Uso de mifepristona en embarazo ectópico intersticial: un reporte de caso / Use of mifepristone in an interstitial ectopic pregnancy: a case report

Introducción: El embarazo ectópico intersticial es una forma de presentación poco frecuente, con una incidencia del 2-4% de los embarazos ectópicos; sin embargo, a pesar de su baja incidencia la mortalidad es cinco veces mayor, impactando en las cifras de mortalidad materna y representando en torno al 10-15% de los casos. Objetivo: Presentar un caso de embarazo ectópico intersticial, cuya ocurrencia es poco frecuente, así como el abordaje satisfactorio del manejo médico con mifepristona y metotrexato. Caso clínico: Mujer de 28 años con antecedente de resección tubárica por quiste paraovárico derecho, quien acudió a urgencias por hallazgo en ecografía obstétrica de sospecha de embarazo intersticial izquierdo y se le administró manejo farmacológico con dosis de metotrexato y mifepristona, con éxito. Conclusiones: El manejo médico con metotrexato y mifepristona para el embarazo ectópico intersticial parece ser una elección eficaz en los casos con estabilidad hemodinámica y deseo de conservación de la fertilidad.

Background: Interstitial ectopic pregnancy represents a rare form of presentation, with an incidence of 2-4% of all ectopic pregnancies. However, despite its low incidence, it is associated with a five-fold increase in mortality, significantly impacting maternal mortality rates, accounting for approximately 10-15% of cases. Objective: To present a case of interstitial ectopic pregnancy, which is a rare occurrence, as well as the successful medical management approach with mifepristone and methotrexate. Case report: A 28-year-old women with a history of right paraovarian cyst tubal resection presented to the emergency department due to suspected left interstitial pregnancy identified on obstetric ultrasound. The patient was successfully managed with pharmacological treatment using doses of methotrexate and mifepristone. Conclusions: Medical management with methotrexate and mifepristone for interstitial ectopic pregnancy appears to be an effective choice in cases with hemodynamic stability and a desire for fertility preservation.

Analysis of management efficacy in patients with heavy menstrual bleeding associated with antithrombotic therapy / 中华妇产科杂志

Objective: To evaluate different methods' efficacy of controlling acute bleeding and managing long-term menstruation in patients with heavy menstrual bleeding (HMB) associated with antithrombotic therapy. Methods: The clinical data of 22 cases with HMB associated with antithrombotic therapy admitted to Peking University People's Hospital from January 2010 to August 2022 were analyzed, aged 39 years old (26-46 years). Changes in menstrual volume, hemoglobin (Hb), and quality of life were collected after control of acute bleeding and long-term menstrual management. Menstrual volume was assessed by pictorial blood assessment chart (PBAC), and quality of life was assessed by menorrhagia multi-attribute scale (MMAS). Results: (1) Treatment of acute bleeding: of the 22 cases with HMB associated with antithrombotic therapy, 16 cases were treated in our hospital and 6 in other hospital for emergency bleeding; of the 16 cases treated in our hospital, 3 underwent emergency intrauterine Foley catheter balloon compression due to severe bleeding (Hb decreased by 20 to 40 g/L within 12 hours). Of the 22 cases with antithrombotic therapy-related HMB, 15 (including 2 cases with severe bleeding) underwent emergency aspiration or endometrial resection, and intraoperative placement of levonorgestrel-releasing intrauterine system (LNG-IUS) followed by a significant reduction in bleeding volume; 3 cases had controlled acute bleeding after rivaroxaban dose reduction and continued observation; 2 cases were given gonadotropin-releasing hormone agonists to control acute bleeding in other hospital, of which 1 case was temporarily treated with periodic blood transfusion, and the other one patient underwent total hysterectomy; and 2 cases had temporary amenorrhea with oral mifepristone after intrauterine balloon compression or oral norethindrone. (2) Long-term menstrual management: of the 22 cases with antithrombotic therapy-related HMB, 15 had LNG-IUS placement and 12 had LNG-IUS placement for 6 months, and menstrual volume was significantly reduced [PBAC scores were 365.0 (272.5-460.0) vs 25.0 (12.5-37.5), respectively; Z=4.593, P<0.001], Hb was significantly increased [91.5 g/L (71.8-108.2 g/L) vs 128.5 g/L (121.2-142.5 g/L); Z=4.695, P<0.001], and quality of life was significantly improved [MMAS scores were 415.0 (327.5-472.5) vs 580.0 (570.0-580.0), respectively; Z=-3.062, P=0.002] before placement compared with 6 months after placement. Three rivaroxaban dose reduction patients' PBAC scores decreased by 20 to 35 but remained >100, and perceived quality of life did not change significantly. Two cases with temporary amenorrhea treated with oral mifepristone felt significantly improved quality of life, and the MMAS scores increased by 220 and 180, respectively. Conclusion: Intrauterine Foley catheter balloon compression, aspiration or endometrial ablation could be used to control acute bleeding in patients with antithrombotic therapy-related HMB, and LNG-IUS for long-term management could reduce menstrual volume, increase hemoglobin, and improve the quality of life of patients.

