Clinical Research on Efficacy of Cassia Twig Tuckahoe Capsule and Mifepristone Combined with Laparoscopic Surgery for the Treatment of Endometriosis

Objective: To compare the clinical efficacy of Cassia Twig Tuckahoe capsule (Chinese Medicine) and Mifepristone combined with laparoscopic surgery for the treatment of endometriosis. Designs: Prospective cohort study. Setting: Gynecology and Obstetrics Department, Jingzhou Central Hospital, affiliated to Yangtze University. Methods: We selected 67 patients suspected with endometriosis and divided randomly into 2 groups on patient choice. Outcome Measures: Treatment efficacy, side effects, recurrence rate and pregnancy rate. Results: Comparing the effect of treatment between the two groups, the success rate was almost same (P > 0.5). However, the disappearance of pain was faster in Cassia twig Tuckahoe group (P Conclusion: After analysis of the result, Cassia twig Tuckahoe capsule combined with Laparoscopy is superior to the Mifepristone combined with Laparoscopy. Cassia twig Tuckahoe capsule is a very propitious medicine for treating endometriosis for long term benefits.

Effect of Mifepristone on the Telomerase Activity in Chorion and Decidua during Early Pregnancy

Objective To investigate telomerase activity in chorion and decidua from abortion induced by mifepristone incorporated with misoprostol at early pregnancy. Methods TRAP-SYBR Green assay was used to detect the expression of telomerase. Forty specimen were obtained from medicinal abortion （experiment group） and forty were from normal induced abortion （control group）. Results Positive expression of chorion telomerase was significantly different between the experimental group （28%, 11/40） and the control group （73%, 29/40） （P〈0.05）. While in decidua, the positive rate was 28% （11/40） in the experimental group and 20% （9/40） in the control group, there was no significant difference （P〉0.05）. Conclusion It is suggested that miferistone may significantly decrease the telomerase activity in chorion but not in decidua.

Clinical Observation on Termination of Early Pregnancy of 213 Cases after Caesarian Section with Repeated Use of Mifepristone and Misoprostol

Objective To investigate the efficacy and safety in women after caesarian section for termination of early pregnancies by treatment, or repeated treatment with mifepristone and misoprostol. Subjects and Methods A total of 213 pregnant women with amenorrhea of 34~69 d after caesarian section who asked for medical abortion were recruited, including 63 cases undergoing their second medical abortion. A total amount of mifeprisstone of 150 mg given in separate doses (25 mg×4 and 50 mg at the first time) was administered orally within 3 d, followed by misoprostol of 0.6 mg orally in the morning of d 3. Results The complete abortion rate was 92.5%, incomplete abortion was 4.7% and failure was 2.8%. Conclusion The sequential use of mifepristone and misoprostol could be successfully and repeatedly used for induced abortion in those women with a caesarian section history. Its efficacy was similar to that for ordinary population. Its safety and effectiveness were satisfactory.

REVERSAL EFFECTS OF MIFEPRISTONE ON MULTIDRUG RESISTANCE(MDR) IN DRUG-RESISTANT BREAST CANCER CELL LINE MCF7/ADR IN VITRO AND IN VIVO

