双炔失碳酯加强米非司酮终止早孕的临床观察

目的:观察双炔失碳酯加强米非司酮对人体抗早孕的作用,以期提高药物流产的成功率,减轻药物流产后出血时间长的副作用。方法: 143例研究对象使用随机数字表法分为对照组72例,常规药物流产;观察组71例,在常规药物流产基础上加用双炔失碳酯7. 5mg,间隔24h, 2次。观察分析两组对象孕囊排出时间、流产后阴道出血情况及尿hCG的变化。结果:与对照组相比,观察组孕囊排出时间及流产后出血时间均明显缩短(P<0. 01 ),药流后出血时间≤14天者明显增加(P<0. 01 ), >21天者明显减少(P<0. 01 ),流产后两周尿hCG阳性率明显降低(P<0. 05);观察组完全流产率高于对照组,但无统计学差异(P>0. 05)。结论:在常规流产药物的基础上加用小剂量双炔失碳酯可以加强米非司酮的抗早孕作用,缩短药物流产后出血时间,提高药物流产的安全性。     

甲基丙烯腈对SD妊娠大鼠的毒性

选取体重140～145g成年SD雌雄大鼠,常规饲养1周后使其交配4d,雌鼠阴道涂片发现精子者作为妊娠开始。然后按如下分组并染毒,1个对照组和3个实验组(分别记为Ⅰ、Ⅱ、Ⅲ、组),每组6只妊娠大鼠,将甲基丙烯腈(MeAN,纯度>99%)溶于红花油中灌胃染毒。Ⅰ组于妊娠第1周每天给予MeAN50mg/kg体重(0.25 LD_(50))以观察MeAN对妊娠早期的影响;以上述相同的剂量于妊娠第2周给Ⅱ     

预防型抗氟剂(Ⅰ型-1)遗传毒性的实验研究

为了探讨预防型抗氟剂(Ⅰ型-1)的遗传毒性,选用雄性昆明种小白鼠30只,随机分为阴性对照组、低、中、高剂量组(剂量分别为200,400,800 mg/kg)、阳性对照组(环磷酰胺50 mg/kg)。剂量组灌胃,每天一次,连续5天。断头取血,进行微核试验和单细胞凝胶电泳实验(SCGE)。结果表明,剂量组不但微核率较低,而且也未出现彗星。提示,预防型抗氟剂(Ⅰ型-1)在200～800 mg/kg 剂量范围内对小鼠无遗传毒性。     

终止10～18周妊娠三种用药方案效果比较

日的:探讨米非司酮配伍米索前列醇终止10～18周妊娠较为理想的用药方案。方法:337例受试者随机分为三组:组Ⅰ(101例)米非司酮口服25m/12h共6次,第4天上午口服米索0.6mg;组Ⅱ(95例)米非司酮口服同组Ⅰ,第4大上午阴道给米索0.6mg;组Ⅲ(141例)米非司酮口服早50mg、晚25mg共2天,第3天上午口服米索0.6mg。结果:①完全流产率组Ⅰ、组Ⅱ、组Ⅲ分别为95.05％、95.78％、92.81％。各组间无显著性差异(P>0.05);②米索用量多少与妊娠周数密切相关,随孕周增 加,用量相对增加,娩出时间延长(P<0.05)。结论:米非司酮配伍米索终止lO～18周妊娠安全、有效,有望取代或部分取代钳刮术,米索阴道用药效果好。     

米非司酮与双炔失碳酯合用对人早孕绒毛、蜕膜分泌功能的影响

目的:探讨米非司酮与双炔失碳酯合用抗早孕的机理。方法:组织细胞培养,放射免疫测定等。结果:米非司酮与不同浓度双炔失碳酯(100nM,200nM,400nM,800nM)合用48h,绒毛组织培养液中hCG、P、E_2及6-keto-PGF_(1α)水平与对照组相比显著下降(P<0.05),TXB_2水平显著升高(P<0.01),6-keto-PGF_(1α)/TXB_2比值显著下降(P<0.05);蜕膜组织培养液中E_2水平与对照组相比下降(P<0.05),TXB_2、TNF-α及IL-2水平显著升高(P<0.05);激素及细胞因子水平变化与双炔失碳酯剂量相关。结论:米非司酮与双炔失碳酯合用可显著改变绒毛、蜕膜组织细胞分泌激素的功能,并改变蜕膜组织TNF-α、IL-2水平。这些改变可能与其抗早孕作用有关。     