Abordaje integral de la Interrupción Voluntaria del Embarazo: (segunda entrega) / Comprehensive approach to the voluntary interruption of pregnancy: (second issue)

La legalización de la interrupción voluntaria del embarazo ha transformado la práctica médica con respecto a la atención de las pacientes que desean interrumpir la gestación hasta la semana 14 en Argentina. En la primera entrega, el equipo PROFAM compartió su punto de vista a través de una adaptación de su material educativo destinado, sobre todo, a aclarar los aspectos legales que hacen a la práctica cotidiana. En esta entrega se desarrolla en detalle el procedimiento para realizar un aborto farmacológico con misoprostol y mifepristona, así como las generalidades del aspirado manual endouterino. (AU)

The legalization of voluntary termination of pregnancy has transformed medical practice regarding the care of patients who wish to terminate a pregnancy up to 14 weeks in Argentina. In the first issue, the PROFAM team shared its point of view through an adaptation of its educational material aimed, above all, at clarifying the legal aspects of daily practice. In this issue, the procedure to perform a pharmacological abortion with misoprostol and mifepristone is developed in detail, as well as the generalities of manual uterine aspiration technique. (AU)

Thunder-fire moxibustion combined with mifepristone for ovarian chocolate cyst dysmenorrhea with kidney deficiency and blood stasis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of thunder-fire moxibustion combined with mifepristone for ovarian chocolate cyst dysmenorrhea with kidney deficiency and blood stasis.@*METHODS@#Seventy patients were randomly divided into an observation group and a control group, 35 cases in each group. The patients in the the control group were treated with oral administration of mifepristone, 10 mg each time, once a day; based on the treatment of the control group, the patients in the observation group were treated with thunder-fire moxibustion at Guanyuan (CV 4), Zigong (EX-CA 1), Xuehai (SP 10), once every other day. Both the groups were treated for 3 months. The Cox menstrual symptom scale (CMSS) score, the maximum cross-sectional area of ectopic cyst, and the serum levels of transforming growth factor-β1 (TGF-β1) and interleukin-17 (IL-17) were observed before and after treatment in the two groups. The clinical efficacy was evaluated.@*RESULTS@#Compared before treatment, the severity scores and duration scores of CMSS as well as the serum levels of TGF-β1 were reduced after treatment in the two groups (@*CONCLUSION@#Thunder-fire moxibustion combined with mifepristone could significantly improve dysmenorrhea symptoms, shorten dysmenorrhea time and promote atrophy of ovarian heterotopic cyst in patients with ovarian chocolate cyst dysmenorrhea of kidney deficiency and blood stasis, and the mechanism may be related to the reduction of serum levels of TGF-β1 and IL-17.