To explore the reversal effect of mifepristone on multidrug resistance (MDR) in drug-resistant human breast cancer cell line MCF7/ADR and its mechanisms. Methods: Expression of MDR1 and MDR-associated protein(MRP) mRNA in MCF7/ADR cells was detected using reverse transcription- polymerase chain reaction(RT-PCR). Western blotting was used to assay the protein levels of P-glycoprotein (P-gp) and MRP. Intracellular rhodamine 123 retention and [3H]vincristine (VCR) accumulation were measured by flow cytometry and liquid scintillation counter, respectively. MTT reduction assay was used to determine the sensitivity of cells to the anticancer agent, adriamycin (ADR). Additionally, a MCF7/ADR cell xenograft model was established to assess the reversal effect of mifeprisone on MDR in MCF7/ADR cells in vivo. Results: Miferpristone dose-dependently down- regulated the expression of MDR1 and MRP mRNA in MCF7/ADR cells, accompanied by a significant decrease in the protein levels of P-gp and MRP. After exposure to 5, 10, and 20 mmol/L mifepristone, MCF7/ADR cells showed a 3.87-, 5.81-, and 7.40-fold increase in the accumulation of intracellular VCR(a known substrate of MRP), and a 2.14-, 4.39-, and 5.53-fold increase in the retention of intracellular rhodamine 123(an indicator of P-gp function), respectively. MTT analysis showed that the sensitivity of MCF7/ADR cells to ADR was enhanced by 7.23-, 13.62-, and 20.96-fold after incubation with mifepristone as above-mentioned doses for 96 h. In vivo, mifepristone effectively restored the chemosensitivity of MCF7/ADR cells to ADR. After 8 weeks of administration with ADR(2 mg穔g-1穌-1) alone or in combination with mifepristone(50 mg穔g-1穌-1), the growth inhibitory rate of xenografted tumors in nude mice was 8.08% and 37.25%, respectively. Conclusion: Mifepristone exerts potent reversal effects on MDR in MCF7/ADR cells in vitro and in vivo through down- regulation of MDR1/P-gp and MRP expression and inhibition of P-gp- and MRP-dependent drug efflux, thus increasing the sensitivity to anticancer drug.

Comparative Study on Effects of Arnebia Euchroma (Royle) Johnst Granular and Decoction Forms on Medical AbortionwithMifepristone andMisoprostol

Objective To compare the effects of 2 dosage-forms (granular and decoction) of Arnebia euchroma (royle) Johnst (Arnebia EJ in short below) on medical abortion with that of mifepristone combined with misoprostol Methods Totally 648 women, who had pregnancy of 38-45 d and were willing to terminate pregnancy with mifepristone and misoprostol, were randomly divided into 3 groups, each of which was respectively given granular of Arnebia EJ, placebo granular, or decoction of Arnebia EJ besides mifepristone and misoprostol. The abortion results, bleeding duration, menstruation recovery and side-effects were observed. Results Neither complete abortion rates nor average bleeding durations of the granular group and the decoction group were significantly different (P>0.05). The complete abortion rate and bleeding duration of the two groups were respectively higher and shorter than those of the placebo group (P<0.05). However, the menstruation recov- ery was not significantly different among the three groups (P>0.05). The decoction of Arnebia EJ caused significantly more nausea and vomiting than the other groups (P<0.05). Conclusion The granular form did not have the odor of Arnebia EJ, and caused much less nausea and vomiting compared with the decoction form. The granular and decoc- tion forms were equally effective in improving the results of medical abortion. There- fore it is necessary to conduct further studies on the granular form of Arnebia EJ.

Low doses of domestic mifepristone for emergency postcoital contraception: a preliminary clinical result in Shanghai

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Mifepristone modulates serotonin transporter function

Regulating serotonin expression can be used to treat psychotic depression. Mifepristone, a glu- cocorticoid receptor antagonist, is an effective candidate for psychotic depression treatment. However, the underlying mechanism related to serotonin transporter expression is poorly un- derstood. In this study, we cloned the human brain serotonin transporter into Xenopus oocytes, to establish an in vitro expression system. Two-electrode voltage clamp recordings were used to detect serotonin transporter activity. Our results show that mifepristone attenuates serotonin transporter activity by directly inhibiting the serotonin transporter, and suggests that the se- rotonin transporter is a pharmacological target of mifepristone for the treatment of psychotic depression.