新方法药物流产的临床研究

目的探索米非司酮配伍米索前列醇(米索)终止早期妊娠的最低有效剂量及最佳给药方案.方法将213例门诊孕36～84 d要求终止妊娠者随机分为两种不同的治疗组.Ⅰ组106例,米非司酮75 mg,1次/d,连服2 d,第3天晨口服米索0.6 mg.Ⅱ组107例,米非司酮50 mg,12 h后服米索0.2 mg,交替连服2 d,如未流产第3天晨服米索0.2 mg,1次/3 h至流产.结果两组完全流产率分别为86.79%、81.31%(P＞0.05),不全流产清宫有绒毛率分别为5.66%、6.54%(P＞0.05),占清宫者的42.86%、35.00%(P＞0.05).用药量Ⅰ组米非司酮150 mg、米索0.6 mg;Ⅱ组米非司酮最低为50 mg、米索0.2 mg,最高分别为150 mg和1.0 mg.用米非司酮至流产时间Ⅰ组平均55 h,中位数54.25 h;Ⅱ组分别为36.95 h和36 h(P＜0.01).结论减量米非司酮与米索交替间隔给药用于终止早孕效果与常规序贯给药无明显差异,流产时间短于常规法.     

米非司酮配伍前列腺素终止孕10～16周妊娠的临床观察

对米非司酮配伍卡前列甲酯栓(PG05)或米索前列醇(米索)用于120例孕10～16周妊娠妇女(随机分为四组)进行了终止妊娠效果的观察。对象一次或分次服米非司酮200mg后48小时,分别使用米索(Ⅰ、Ⅱ组)或PG05(Ⅲ、Ⅳ组),有效率分别为80.0％、80.0％、96.7％、100％。伍用PG05效果明显优于伍用米索。引流产时间分别为5.79、6.54、5.53、6.49小时,四组间无差异。Ⅲ、Ⅳ组副反应高于Ⅰ、Ⅱ组。结论:米非司酮200mg配伍PG05或米索是终止孕10～16周妊娠安全有效的方法。观察中PG05的效果高于米索,考虑可能与米索的剂量偏低有关。由于存在不全流产率较高及潜在的子宫破裂、宫颈裂伤危险,终止妊娠需加强监护。     

米非司酮配伍米索前列醇和卡前列甲酯栓终止早孕与吸宫流产临床对比研究

本研究采集750例妊娠妇女按自愿选择终止早孕的方法,比较药物(组Ⅰ、Ⅱ)与吸宫(组Ⅲ)的安全性、有效性、可接受性。三组治疗方案:①米非司酮首剂50mg,之后25mg/12h×4+PG05 1mg阴道塞药(组Ⅰ);②米非司酮同前+米索600μg(组Ⅱ);③吸宫流产(组Ⅲ)。结果显示:药流组与吸宫组完全流产率分别为94.2％(476/500)、100％(250/250),两组有显著性差异(P<0.001);不全流产率、失败率三个组分别为:2.4％和0、3.4％和0,组间有明显差异(P<0.01);出血量比月经量增多的对象占19.2％和10％,明显增多的占1.4％和0,组间有显著差异(P<0.05);出血持续时间为11.0±7.1和4.8±3.1,组间有显著差异(P<0.01);转经时间两种流产无统计学意义;两种流产的副反应,药流组的眩晕、下腹痛发生率高于手术组,而恶心、呕吐发生率低于手术组,两组间有显著性差异(P<0.01);对此次流产表示满意的药流组和吸宫组为:79.6％和84.4％,两组中分别有86.4％以及64.0％的对象在下一次发生意外妊娠时,仍然愿意采用本次选择的方法终止早孕。结果提示两种流产仍是目前终止早孕的最佳方法,药物流产作为终止早孕方法的补充是安全,有效、可接受的。     