Analysis of the endometrial transcriptome at the time of implantation in women receiving a single post-ovulatory dose of levonorgestrel or mifepristone

Abstract Background: Levonorgestrel (LNG) is a progesterone receptor agonist used in both regular and emergency hormonal contraception; however, its effects on the endometrium as a contraceptive remain widely unknown and under public debate. Objective: To analyze the effects of LNG or mifepristone (MFP), a progesterone receptor antagonist and also known as RU-486, administered at the time of follicle rupture (FR) on endometrial transcriptome during the receptive period of the menstrual cycle. Methods: Ten volunteers ovulatory women were studied during two menstrual cycles, a control cycle and a consecutively treated cycle; in this last case, women were randomly allocated to two groups of 5 women each, receiving one dose of LNG (1.5 mg) or MFP (50 mg) the day of the FR by ultrasound. Endometrial biopsies were taken 6 days after drug administration and prepared for microarray analysis. Results: Genomic functional analysis in the LNG-treated group showed as activated the bio-functions embryo implantation and decidualization, while these bio-functions in the T-MFP group were predicted as inhibited. Conclusions: The administration of LNG as a hormonal emergency contraceptive resulted in an endometrial gene expression profile associated with receptivity. These results agree on the concept that LNG does not affect endometrial receptivity and/or embryo implantation when used as an emergency contraceptive.

Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies

RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation.

Role of antiprogesterone on the endometrium receptivity- a review

Estrogen produces proliferation in the functional layer of the endometrium and the differentiation in the ciliated and secretory epithelium of the uterine tube. Progesterone produces differentiation in the functional layer of the endometrium and the produces mitosis in the stroma of the endometrium. These effects of the estrogen and progesterone are mediated through interactions with specific intracellular receptors1. Mifepristone [RU 486] is a steroid hormone with a chemical structure similar to natural hormone progesterone. It has been proposed that antiprogestins may be useful in the treatment of endometrial inflammatory disease and carcinoma +breast because these conditions are dependent on the ovarian receptors and have receptors for estrogen and progesterone. Anti-progesterone compounds can antagonize the biological action of the progesterone or inhibit the synthesis of progesterone. Mifepristone, [RU 486] has been found to be the most effective and is now used in practice

Therapeutic methods and their effects on patients with cornual pregnancy / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the therapeutic methods and their effects on patients with cornual pregnancies.
@*METHODS@#A retrospective study was performed on 83 patients, who were diagnosed as cornual pregnancy at Drum Tower Hospital from June 2010 to April 2015. The patients were divided into 5 groups: a laparoscope group, angle resection and uterine repair guided by laparoscope (n=16); a surgery group, operated with angle resection and uterine repair (n=49); an abortion group, guided by ultrasound or laparoscope (n=6); a drug group, treated by methotrexate and mifepristone (n=8) and a pregnancy bursal puncture group (n=4). We compared the general conditions, surgery circumstances and average days in hospital among the laparoscope group, the surgery group, and the abortion group. Moreover, we also investigated the outcomes of the drug group and pregnancy bursal puncture group.
@*RESULTS@#Compared with the surgery group, the intraoperative blood loss in the laparoscope group and abortion group was less (P0.05). The length of procedure in the abortion group was less than that in the laparoscope group or the surgery group (P<0.05). The cure rate was 100%.
@*CONCLUSION@#The therapeutic methods based on patient's condition can improve the curative effect and prognosis in cornual pregnancy, which can keep the integrity of generative organs with less injury. The laparoscope might be a main therapeutic method for cornual pregnancy due to its safety, effectiveness, and minimal invasion.

