular & Molecular Biology Letters Mar 2024Both glucocorticoid receptor and peroxisome proliferator-activated receptor-γ (PPARγ) play a critical role in adipocyte differentiation. Mifepristone is not only an...
BACKGROUND
Both glucocorticoid receptor and peroxisome proliferator-activated receptor-γ (PPARγ) play a critical role in adipocyte differentiation. Mifepristone is not only an antagonist of the glucocorticoid receptor but also an agonist of PPARγ. Therefore, the present study investigated the effect of mifepristone on adipocyte differentiation.
METHODS
Mouse 3T3-L1 cells were used as a model for adipocyte differentiation. The lipid droplet formation was evaluated with Bodipy493/503 staining and the expression of adipocyte markers [adiponectin and adipocyte fatty acid binding protein-4 (Fabp4)] was evaluated with quantitative PCR and immunoblot analyses for indication of adipocyte differentiation. siRNA and neutralizing antibodies were used to elucidate the molecular mechanism of mifepristone-induced adipocyte differentiation. Luciferase reporter assay was used to examine the effect of mifepristone on the promoter activity of PPAR-response element (PPRE). The DNA microarray analysis was used to characterize the transcriptome of the mifepristone-induced adipocytes. In vivo adipogenic effect of mifepristone was examined in mice.
RESULTS
Mifepristone not only enhanced adipocyte differentiation induced by the conventional protocol consisting of insulin, dexamethasone and 3-isobutyl-1-methylxanthine but also induced adipocyte differentiation alone, as evidenced by lipid droplets formation and induction of the expression of adiponectin and Fabp4. These effects were inhibited by an adiponectin-neutralizing antibody and a PPARγ antagonist. Mifepristone activated the promoter activity of PPRE in a manner sensitive to PPARγ antagonist. A principal component analysis (PCA) of DNA microarray data revealed that the mifepristone-induced adipocytes represent some characteristics of the in situ adipocytes in normal adipose tissues to a greater extent than those induced by the conventional protocol. Mifepristone administration induced an increase in the weight of epididymal, perirenal and gluteofemoral adipose tissues.
CONCLUSIONS
Mifepristone alone is capable of inducing adipocyte differentiation in 3T3-L1 cells and adipogenesis in vivo. PPARγ plays a critical role in the mifepristone-induced adipocyte differentiation. Mifepristone-induced adipocytes are closer to the in situ adipocytes than those induced by the conventional protocol. The present study proposes a single treatment with mifepristone as a novel protocol to induce more physiologically relevant adipocytes in 3T3-L1 cells than the conventional protocol.
Topics: Mice; Animals; Adiponectin; Mifepristone; PPAR gamma; 3T3-L1 Cells; Receptors, Glucocorticoid; Cell Differentiation; Adipogenesis; Adipocytes
PubMed: 38553665
DOI: 10.1186/s11658-024-00559-9 -
Cancers Mar 2024Tissue-specificity for fimbrial fallopian tube ovarian carcinogenesis remains largely unknown in mutation carriers. We aimed to assess the cell autonomous and...
BACKGROUND
Tissue-specificity for fimbrial fallopian tube ovarian carcinogenesis remains largely unknown in mutation carriers. We aimed to assess the cell autonomous and cell-nonautonomous implications of a germline mutation in the context of cancer immunosurveillance of CD3 CD56 natural killer (NK) cells.
METHODS
Premenopausal mutation carriers versus age-matched non-carriers were compared. Daily urinary 5β-pregnanediol levels were used to determine progesterone metabolomics across an ovarian cycle. Using peripherally acquired NK cells the cell-mediated cytotoxicity of tumor targets (OVCAR-3, K-562) was determined using live cellular impedance (xCELLigence) and multicolor flow cytometry. Hypoxia-inducible factor 1-alpha (HIF-1α) immunohistochemistry of cancer-free fallopian tube specimens allowed a comparison of proximal versus distal portions. Utilizing these findings the role of environmental factors relevant to the fimbrial fallopian tube (progesterone, hypoxia) on NK cell functional activity were studied in an ovarian phase-specific manner.
RESULTS
mutation carriers demonstrate a differential progesterone metabolome with a phase-specific reduction of peripheral NK cell functional activity. Progesterone exposure further impairs NK cell-mediated cytotoxicity in a dose-dependent manner, which is reversed with the addition of mifepristone (1.25 µM). The fimbrial fallopian tube demonstrated significantly higher HIF-1α staining, particularly in mutation carriers, reflecting a site-specific 'hypoxic niche'. Exposure to hypoxic conditions (1% O) can further impair tumor cytotoxicity in high-risk carriers.
CONCLUSIONS
Phase-specific differential NK cell activity in mutation carriers, either systemically or locally, may favor site-specific pre-invasive carcinogenesis. These cumulative effects across a reproductive lifecycle in high-risk carriers can have a detrimental effect further supporting epidemiological evidence for ovulation inhibition.
PubMed: 38539519
DOI: 10.3390/cancers16061186 -
Contraception: X 2024Document the clinical outcomes of an outpatient medical management with procedural evacuation backup procedure for abortions between 18 weeks zero days to 23 weeks six...
OBJECTIVE
Document the clinical outcomes of an outpatient medical management with procedural evacuation backup procedure for abortions between 18 weeks zero days to 23 weeks six days gestation.
