黄体中期给予米非司酮对生殖激素和子宫内膜的影响

研究黄体中期单次应用小剂量米非司酮对子宫内膜发育、雌孕激素受体及生殖激素水平的影响。对正常生育妇女进行前瞻性、自身对照研究,在2个连续的月经周期中进行研究,包括一个对照周期和一个用药周期。在对照及服药周期于LH＋6－8d取子宫内膜,同时抽取肘静脉血;在用药周期于取材前一天口服米非司酮50mg。结果显示黄体中期一次性服用米非司酮50mg不影响LH、E2和P的分泌,但显著降低FSH的分泌,并明显延迟子宫内膜的成熟,降低ER和PR在子宫内膜腺体的表达。提示黄体期应用较小剂量米非司酮对子宫内膜产生的影响可能足以阻止着床,这可能是米非司酮用于紧急避孕的机制之一。     

米非司酮和孕三烯酮对子宫内膜异位患者激素和妊娠情况的影响

目的观察并比较米非司酮和孕三烯酮对子宫内膜异位(EMs)患者激素水平和妊娠情况的影响。方法 80例EMs患者随机分为两组,分别在腹腔镜术后接受米非司酮或孕三烯酮治疗,疗程6个月。观察激素水平和妊娠情况。结果米非司酮组和孕三烯酮组的总缓解率分别为97.5%和95.0%,差异无统计学意义(P>0.05)。治疗后两组的雌二醇(E2)、孕酮(P)、促黄体生成素(LH)和促卵泡成熟素(FSH)均明显下降,与治疗前比较差异具有统计学意义(P<0.05),但治疗后两组比较差异无统计学意义(P>0.05)。两组1年妊娠率分别为30.0%和32.5%,差异无统计学意义(P>0.05)。结论子宫内膜异位患者腹腔镜术后采用米非司酮或孕三烯酮治疗,对患者激素水平和受孕情况的影响相当,临床疗效相似。     

米非司酮治疗子宫肌瘤的疗效观察及对血清生殖激素的影响

对40例子宫肌瘤行米非司酮治疗的临床疗效观察，治疗前后血清生殖激素的变化，部分病例随访，初步探讨子宫肌瘤药物治疗的方法、适应证和副作用。认为小剂量米非司酮治疗子宫肌瘤安全有效，副作用轻微。但部分随访病例在治疗后出现复发情况，因此米非司酮不能完全取代手术。     

小剂量米非司酮对生殖内分泌的影响

目的探讨小剂量米非司酮对生殖内分泌的影响。方法随机抽取门诊就诊的子宫肌瘤或子宫腺肌病患者40例。均于月经的第5天开始服用米非司酮6.25mg/d,连续服用4个月,于用药前及停药1周内测量卵巢的面积以估计卵巢的大小,空腹测量血清雌二醇、FSH(卵泡刺激素)的水平,应用SPSS11.5统计软件进行数据处理。结果米非司酮治疗后,右卵巢面积小于治疗前,两者比较,差异有显著性(P<0.01)。米非司酮治疗前血雌二醇为卵泡期水平,治疗后为绝经期水平,两者比较,差异有显著性(P<0.01)。米非司酮治疗前后FSH差异无显著性(P>0.05)。结论小剂量米非司酮对垂体没有明显抑制作用,但具有雌激素样的负反馈作用;小剂量米非司酮通过抗雌激素样作用直接作用于卵巢,导致卵泡发育停止,从而使卵巢激素缺乏周期性变化而出现闭经,并伴随出现卵巢缩小及更年期症状。     

绝经前子宫切除对女性体内生殖激素的影响分析

目的探讨绝经前子宫切除后体内生殖激素的变化.方法对47例对照组和70例子宫良性病变行子宫及卵巢(双侧或单侧)切除后体内6种生殖激素进行测定.结果六种激素变化为卵泡刺激素(FSH)、黄体生成激素(LH)显著升高,孕酮(P)、雌二醇(E2)及催乳激素(PRL)、睾酮(T)显著降低.结论子宫切除后体内生殖激素改变影响妇女的健康及生活质量,导致疾病的发生.故提示对患者治疗方式不主张擅自切除子宫和卵巢,尽量做到去除病变,保留器官功能.     