Clinical analyses of 66 cases of mid-trimester pregnancy termination in women with prior cesarean / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The rate of cesarean delivery has significantly increased in China in the last decade. Women with prior cesarean history tend to have a higher risk of uterine rupture during termination of the pregnancy in mid-trimester than those without such a history. The aim of our study was to evaluate the influences of the potential risk factors on uterine rupture in women with prior cesarean.</p><p><b>METHODS</b>We conducted this retrospective study of women with prior cesarean section, who underwent mid-trimester pregnancy termination between January 2006 and December 2013 in Peking Union Medical College Hospital. The protocol was oral administration of mifepristone and misoprostol for the patients with the gestational ages below 16 weeks or intra-amniotic injection of ethacridine lactate (EL) for those with at least 16 weeks of gestational ages. The thickness of the lower uterine segment (LUS) was measured before the termination of pregnancy. Logistic regression was used to study the risk factors of uterine rupture.</p><p><b>RESULTS</b>The total rate of successful abortion was 93.9% (62/66). Four patients failed in induction, and one of them received curettage, whereas the other three experienced uterine rupture (4.5%). The successful rates of abortion were 85.7% (30/35) for women treated with mifepristone-misoprostol and 86.1% (31/36) for those treated with EL. There was a significant difference in the mean LUS thickness between the uterine rupture group (3.0 ± 2.0 mm) and the nonrupture group (7.0 ± 3.0 mm) (P < 0.05). The LUS thickness of <3 mm was associated with uterine rupture during mid-trimester pregnancy termination in women with prior cesarean (odds ratio, 94.0; 95% confidence interval 4.2-2106.1) after adjusted maternal age, gestational age, interdelivery interval and prior cesarean section. Severe bleeding that required transfusion occurred in one case (1.5%).</p><p><b>CONCLUSIONS</b>Both the mifepristone-misoprostol and the EL regimens were effective and safe for the termination of mid-trimester pregnancy in women with prior cesarean. A thinner LUS is associated with a relatively high risk of uterine rupture.</p>

Effect of acupuncture on CXCL8 receptors in rats suffering from embryo implantation failure / 华中科技大学学报（医学）（英德文版）

To observe the effect of acupuncture on CXCL8 receptors (CXCR1 and CXCR2) in rat endometrium experiencing embryo implantation failure, 72 pregnant rats were randomly divided into four groups: normal group (N), embryo implantation failure group (M), acupuncture treatment group (A), and progestin treatment group (W). Then the rats in each group were equally randomized into a day-6 (D6) group, a day-8 (D8) group, and a day-10 (D10) group. The rats in group M, group A, and group W were treated with mifepristone-sesame oil solution on day 1, while the rats in group N were injected with the same amount of sesame oil. Meanwhile, "Housanli" and "Sanyinjiao" were selected for acupuncture. From day 1 to the time of death, the rats in group A were fastened up and then acupuncture was administered while the rats in group N and group M were only fixed, and the rats in group W were given progestin. The number of implanted embryos was calculated. The expression of CXCR1 and CXCR2 in rat endometrium was detected by immunohistochemistry, Western blotting and real-time PCR. Compared to group N, the average number of implanted embryos, the protein and mRNA expression of CXCR1 (D6, D8 and D10), and the protein and mRNA expression of CXCR2 (D8 and D10) in rat endometrium were significantly decreased in group M. Compared to group M, there was significant elevation in the average number of implanted embryos, the protein expression (D6, D8 and D10) and mRNA expression (D8) of CXCR1 in rat endometrium of group A, and the protein expression (D8 and D10) and mRNA expression (D8) of CXCR2 in rat endometrium of group W. These findings indicated that acupuncture can increase the number of implanted embryos in rats of embryo implantation failure, which may be relevant with up-regulation the expression of CXCR1 and CXCR2 at maternal-fetal interface of rats with embryo implantation failure.

Dexamethasone Inhibits Interleukin-1beta-Induced Matrix Metalloproteinase-9 Expression in Cochlear Cells

OBJECTIVES: To investigate the effect of interleukin (IL)-1beta on matrix metalloproteinase (MMP)-9 expression in cochlea and regulation of IL-1beta-mediated MMP-9 expression by dexamethasone and the molecular and signaling mechanisms involved. METHODS: House ear institute-organ of Corti 1 (HEI-OC1) cells were used and exposed to IL-1beta with/without dexamethasone. Glucocorticoid receptor antagonist, RU486, was used to see the role of dexamethasone. PD98059 (an extracellular signal-regulated kinases [ERKs] inhibitor), SB203580 (a p38 mitogen-activated protein kinases [MAPK] inhibitor), SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor) were also used to see the role of MAPKs signaling pathway(s) in IL-1beta-induced MMP-9 expression in HEI-OC1 cells. Reverse transcription-polymerase chain reaction and gelatin zymography were used to measure mRNA expression level of MMP-9 and activity of MMP-9, respectively. RESULTS: Treatment with IL-1beta-induced the expression of MMP-9 in a dose- and time-dependent manner. IL-1beta (1 ng/mL)-induced MMP-9 expression was inhibited by dexamethasone. Interestingly, p38 MAPK inhibitor, SB203580, significantly inhibited IL-1beta-induced MMP-9 mRNA and MMP-9 activity. However, inhibition of JNKs and ERKs had no effect on the IL-1beta-induced MMP-9 expression. CONCLUSION: These results suggest that the pro-inflammatory cytokine IL-1beta strongly induces MMP-9 expression via activation of p38 MAPK signaling pathway in HEI-OC1 cells and the induction was inhibited by dexamethasone.