EFFECT OF MIFEPRISTONE (RU486)ON MARKERS OF ENDOMETRIAL RECEPTIVITY

Objective To study the effect of single and low dose of RU486 on endometrial receptivity of healthy women. Methods A total of 5 healthy women were followed for one control and one treatment cycle. In the treatment cycle, a dose of 10 mg RU486 was administered on day luteinizing hormone (LH)-2. In both the control and treatment cycle, an endometrial biopsy was obtained on LH+7. These biopsies were assessed by immunohistochemical analysis to find the difference in expression of integrins and progesterone receptor (PR) between the control and treatment cycle. Results The treatment with RU486 increased the expression of α 1 and α 4 subunits of integrin in glandular epithelial cells, but did not influence β 3 subunit. Moreover, the normal down regulation of PR in epitherial cell nuclei was inhibited by 10 mg RU486. Conclusion Single dose of 10 mg RU486 impairs the establishment of endometrial receptivity on time.

Effects of Mifepristone (RU486) on Development and Ultrastructure of Mouse Blastocysts

Objective To investigate effects of mifepristone （MP） on the development and ultrastructure of mouse blastocysts in vivo Methods Sixty female mice were equally divided into 4 groups： control group （group A）, 1.9 mg/kg MP group （group B）, 5.6 mg/kg MP group （group C）, and 16.8 mg/kg MP group （group D）. The female mice of 4 groups undertook a superovulation method. The development of obtained blastocysts was evaluated, and ultrastructural changes of the blastocysts were observed by transmission electron microscope. Results In comparison with group A, the development rate of blastocysts in group B showed no difference （P〉0.05）, while the development rate of blastocysts in both group C and group D was significantly lower （P〈0.05）. With doses of 5.6 mg/kg and 16.8 mg/kg, the blastocysts showed granular appearance of the cytoplasm, irregular cell borders, enlarged perivitelline space and degeneration. Ultrastructure of the blastocysts in group B was similar to group A, except a little number of fat droplets in the cytoplasm. In group C, the microvilli on apical surface was decreased in number or even disappeared, mitochondria were under developed, a lot of filamentous crystals were found in the cytoplasm. Cellular junctions were defected. In group D, the blastocyst cells were irregular in shape, mitochondria were frequently vacuolated, the nucleolus was enlarged, nuclear membrane was ruptured, and chromatin was slack. Conclusion MP could damage to the ultrastructure of mouse blastocyst, and was responsible for the inhibition of blastocyst development. The inhibitory effect of MP would be in a dose-dependent fashion.

Effects of Mifepristone Compound on the Receptors of Estrogen and Progesterone in Early Pregnancy Deciduas

To examine the effect of mifepristone compound (mifepristone + anor- drin) on estrogen receptor (ER) and progesterone receptor (PR) in early pregnancy decidua. Materials & Methods A Controlled study was carried out among 60 normal early pregnant volunteers (≤49d) in the department of obstetric and gynecology of Peking Union Medical Hospital. The concentrations of ER and PR were measured by radio- ligand and were compared with the control subjects after oral administration of mifepristone or mifepristone compound in different doses. Results The concentration of PR decreased while that of ER increased significantly in the decidua from all subjects administrated with mifepristone compound. We also found the concentration of EcR in Group 5 (mifepristone 30 mg + AF-53 5 mg) was the highest among 6 groups. The compound may be in favor of estrogen's action on endometrium. Conclusion The results indicate that mifepristone compound with AF- 53 has a coordi- nated function and can change the proportion of PR and ER. Hence, it can facilitate abortion. The compound dose of mifepristone 30 mg + AF-53 5mg is in favor of the endometrium recovering.

Effect of Mifepristone on Transforming Growth Factor -βand its Receptor Transcription in Decidua, Villi and Serum Tumor Necrosis Factor -α Level in Early Human Gestation