米非司酮对女性生殖内分泌系统的影响

米非司酮是一种抗孕激素类药物,最初用于抗早孕、药物流产、紧急避孕等,后来随着对其作用机理的进一步探讨,发现米非司酮具有抗雌激素样作用,被用来治疗雌激素依赖性疾病和肿瘤,如子宫肌瘤、子宫内膜异位症、乳腺癌、子宫内膜癌等。在治疗过程中发现连续应用米非司酮可引起闭经,故认为米非司酮对生殖内分泌轴有一定影响。本文就米非司酮对生殖内分泌系统的影响作一综述。     

黄体生成激素治疗子宫肌瘤和子宫内膜异位症20例

黄体生成激素（ＧｎＲＨ＿Ａ）是一种下丘脑分泌的九肽,按给药方法不同，对下丘脑-垂体-性激素轴可有兴奋或抑制作用。其抑制作用为治疗性激素依赖性疾病开辟了一条新的治疗途径。我院在１９９５～１９９６年期间应用国产的ＧｎＲＨ＿Ａ治疗围绝经期子宫肌瘤,子宫内膜异位症及功血。现将疗效报道如下。１资料和方法１１临床资料１９９５年３月～１９９６年４月我院门诊诊断为子宫肌瘤、子宫内膜异位症及功血病例共２０例,其中子宫肌瘤６例,内异症１０例,功血４例。年龄为２９～５５岁,平均４２岁,其中１６例年龄大于４５岁。６例子宫如孕２…     

小剂量米非司酮对子宫内膜的影响

目的通过研究小剂量米非司酮对子宫内膜的影响,探讨长期应用小剂量米非司酮的安全性。方法随机抽取门诊就诊的子宫肌瘤或子宫腺肌病患者40例,年龄为(39.11±7.98)岁。均于月经的第5天开始服用米非司酮12.5mg/d,连续服用1个月,自第2个月开始,每天服用6.25mg/d,连续服用3个月,共计4个月经周期(120d)。分别于服药前月经周期的卵泡期(月经的第1～9天)及服药第120天至停药一周内进行随访。每次随访均做阴道超声测量子宫内膜厚度,取子宫内膜行HE染色、免疫组化二步法测PCNA指数,测量血E2、FSH、谷丙转氨酶(GPT)、肌酐(Cr),记录阴道流血情况及不适症状等。应用SPSS11.5统计软件进行数据处理。结果①米非司酮治疗前血雌二醇为(69.73±41.58)pg/mL,为卵泡期水平,治疗后为(35.88±10.98)pg/mL,为绝经期水平,两者比较,差异有显著性(P<0.01)。②米非司酮治疗前后FSH分别为(5.02±2.91)IU/L及(5.88±1.73)IU/L,两者比较,差异无显著性(P>0.05)。③病理报告示治疗后内膜转化率为33.3%,部分内膜发生增生过长,未发现不典型增生;米非司酮治疗前后子宫内膜的PCNA指数分别为(795.80±59.70)及(820.60±48.05),两者比较,差异无显著性(P>0.05)。④米非司酮治疗后谷丙转氨酶为(19.50±7.91)U/L,肌酐为(68.61±25.56)μmol/L,与治疗前比较,差异无显著性(P>0.05)。结论小剂量米非司酮具有微弱的雌激素样作用,对子宫内膜无抑制,服用小剂量米非司酮4个月,可导致内膜出现增生过长,但未发现不典型增生情况,说明此种用药方法是相对安全的,但其长期应用的安全性有待进一步探讨。     