Mifepristone repairs alteration of learning and memory abilities in rat model of depression / 药学学报

This study is to investigate the amelioration effect of glucocorticoid receptor (GR) antagonist mifepristone on the changes of learning and memory abilities in rat model of depression. In the present study, a 35-day rat chronic unpredictable stress (CUS) model was used to observe both depression-like behaviors with sucrose preference test and open-field test and learning and memory-associated behaviors with Morris water maze test. A total of 45 male adult Sprague-Dawley rats were randomly assigned to three groups of equal size: control group (CON); CUS group (CUS); CUS + mifepristone group (CM). Animals in CM group were first exposed to CUS for 14 days, and then were administered with 50 mg x kg(-1) x d(-1) of mifepristone with continued CUS procedure. Corticosterone EIA Kit was used to detect the concentration of plasma corticosterone (CORT). Nissl staining was used to observe the structure of hippocampus. The results demonstrated that CUS exposure induced both depressive-like and learning and memory-associated behaviors and these deficits were reversed by mifepristone. Compared to CON group, the concentration of plasma CORT increased significantly in CUS group. CUS exposure damaged the structure of hippocampus, whereas mifepristone had an amelioration effect. Together, the structural deficits of hippocampus resulting from long-term stress exposure, which could contribute to the impairment of learning and memory in depression, are reversed by the GR receptor antagonist mifepristone.

The effects of Nrf2 gene expression induced by RU486 at different doses on A549 cell damage induced by paraquat / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the effects of Nrf2 gene expression induced by RU486 at different doses on A549 cell damage induced by paraquat (PQ).</p><p><b>METHODS</b>After A549 cells transfected with Ad-RUNrf2 were treated by RU486 at the doses of 10(-10), 10(-9), 10(-8) and 10(-7) mol/L for 6 h, A549 cell cultures were exposed to 10(-3) mol/L of PQ for 48 h. Then qRT-PCR and EMSA assays were used to detect the expression of Nrf2 gene, and qRT-PCR and ELISA assays were utilized to measure the effects of Nrf2 gene on the expression of the inflammatory cytokines IL-6, IL-10 and TNF-α, apoptotic factors Caspase-3, Caspase-9 and Cytochrome C. The oxidation factors (CAT and MDA protein contents) were observed by Chemical Colorimetric Analysis.</p><p><b>RESULTS</b>Nrf2 gene relative expression and protein contents increased with RU486 concentrations, and the above expression was the highest when the concentration of RU486 was 10(-7) mol/L, which was significantly higher than those in control and PQ exposure groups (P < 0.01 or P < 0.05). The relative gene expression and protein expression of IL-6 and TNF-α enhanced with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05), while the change of IL-10 content was the opposite. The relative expression of Caspase3, Caspase9 and Cytochrome C genes also increased with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05). The content of CAT enhanced with RU486 concentration, which was the highest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.05). But the change of MDA content was the contrary.</p><p><b>CONCLUSION</b>Nrf2 expression induced by RU486 can promote the balance of oxidation-antioxidation system in A549 cells and inhibit the inflammation and apoptosis factors, which has a protective effect on A549 cell injury induced by PQ.</p>

Determinations of mifepristone and its metabolites and their pharmacokinetics in healthy female Chinese subjects / 药学学报