焦性没食子酸对雌性小鼠抗生育作用的研究

目的:探讨焦性没食子酸对雌性小鼠生育的影响。方法:实验分组为空白凝胶(基质)对照组、阴道给药3个剂量组、腹腔注射组及阳性药物组,分别阴道给予空白凝胶、焦性没食子酸10 mg/kg、30 mg/kg和100 mg/kg、腹腔注射给予焦性没食子酸100 mg/kg及阳性药物组给予米非司酮。实验时将性成熟ICR雌性小鼠与雄性小鼠按3∶1合笼12 h,次日清晨检查雌鼠的阴栓,见阴栓者定为受孕第1天(D1)。分别按照实验分组给药,统计各组孕鼠数、胎鼠数和受孕率,观察焦性没食子酸对雌性小鼠生育力、抗着床作用及抗早孕作用的影响;同时留取各组小鼠子宫标本,采用HE染色子宫组织切片观察焦性没食子酸对雌性小鼠子宫内膜组织结构的影响。结果:焦性没食子酸具有降低雌性小鼠生育力、抗着床、抗早孕的作用,其抗着床作用最为显著;焦性没食子酸能降低雌鼠子宫内膜的增生与水肿表现。结论:焦性没食子酸具有对雌性小鼠的抗生育作用。     

不同剂量丙球联合地塞米松治疗小儿急性ITP的疗效观察

目的:探讨不同剂量丙种球蛋白(IVIG)联合地基米松治疗小儿急性特发性血小板减少性紫癜(ITP)的临床疗效.方法:将43例急性ITP住院患儿分为3组,给予IVIGⅠ组0.4～0.5/kg·d×3天、Ⅱ组0.4/kg·d×5天、Ⅲ组1.0/kg·d×2天.联合使用地塞米松1mg/kg·d静滴,5天后减量或改为口服强的松逐渐减量,总疗程3～4周.结果:三组治疗后的显效率和有效率分别为:Ⅰ组86.67%、93.33%,Ⅱ组83.33%、94.44%,Ⅲ组90%、90%.三组治疗后的血小板达正常值时间分别为:Ⅰ组3.62±1.66天,Ⅱ组4.27±1.11天,Ⅲ组3.89±2.09天.结论:三种剂量IVIG联合地塞米松治疗小儿急性ITP的临床疗效无显著性差异.     

双炔失碳酯用于性交后紧急补救措施的研究

对未采取有效避孕措施性交后要求避孕的妇女,在性交后48h内,给予口服双炔失碳酯(53号抗孕片),首次7.5mg,12h后重复。与正常妇女未避孕时性交后受孕的可能性进行比较。结果:服药后受孕率明显降低,恶心、呕吐等副反应小,对月经周期及月经量影响小。提示:双炔失碳酯做为一种紧急补救措施,其有效性和可接受性令人满意。     

白藜芦醇的雌激素样作用研究

为研究白藜芦醇在体内的雌激素样作用 ,给刚断乳小鼠分别皮下注射和灌胃不同剂量的白藜芦醇 ,观察该物质对子宫和阴道的影响。结果显示 ,2 0mg kg .BW的白藜芦醇可明显促进未成熟小鼠阴道开口 (P <0 0 5 )和阴道上皮角化 ,显著增加子宫重量及其系数 (P <0 0 5 ,P <0 0 1) ,并可使子宫内膜柱状上皮增厚或腺体增生。结果表明白藜芦醇在体内具有雌激素样作用。而口服白藜芦醇的雌激素活性明显弱于皮下注射     

Anordiol is more potent than anordrin for terminating pregnancy when administered with RU 486

In view of the unexpected ability of anordrin to synergize with RU 486 in terminating pregnancy, it was pertinent to examine the actions of the dihydroxylated metabolite of anordrin, anordiol, alone and in combination with RU 486. Doses of RU 486 (1 mg/kg/day) and anordiol (0.6 mg/kg/day) that were ineffective when given alone terminated pregnancy with complete resorption of embryos when administered together. A smaller dose of anordiol than anordrin is required to achieve this synergistic effect with RU 486. This anordrin metabolite increased uterine weight in the ovariectomized rat similar to estradiol. The estrogenicity of anordiol in the uterine weight assay was about 1/120 of that of estradiol. Anordiol does not exert antiestrogenic activity in the uterine weight assay when administered at doses that terminate pregnancy. Administration of anordiol at doses that do not terminate pregnancy resulted in a significant suppression of serum progesterone concentrations during the period of medication; these observations suggest that anordiol has an inhibitory effect on progesterone biosynthesis. When the same dose of anordiol was given concomitantly with sufficient RU 486 (e.g., 1 mg/kg/day) to terminate pregnancy, the progesterone levels were reduced to low levels throughout the experiment. These observations support the postulate that the actions of anordrin are mediated by its metabolite, anordiol. The administration of anordiol plus RU 486 results in a more dramatic change in the functional progesterone:estradiol ratio than when either agent is administered alone.     