米非司酮对子宫肌瘤和子宫腺肌病的影响

目的　探讨米非司酮对子宫肌瘤与子宫腺肌病的作用机制及临床治疗效果。方法　选择门诊病人 ,子宫肌瘤病人 5 0例 ,全部为壁间肌瘤 ,其直径为 3～ 7cm ,子宫腺肌病 10例。按年龄段分成四组 ,月经干净后第 3天开始口服米非司酮 2 5mg ,日服 1次 ,连续服用 3个月 ,观察肌瘤大小的变化。此外 ,采用多点法测定子宫肌瘤、子宫腺肌病及正常子宫肌层组织中孕激素受体含量。结果　子宫肌瘤体积于用药第 4周开始下降 ,平均下降了 19% (19%± 3 6 % ) ,第 8周平均下降了 39 3% (39 3 %± 5 4% ) ,至 12周明显下降 ,平均下降了 48 6 % (48 6 %± 8 7% ) ,统计学处理 ,差异有显著意义 (P <0 0 0 1)。从个别病例上观察仅有 3例无变化 ,而 4例体积下降 72 %。各组间差异无显著意义。子宫腺肌病病人子宫体积平均减少了 17 6 % ,统计学处理差异有显著意义 (P <0 0 5 ) ,临床症状减轻或消失。服药 3个月后追踪 2 0例病人 (18例子宫肌瘤 ,2例子宫腺肌病 ) ,子宫彩超检查显示 ,子宫与子宫肌瘤体积无增大趋势。子宫肌瘤与子宫腺肌病病人子宫肌层组织内的孕激素受体含量高于正常的子宫肌层组织。结论　子宫肌瘤组织与子宫腺肌病病人子宫肌层组织孕激素受体表达高于正常子宫肌层组织 ,米非司酮阻断孕激素作用 ,使子宫肌瘤体     

米非司酮腹腔内给药对子宫肌瘤模型大鼠的干预作用

［摘要］目的观察米非司酮腹腔内给药对实验性大鼠子宫肌瘤的治疗作用，并探讨其可能的作用机制。方法将SD雌性大鼠75只随机分为5组。正常组15只，其余大鼠以苯甲酸雌二醇和黄体酮诱发子宫肌瘤模型。分为模型组及米非司酮腹腔内给药低、中、高剂量（0.56 ，1.12 ，2.24 mg·kg-1·d-1，腹腔内注射）组各15只。正常组、模型组每只每天腹腔内注射等量0.9%氯化钠溶液，共12周。末次用药后24 h将所有大鼠称重，酶标记单克隆抗体法测定血清雌二醇（E2 ）和孕激素（P）水平，放射免疫法测定血清表皮生长因子（EGF）水平；随后处死大鼠，剖腹先观察子宫大体形状，剪取子宫称重，以子宫重量/ 体重(mg·g-1) 计算子宫系数；免疫组化染色观察子宫平滑肌细胞雌、孕激素受体的表达。结果模型组大鼠血清 E2 、P和 血清EGF 水平均明显高于正常组，子宫重量明显增加，子宫系数变大，子宫平滑肌细胞雌、孕激素受体的表达明显升高。米非司酮腹腔内给药可明显降低大鼠血清 E2 、P及EGF 水平，抑制子宫平滑肌细胞雌、孕激素受体的表达，以2.24 mg·kg-1·d-1剂量组的作用最明显。结论米非司酮腹腔内给药对实验性大鼠子宫肌瘤有明显的治疗作用。其抗瘤机制可能为：①降低体内雌、孕激素及其受体水平，直接对抗孕酮活性并产生抗E2作用，从而使雌、孕激素效应显著降低，导致肌瘤体积缩小，子宫重量减轻，子宫系数变小；②降低血清EGF水平，抑制 EGF EGF R对肿瘤细胞的增殖刺激作用，从而使肌瘤体积缩小。     