The aim of this study is to establish an HPLC method for simultaneous determinations of mifepristone and its metabolites, mono-demethylated mifepristone, di-demethylated mifepristone and C-hydroxylated mifepristone in plasma and to evaluate the pharmacokinetic characteristics of mifepristone tablet. Twenty healthy female Chinese subjects were recruited and a series of blood samples were collected before and after 0.25, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 12.0, 24.0, 48.0, 72.0 and 96.0 hours administration by a single oral dose of 75 mg mifepristone tablet. Mifepristone and its three metabolites were extracted from plasma using ethyl acetate and determined by high performance liquid chromatography. The main pharmacokinetic parameters of mifepristone and its metabolites, including Cmax, tmax, MRT, t(1/2), V, CL, AUC(0-96 h) and AUC(0-infinity), were calculated by Drug and Statistical Software Version 2.0. The simple, accurate and stable method allows the sensitive determinations of mifepristone and its metabolites in human plasma up to 4 days after oral administration of 75 mg mifepristone tablet and the clinical applications of their pharmacokinetic studies.

Therapeutic effect of pelvic methotrexate injection via the posterior fornix for treatment of tubal pregnancy / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect and safety of pelvic methotrexate (MTX) injection via the posterior fornix for treatment of tubal pregnancy.</p><p><b>METHODS</b>Ninety-six patients with tubal pregnancy (mean age 21-40 years) were randomized into 3 groups for treatment with pelvic MTX injection via the posterior fornix+mifepristone+traditional Chinese medicine (experiment group), intramuscular MTX injection+mifepristone+traditional Chinese medicine (control group I), or mifepristone+traditional Chinese medicine (control group II). On days 4 and 7 of the treatment, blood β-HCG of the patients in different groups was detected, and in cases with continuous reduction of blood β-HCG or a reduction by over 15%, β-HCG was checked every week. One week after the treatment, the size of the mass was measured by B-mode ultrasound. The clearance time of β-HCG and the hospital stay of the patients were recorded.</p><p><b>RESULTS</b>Twenty-nine patients in the experimental group were treated successfully, with a cure rate of 90.6%, which was significantly higher than those in the two control groups (P<0.05). The clearance time of β-HCG and hospital stay were also much shorter in the experimental group (P<0.05).</p><p><b>CONCLUSION</b>Pelvic MTX injection via the posterior fornix is a convenient procedure associated with minimal complications and serves as a good alternative for treatment of tubal pregnancy.</p>

Direct Corticosteroid Modulation of GABAergic Neurons in the Anterior Hypothalamic Area of GAD65-eGFP Mice

Corticosterone is known to modulate GABAergic synaptic transmission in the hypothalamic paraventricular nucleus. However, the underlying receptor mechanisms are largely unknown. In the anterior hypothalamic area (AHA), the sympathoinhibitory center that project GABAergic neurons onto the PVN, we examined the expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) of GABAergic neurons using intact GAD65-eGFP transgenic mice, and the effects of corticosterone on the burst firing using adrenalectomized transgenic mice. GR or MR immunoreactivity was detected from the subpopulations of GABAergic neurons in the AHA. The AHA GABAergic neurons expressed mRNA of GR (42%), MR (38%) or both (8%). In addition, in brain slices incubated with corticosterone together with RU486 (MR-dominant group), the proportion of neurons showing a burst firing pattern was significantly higher than those in the slices incubated with vehicle, corticosterone, or corticosterone with spironolactone (GR-dominant group; 64 vs. 11~14%, p<0.01 by chi2-test). Taken together, the results show that the corticosteroid receptors are expressed on the GABAergic neurons in the AHA, and can mediate the corticosteroid-induced plasticity in the firing pattern of these neurons. This study newly provides the experimental evidence for the direct glucocorticoid modulation of GABAergic neurons in the AHA in the vicinity of the PVN.