STUDY DESIGN
We conducted a retrospective medical records review of adult patients who received mifepristone and repeated misoprostol for second trimester abortion with procedural evacuation backup at an Arizona clinic between October 2017 and November 2021. We extracted patient demographics; pregnancy and medical history; and preoperative, intraoperative, and postoperative data. We assessed abortion outcomes, including procedure timing, mode of completion (medication alone or medications and procedural evacuation), and safety.
RESULTS
All 359 patients had a complete abortion with 63.5% of patients completing with medication alone and 36.5% with procedural evacuation backup. The median time from first dose of misoprostol to fetal expulsion was six hours, among those who completed the abortion with medications alone. Of those who received procedural evacuation as backup, the median time for procedural evacuation was 10 minutes. The vast majority of patients (99.4%) did not have any adverse events. Two safety incidents (0.6%) occurred, a broad right ligament tear and a uterine rupture.
CONCLUSION
Patients in one outpatient setting safely and effectively received medical management of second trimester abortion with procedural evacuation backup, and two thirds completed with medications alone.
IMPLICATIONS
Outpatient settings may consider medical management of abortion between 18 and 24 weeks with procedural evacuation back-up as a safe, effective, and manageable second trimester abortion option. Additional research is needed on patient experience and satisfaction.
PubMed: 38515629
DOI: 10.1016/j.conx.2024.100104 -
Contraception Jun 2024In November 2022, the anti-abortion advocacy group Alliance for Hippocratic Medicine filed a lawsuit against the U.S. Food and Drug Administration challenging the...
OBJECTIVES
In November 2022, the anti-abortion advocacy group Alliance for Hippocratic Medicine filed a lawsuit against the U.S. Food and Drug Administration challenging the initial 2000 approval of mifepristone and its subsequent approvals, which removed unnecessary restrictions on its use, by disputing the medication's safety record. Such challenges relied on a study examining the incidence of emergency room visits following medication abortion with mifepristone and procedural abortion using Medicaid claims data from 1999-2015. In February 2024 that study was retracted by its publisher. In this paper, we analyzed the methods and presentations of the data used in the study.
STUDY DESIGN
We drew upon commonly accepted principles in responsible epidemiologic and scientific research to evaluate the methods and presentations of the data and organized our findings into themes.
RESULTS
We found multiple instances of methodological flaws, mischaracterizations, and obfuscations of data in this study, including use of a misleading research question and framing, analytic flaws, inappropriate use of an unvalidated proxy measure for outcomes of interest, and inappropriate and deceptive visualizations of data. In each instance, the resulting effect obfuscated and misrepresented the safety of medication abortion with mifepristone.
CONCLUSIONS
The misrepresentation and exaggeration of data promoted and exacerbated misinterpretations about the study's findings, resulting in substantial harm before it was retracted. Recognizing that ongoing judicial proceedings threaten access to conventional reproductive health care in the United States, public health policies must be informed by scientific and medical literature that is comprehensive, methodologically sound, and absent any obfuscations or misrepresentations.
IMPLICATIONS
Studnicki et al.'s study of emergency room visits after abortion misrepresented the safety of mifepristone with multiple instances of methodological flaws and obfuscations of data. While the study has now been retracted, it led to irrevocable harm, threatening access to medication abortion, which has an established safety record.
Topics: Humans; Female; Mifepristone; Abortion, Induced; Pregnancy; United States; Longitudinal Studies; Emergency Service, Hospital; Medicaid; United States Food and Drug Administration; Retraction of Publication as Topic; Abortifacient Agents
PubMed: 38494149
DOI: 10.1016/j.contraception.2024.110417 -
G3 (Bethesda, Md.) May 2024Robust genetic systems to control the expression of transgenes in a spatial and temporal manner are a valuable asset for researchers. The GeneSwitch system induced by...
Robust genetic systems to control the expression of transgenes in a spatial and temporal manner are a valuable asset for researchers. The GeneSwitch system induced by the drug RU486 has gained widespread use in the Drosophila community. However, some concerns were raised as negative effects were seen depending on the stock, transgene, stage, and tissue under study. Here, we characterized the adverse effects triggered by activating the GeneSwitch system in adult muscles using the MHC-GS-GAL4 driver. When a control, mock UAS-RNAi transgene was induced by feeding adult flies with RU486, we found that the overall muscle structure, including myofibrils and mitochondrial shape, was significantly disrupted and led to a significant reduction in the lifespan. Remarkably, lifespan was even shorter when 2 copies of the driver were used even without the mock UAS-RNAi transgene. Thus, researchers should be cautious when interpreting the results given the adverse effects we found when inducing RU486-dependent MHC-GS-GAL4 in adult muscles. To account for the impact of these effects we recommend adjusting the dose of RU486, setting up additional control groups, such as a mock UAS-RNAi transgene, as comparing the phenotypes between RU486-treated and untreated animals could be insufficient.
Topics: Animals; Mifepristone; Transgenes; Muscles; Drosophila Proteins; Animals, Genetically Modified; RNA Interference; Drosophila; Drosophila melanogaster; Phenotype; Longevity
PubMed: 38409337
DOI: 10.1093/g3journal/jkae039