Objective To investigate the role of mifepristone in regulating cytokines of materno-fetal interface and serum of human early gestationMethods Thirty-five women with early pregnancy received mifepristone 50 mg orallyon study d 1 and d 2, respectively, followed by undergoing artificial abortion to getdecidua and villi on study d 3. Twenty-five women with early pregnancy withoutmifepristone administration as control also underwent artificial abortion to get de-cidua and villi. The expressions of TGF-β1 and TGF-β1 receptor mRNA in the earlydecidua and villi were assessed by using RT-PCR . The concentrations of serum TNF-α were measured by radioimmunoassay.Results The decidual expressions of TGF- β1 mRNA and TGF-β1 receptor mRNA in thetreated group were significantly lower than those of the control (P<0.05), while thevillus expressions of TGF-β1 and TGF-β1 receptor mRNA in the treated group were notsignificantly different from those of the control (P>0.05). The serum TNF-β1 levelselevated significantly after mifepristone treatment.Conclusion The antigestational effect of mifepristone might act through suppressingthe transcription of TGF-β1 and TGF-β1 receptor in the decidua and increasing theserum TNF-α level, which interfered in the materno-fetal interface Th2 bias.

A randomized double-blind multicenter study on comparing levonorgestrel and mifepristone for emergency contraception

Objective: To compare the efficacy and side effects of levonorgestrel and low dose mifepristone in emergency contraception. Method: The study is a randomized double--blind multicenter comparative trial. A total of 1, 276 women with unprotected intercourse within 72 hours were allocated to one of the two study groups. In the levonorgestrel (LNG) group, 0. 75 mg LNG was taken twice, 12 hours apart, whereas in the mifepristone (Mife) group, a single dose of 10 mg mifepristone was taken and a placebo 12 hours after. Follow--up visit was paid on the seventh day of the expected next menstruation to evaluate the contraceptive efficacy and side effects. Contraceptive efficacy was calculated by Dixon’s method. Result:In the LNG group 20 pregnancies occurred among 643 women, while in the Mife group 9 pregnancies occurred among 633 women. The pregnancy rates were 3. 10% and 1. 43% respectively. Contraceptive efficacy rate of preventing pregnancy was 59. 16% and 79. 73%, the difference was statistically significant (P<O. 05). The incidence of various side effects, which were mild, was less than 10%. There was no statistical difference between the two groups. The percentage of subjects who had their next menstruation 3 days earlier or later than their expected menstruation in LNG group and Mife group was 77. 7% and 78. 5% respectively. Conclusion: Use of levonorgestrel or low dose mifepristone for emergency contraception is effective and safe.

Mifepristone in Combination with Misoprostol vs. Low Dose Mifepristone Alone in Emergency Contraception: a Multi-center Double-blind Randomized Clinical Trial

To compare the effectiveness and side effects of various low dose of Mifepristone in combination with Misoprostol and low doses Mifepristone alone in emergency contraception Materials & Methods This is a multi center double blind randomized controlled clinical trial. A total of 899 healthy women were allocated into this study and were randomly divided into 3 groups. They were orally administrated with different emergency contraceptives with 120 h after unprotected intercourse. Group I (n=300) was given 25 mg Mifepristone plus 0.2 mg Misoprostol after 24 h. Group II (n=299) was given 10 mg Mifepristone plus 0.2 mg Misoprostol after 24 h. Group III (n=300) was administrated with 10 mg Mifepristone alone. The effective rates in different groups were calculated with Dixon method. Results Altogether 11 pregnancies occurred, among which 2 cases were in Group I, 2 cases in Group II, and 7 cases were in Group III. After correction with method failure, there was only one case in Group I, 0 case in Group II, and 5 cases in Group III. The contraceptive effectiveness in these groups was 95.5%, 100% and 76.9% respectively. The pregnancy rate was significantly lower in Group I and Group II than that of Group III (P<0.01). The side effects were slight and tolerable, and there was no significant difference between different groups (P>0.05). Conclusion Use of low dose Mifepristone (25 mg or 10 mg) in combination with 0.2 mg Misoprostol was an effective, low side effects and safe treatment regimen for emergency contraception.