Effect of Anordrin on serum levels of sex hormone binding globulin, caeruloplasmin and ovarian function

Ten doses of 7.5 mg Anordrin were administered on alternate days from day 5 of the menstrual cycle to 20 women. Serum concentrations of both SHBG and CP were significantly increased after the fourth dose but the increases were minor compared to those produced by ethynyloestradiol. Two weeks after stopping Anordrin, serum concentrations of the proteins were still elevated in most women. Ovarian activity was studied in 8 women; serum oestradiol and progesterone concentrations indicated that ovulation occurred at the normal time in three women but was delayed for two weeks or more in the remaining five. The findings suggest that in humans, Anordrin acts as a weak oestrogen and may also have antioestrogenic activity.     

Synergistic effects of DL111-IT combined with mifepristone on termination of early pregnancy in rhesus monkeys

The objectives of this study were to determine the synergistic effects of DL111-IT in combination with mifepristone (RU486) on termination of early pregnancy in rhesus monkeys. Pregnancy was confirmed by tactile sensation of pregnant uterus via anus with finger and ultrasound examination. Pregnancy termination was obtained with vaginal bleeding and abortion materials including fetuses and placentae after treatment. With multiple doses of DL111-IT or RU486 given alone between d24 and d50 of gestation, pregnancy arrests were obtained in 40% (2/5) of monkeys treated with DL111-IT intramuscularly (im) (25 mg x kg(-1) x d(-1) x 3 days), in 20% (1/5) of monkeys treated with 9 mg x kg(-1) x d(-1) x 2 days, and 4.5 mg x kg(-1) on day 3 with RU486 intragastrically (ig). DL111-IT (25 mg x kg(-1) on day 1, im) in combination with RU486 (the same treatment as above) resulted in 100% (10/10) termination of pregnancy and uterine bleeding lasted 6.6 +/- 1.3 days. RU486 (as above treatment) in combination with misoprostal (Miso, 109 microg x kg(-1) on day 3, ig) showed 71.4% (5/7) termination of pregnancy, and uterine bleeding lasted 12.9 +/- 9.6 days. The synergistic effect of DL111-IT plus RU486 enhances termination of early pregnancy and significantly shortens the bleeding time than RU486 plus Miso does in rhesus monkeys.     

吡哆素L-2-吡咯烷酮-5-羧酸酯对雄性生殖毒性的作用机制

目的　研究吡哆素L 2 吡咯烷酮 5 羧酸酯 (MTDX)对雄性大鼠生殖毒性作用的机制。方法　分别用小鼠多终点体内实验和Hershberger实验观察MTDX的雌激素样作用和抗雄激素作用。在小鼠多终点体内实验中 ,摘除卵巢的NIH雌性小鼠分别每天给予MTDX 0、6 4 0、15 0 0和 4 0 0 0mg/kg,连续 5d ,观察子宫 /体重比、子宫积液、动情周期转换、子宫上皮高度及子宫基质细胞层厚度 5项指标。在Hershberger实验中 ,去势SD雄性大鼠分别每天给予MTDX 0、6 0 0和 15 0 0mg/kg ,同时给丙酸睾丸酮 12 5mg/kg,连续 10d ,测量大鼠雄激素依赖组织重量。结果　小鼠多终点体内实验中 ,MTDX6 4 0、15 0 0和 4 0 0 0mg/kg组切除卵巢小鼠的子宫 /体重比值分别为 (1 33、1 38、1 31)× 10 -4,与对照组的 1 2 2× 10 -4比较 ,差异无显著性 ;MTDX 15 0 0和 4 0 0 0mg/kg组小鼠子宫上皮细胞高度 (0 90和 1 0 3μm)和基质细胞层厚度 (3 38和 3 2 5 μm)与对照组 (0 85和 2 77μm)比较 ,均差异无显著性。在Hershberger实验中 ,MTDX 15 0 0mg/kg组大鼠的精液囊和前列腺、提肛肌、球海绵体肌的脏器系数值分别为 1 13、0 17、0 4 2 ,均显著低于对照组的 1 4 6、0 2 4、0 70 ;MTDX 6 0 0mg/kg组大鼠的精液囊和前列腺的脏器系数值为 1     