Expression and regulation of Enpp2 in rat uterus during the estrous cycle

Ectonucleotide pyrophosphatase/phosphodiestrase 2 (Enpp2) isolated from the supernatant of human melanoma cells is a lysophospholipase D that transforms lysophosphatidylcholine into lysophospatidic acid. Although multiple analyses have investigated the function of Enpp2 in the hypothalamus, its role in the uterus during the estrous cycle is not well understood. In the present study, rat uterine Enpp2 was analyzed by RT-PCR, Western blotting, and immunohistochemistry. Quantitative PCR analysis demonstrated that uterine Enpp2 mRNA was decreased during estrus compared to proestrus and diestrus. To determine whether uterine Enpp2 expression is affected by sex steroid hormones, immature rats were treated with 17beta-estradiol (E2), progesterone, or both on postnatal days 14 to 16. Interestingly, the expression of Enpp2 mRNA and protein were down-regulated by E2 in the uterus during estrus but not during proestrus or diestrus, suggesting that Enpp2 may play a role in uterine function during estrus. Enpp2 is primarily localized in the stromal cells of the endometrium during proestrus and estrus. During diestrus, Enpp2 was highly expressed in the epithelial cells of the endometrium. Taken together, these results suggest that uterine Enpp2 may be regulated by E2 and plays a role in reproductive functions during female rat development.

Mifepristona para tratamiento del fibroma uterino / The use of Mifepristone for treatment of the uterine fibroma

OBJETIVOS: Evaluar la eficacia, seguridad y duración de la mejoría clínica en el tiempo de la administración de 5 vs. 10 mg diarios de mifepristona en el tratamiento del fibroma. MÉTODOS: Fueron aleatorizadas a recibir 5 ó 10 mg diarios de mifepristona oral durante 3 meses y fueron seguidas durante 6 meses después, 100 mujeres con fibromatosis uterina sintomática. Se calcularon los volúmenes del fibroma y del útero por ultrasonografÍa abdominal del útero al inicio, al final del tratamiento, 3 y 6 meses después. RESULTADOS: Al final del tratamiento el fibroma se redujo en 38,3 por ciento, p < 0,001, y 47,5 por ciento, p < 0,001, respecto del valor inicial en los grupos de 5 y 10 mg, respectivamente. El volumen del útero se redujo el 27 por ciento (p = 0,001) y 25,1 por ciento (p = 0,001), con respecto al inicio en los grupos de 5 y 10 mg, respectivamente. La prevalencia de los síntomas fue significativamente menor al final de tratamiento y 6 meses después. Seis meses después del tratamiento el tamaño del fibroma era 21, por ciento y 19, por ciento menor que el valor inicial en los grupos de 5 y 10 mg de mifepristona, respectivamente, y el volumen del útero era 2 por ciento y 0,2, por ciento menor que al inicio en los grupos de 5 y 10 mg, respectivamente. No hubo hiperplasia endometrial en ninguno de los grupos de tratamiento. CONCLUSIONES: La dosis de 5 mg tuvo similar eficacia que la de 10 mg y 6 meses después de concluido el tratamiento los tamaños del fibroma y del útero estaban cercanos a los valores pretratamiento, pero se mantenía una notable mejoría clínica

OBJECTIVES: to evaluate the efficacy, safety and duration improvement obtained over the course of time by administering mifepristone for the treatment of fibroids. METHODS: One hundred women with symptomatic uterine myomas were randomized to receive oral mifepristone 5 or 10 mg daily for 3 months with 6 month post-treatment monitoring. The fibroid and uterus sizes were calculated by means of abdominal ultrasound examination at the beginning and at the end of treatment as well as 3 and 6 months later. RESULTS: At the end of treatment the fibroid decreased in size 38.3 por ciento, p < 0.001, and 47.5 por ciento, p < 0.001, respecting to the initial value in the 5 and 10 mg groups, respectively. The uterine volume decreased 27 por ciento (p = 0.001) and 25.1 por ciento (p = 0.001), regarding to initial values in the 5 and 10 mg groups, respectively. Symptom prevalence was significantly less at the end of treatment and 6 months later. Six months after treatment fibroid size was 21 por ciento and 19 por ciento less than the initial value in the 5 and 10 mg mifepristone groups, respectively, and uterine volume was 2 por ciento and 0.2 por ciento less than initial values in the 5 and 10 mg groups, respectively. There was no endometrial hyperplasia in any of the treatment groups. CONCLUSIONS: The 5 mg dose had an efficacy similar to the 10 mg dosage and 6 months after termination of the treatment fibroid and uterine sizes were close to pre-treatment values but a notable clinical improvement was maintained