Effects of a Single and Low Dose of Mifepristone on Integrin Expression in Human Endometrium During the Peri-implantation Period

Objective In order to gain further information about the mechanism of emergency contraception, during the peri-implantation period the effect of single and low dose of Mifepristone on the expression of integrin level in endometrium of healthy women were observed Materials ＆ Methods Eleven healthy women, proven fertility, were randomly divided into two groups: group LH-2 (n = 5) and LH+ 2 (n = 6). During the control and treatment cycle, placebo or 10 mg Mifepristone were given orally to group LH- 2 on cycle day LH- 2 or to group LH + 2 on cycle day LH - 2, respectively. One endometrial tissue specimen was obtained in both the control and the treatment cycle on cycle day LH+ 7.In this study, the endometrial specimens were assessed by immunohistochemistry analysis to measure the change of integrin α1, α4 and β3 subunits expression on the endometrium after using Mifepristone.Results Mifepristone increased the expression of α1 and α4 subunit in glandular epithelium only in group LH- 2. The expression of β3 integrin subunit remain the same in our experiments.Conclusion Treatment with Mifepristone interferes with integrin distribution during the implantation period, which may imply that the contraceptive effect of Mi fepristone is primarily due to impaired endometrial receptivity.

The Clinical Study on Effect of a Combination of Mifepristone with Misoprostol on Late Luteal Fertility Regulation

Objective To investigate the efficacy, safety and acceptability of mifepristone combined with misoprostol used for late luteal fertility regulationMaterials & Methods Sixty-one female volunteers were recruited and there were 261 treatment cycles in total. Subjects were planned to receive treatment with 25 mg of mifepristone, Q12 h × 4 orally for five days prior to expected menstruation followed by 400 μg of misoprostol 48 h later for up to six cycles.Results There were 13 pregnancies in the 267 treatment cycles and among them complete abortion and continuing pregnancy occurred in 7 and 6 cycles respectively. So the overall pregnancy rate was 4. 87% (13/267) and the rate of continuing pregnancy was 2. 25% (6/267) , while the failure rate per pregnant cycle was 46. 15% (6/13). In treatment cycles the vaginal bleeding patterns changed insignificantly as compared with those in control cycles.Conclusion The efficacy, compliance and acceptability of the regimen should be further improved when it was administered for late luteal fertility regulation.

Effect of Mifepristone and Anordrin Compound on Levels of Estrogen and Progesterone Receptor mRNAs in Human Decidua of Early Pregnancy

To provide the theoretical fundation for the further clinical application of mifepristone and anordrin compound. Materials & Methods Ribonuclease protection assay was used for the detection and quantitation of estrogen and progesterone receptor mRNAs in human decidua from the termination of early pregnancy.Three groups, each of which had 6～8 cases, were studied. Results Compared to the normal control group, estrogen and progesterone receptor mRNAs increased significantly (P<0.05) in the mifepristone group, whereas the changes in the group administrated mifepristone compound which contains anordrin were not obvious. Conclusions The result suggests that with the similar clinical effect, mifepristone compound has less side effect on the patients, thus being more suitable for the anti early pregnancy drug.

Clinical Effects of Lithospermum Ruderale Dosage and Using-time on Medicinal Abortion Induced by Mifepristone and Misoprostol

The clinical effects of dosage during the period of treatment of Lithospermum Ruderale extract-a kind of Chinese traditional herbal medicine-on medicinal abortion induced by mifepristone and misoprostol were studied. Lithospermum Ruderale extract was administrated 3 d before, 3 d after or 3 d before plus 3 d after the administration of misoprostol respectively. The dose of Lithospermum Ruderale extract was 50 g, 75 g or 100 g respectively. Thus 1 350 women of early pregnancy were grouped into 9 groups and observed. The results showed that the effects of Lithospermum Ruderale used 3 d before, and 3 d before plus 3 d after (6 days misoprostol were significantly better than those only used 3 d after misoprostol both for complete abortion and bleeding (P<0.05). The dosage between 50 g and 100 g made no significant difference in clinical effects. Therefore it is reasonable to use 50 g Lithospermum Ruderale before misoprostol to improve medicinal abortion.