A relationship between estrogenicity and antifertility activity of 1-diphenylmethylenyl-2-methyl-3-ethyl-4-acetoxycyclohexane (ORF 8511) and similar nonsteroidal anti-implantive agents

Several nonsteroidal estrogens, such as ORF 3858 and F6103, which inhibit pregnancy in experimental animals when given postcoitally, have been previously described. ORF 8511 (1-diphenylmethylenyl-2-methyl-3-ethyl-4-acetoxycyclohexane) which is structurally similar to these compounds was studied for its postcoital antifertility activity and estrogenicity in rats, hamsters, mice and rabbits. Results of these studies suggest a relationship between these two biological endpoints. ORF 8511 produced uterotropic stimulation in the rat at microgram doses and totally inhibited implantation at 250 μg/kg/day administered on days 1–6 of pregnancy. However, the other species were considerably less sensitive to the compound with respect to both parameters. The compound stimulated tubal transport in rats at its minimum effective dose for antifertility activity as did diethylstilbestrol, a known estrogen. In the hamster, a species relatively insensitive to the antifertility effect of ORF 8511, endogenous estrogen titres during early pregnancy were higher than those in the rat. These data suggest that ORF 8511 and similar nonsteroidal compounds may owe their postcoital antifertility activity to their estrogenicity and that estrogens may act as pharmacological agents only in species with low normal endogenous estrogen titres.     

Effects of DL111-IT or combined with RU486 on uterine polyamines biosynthesis in rats during early gestation.

DL111-IT, a non-hormonal contragestional agent, revealed synergistic effects in combination with mifepristone (RU486) in some species. The present study was undertaken to clarify the role of DL111-IT when used alone or plus RU486 on uterine polyamines biosynthesis, histologic alteration of decidual cells, and antifertility activity in rats. The levels of polyamines in pregnant rat uterus were determined by formed benzoyl chloride derivatives of polyamines for RP-HPLC. The results showed that all the treated groups including DL111-IT 2.8 mg. kg(-1). d(-1), RU486 3.0 mg. kg(-1). d(-1), and DL111-IT 0.56 mg. kg(-1). d(-1) plus RU486 0.6 mg. kg(-1). d(-1) caused 100% early pregnancy arrest. Uterine putrescine, spermidine, and spermine levels in comparison with vehicle control were declined significantly from d7 of gestation (1 day after treatment) to d9 or d14 (3 days or 8 days after treatment) by Duncan's multiple range test, and accompanied by histologic alterations, edema, degeneration and dissolution of decidual cells with nuclei indefinite in appearance on d8 of gestation (2 days after treatment). The combined administration at lower doses caused the most injury. The data verified that the decrease in uterine polyamine levels and subsequent decidual cells injuries were the critical role of early pregnancy arrest induced by DL111-IT or RU486. The two compounds used in combination with lower dosages revealed greatly synergistic effects.     

终止妊娠新药抗孕唑啉的一般药理作用研究

目的:研究抗孕唑啉(L14105)对呼吸、心血管、中枢神经系统及子宫肌的作用。方法:用麻醉猫观察该药对血压、呼吸、心电图的影响;描记家兔大脑皮层电图的变化;L14105与戊巴比妥钠合用对小鼠睡眠时间的影响;观察对子宫肌收缩的影响。结果:静脉注入60mg/kg体重使猫心率减慢,120mg/kg体重对血压和呼吸均无影响;50mg/kg体重对家兔皮层电图无明显影响;肌肉注射50mg/kg体重与戊巴比妥钠合用使小鼠睡眠时间延长;对离体或在位子宫肌均可增强收缩力。结论:L14105可增强子宫肌节律性收缩;与戊巴比妥钠合用具中枢抑制协同作用;大剂量可减慢心率。