A prospective randomized, placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy

A prospective randomized, placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy. Author: Dr Roopa Malik, Assistant Professor, Obstetrics and gynaecology department Pt BDS PGIMS Rohtak BACKGROUND: Vaginal misoprostol has been shown to be an effective single agent for medical agent for medical abortion. This randomized, placebo controlled trial compared a regimen of mefipristone and misoprostol with misoprostol alone for termination of early pregnancy. METHODS: 200 women with gestation <56 days were randomized by a random number table to receive either 200 mg mifepristone orally or placebo followed 48 h later by 800 ug vaginal misoprostol. Abortion success was defined as complete abortion without the use of surgical aspiration. RESULTS: Successful medical abortions occurred in 96 out of 100 subjects (96%) after mifepristone followed by vaginal misoprostol. In all, 79 out of 100 subjects (79%) successfully aborted after placebo and vaginal misoprostol. The higher success rate of complete abortion with mifepristone and misoprostol regimen was statistically significant compared with the placebo and misoprostol regimen (p < 0.05). CONCLUSION: A regimen of mifepristone and misoprostol was significantly more effective for termination of pregnancies <56 days than misoprostol alone. The misoprostol alone regimen for termination of early pregnancy is not a very good method for medical abortion but 79% efficacy obtained with vaginal misoprostol alone may clinically acceptable when mifepristone is not available.

Efficacy of Carboprost Tromethamine Combined with Mifepristone in the Treatment of Uterine Fibroids

The objective of this study was to investigate the clinical efficacy of carboprost tromethamine combined with mifepristone in the treatment of uterine fibroids.A total of 66 patients with uterine fibroids admitted to our hospital between April 2018 and January 2019 were selected as subjects.According to the two different treatment methods,patients were divided equally:The observation group and the control group,each group of 33 people.The oxytocin drug treatment was medicated to the control group,and the prostaglandin tromethamine combined with mifepristone was medicated to the observation group.The treatment effect,adverse reaction,operation,and uterine muscle before and after surgery were observed in these two groups:Tumor tissue progesterone receptor and estrogen receptor levels.The clinical treatment effect of the observation group was 93.94%,and the clinical treatment effect of the control group was 60.61%.The clinical treatment effect of the observation group was significantly higher than that of the control group;furthermore,the incidence of adverse reactions in the observation group in terms of rash,fatigue,nausea,and vomiting was much lower than the control group and could observe a significant difference.Finally,in observation group,the amount of intraoperative blood loss,operation time,and hospitalization time was better than those of the control group.The progesterone receptor and estrogen receptor levels in the uterine fibroid tissue after surgery should also be better than the control group,and it is worth to make a further comparison.Carboprost tromethamine combined with mifepristone is effective in the treatment of uterine fibroids and can be further developed.

Clinical Effects of Lithospermum Ruderal on Medical Abortion by Mifepristone

Early pregnancies(<42d)in 600 women were terminated respectively by mifepristone and Lithospermum Ruderal with misoprostol or mifepristone with misoprostol. The results showed that the rate of complete abortion(99.00%)of 300 women by mifepristone and Lithospermum Ruderal with misoprostol was significantly higher than that (92. 33%)of the other 300 women by mifepristone with misoprostol(P<0.01).The average length of time of embryo removal(54.01±7.55 h)and the rate of embryo removal (82.33%)within 6 hours after administration of misoprostol of the former were significantly shorter and higher than those(56.41±9.93 h and 72.67%) of the latter(P<0.05 respectively).The average length of the bleeding time of the former(7.01±3.11d)was significantly shorter than that(8.09±5.63d)of the latter(P<0.05).The recovery of the menstruation of both was not significantly different from each other(P>0.05).In all, the medical abortion by mifepristone and Lithospermum Ruderal with misoprostol was even more successful,with less bleeding time.Therefore it is essential to make researches on the auxiliary effects of Lithospermum Ruderal on the medical abortion by mifepristone with misoprostol.