米非司酮配伍卡孕栓和米索前列醇片阴道给药应用于大月份钳刮术前准备的效果比较

目的探讨米非司酮分别配伍卡孕栓阴道给药和米索前列醇片阴道水化给药应用于大月份钳刮术前准备的效果比较。方法对1000例妊娠10~12周早孕妇女要求终止妊娠实施钳刮术,将病例随机分成两组,卡孕栓组和米索前列醇组,每组500例,术前均同样方法口服米非司酮六片,即空腹早两片晚一片的服用方法,第3天来院行阴道上药。上药后记录患者的阴道流血,宫颈软化程度,时间,腹痛程度,上药次数及患者的腹泻过敏等副反应情况。结果卡孕栓组和米索前列醇组阴道流血量,宫颈软化程度时间,腹痛情况经统计学比较差异无显著性意义,米索前列醇组具有卡孕栓组同样的效果但其具有只需一次上药,无腹泻副作用,安全价廉等优势。结论米非司酮配伍米索前列醇片阴道水化给药可以替代米非司酮配伍卡孕栓阴道上药应用于大月份钳刮术前准备,其安全,价廉,宫颈软化效果好,副作用小等优点,是值得推广使用的。     

The Bioavailability of Dermatological and Other Topically Administered Drugs

The literature addressing determination of the bioavailability of dermatological and other topically administered drugs has been reviewed. The various methods employed, their advantages and drawbacks, have been identified and evaluated. The state of the art and the success of topical bioavailability assessment are discussed in the light of the information presented. It is concluded that, although current methodology ensures the responsible use of topical medicaments, the techniques are, on the whole, quantitatively inadequate. A number of recommendations are proposed as possible improvements to the approaches now undertaken, and specific measurements for drugs in different therapeutic categories are suggested. The ultimate objective of this survey is to catalyze the establishment of straightforward, objective, quantitative, and reproducible methods to evaluate topical bioavailability and to reduce significantly, thereby, the incidence of bioinequivalence and pharmacological inactivity observed following drug dosing to the skin.     

中心静脉压监测和血气分析在宫-腹联合子宫肌瘤切除术患者前列腺电切综合征的预防作用

目的 评价中心静脉压(CVP)和血气分析腔测在宫-腹联合子宫肌瘤切除术患者水中毒的预防作用.方法 将24例患者分为两组,每组12例,两组患者均在气管内插管静吸复合全麻下行手术,CVP组术中连续测定CVP及袖套血压、心率、血氧饱和度、气道阻力.当CVP＞12 cmH2O时,行血气分析,并行利尿等对症处理.对照组监测指标除...     

Hormones and antihormones. The steroidal model

Antiglucocorticoids despite very limited clinical application (in contrast with other antisteroids) are extensively studied, since the glucocorticoid receptor, present in numerous target cells, constitute a very convenient experimental model. Structure activity relationships of a series of 17 beta-carboxamide derivatives of dexamethasone are described. The affinity of these compounds for the glucocorticoid receptor depends on the nature of the 17 beta-side chain substituent. An effect is observed at a rather large distance from the steroid nucleus. Maximal affinity is obtained with aromatic substituents. Antiglucocorticoid activity seems to be correlated with a high dissociation rate constant of the steroid receptor complexes and probably exclude the existence of a very active antiglucocorticoid in these series. Dexamethasone 17 beta-carboxamide derivates share with all other antiglucocorticoids tested the same ability to stabilize a high molecular form of the receptor associated to HSP90, a heat shock protein, in intact cells.     

米非司酮配伍米索前列醇在稽留流产中的临床应用

目的：探讨米非司酮配伍米索前列醇片在稽留流产中的应用效果。方法：对2008年1月-2010年2月对妊娠12～18周稽留流产孕妇102例,按入院时间顺序单数选为实验组（A组）,双数选为对照组（B组）,各51例,实验组服用米非司酮配伍米索前列醇片,与对照组苯甲酸雌二醇肌注后再行清宫术比较。结果：实验组完全流产43例,占84．3％：不全流产7例,占13．7％;流产失败1例,占2．0％。阴道流血量〈60ml 45例,占88％;阴道出血量〉60ml 6例,占12％;清宫人数8例,清宫时间〈5min 8例,占100％,〉5main 0例。对照组完全流产3例,占5．8％;不全流产4例,占7．8％;流产失败44例,占86．4％。阴道流血量〈60ml 31例,占56％;阴道出血量〉60ml 20例,占44％。清宫人数48例。清宫时间〈5min 42例,占87．5％;〉5min 6例,占12．5％。结论：米非司酮配伍米索前列醇在稽留流产中应用效果显著。值得临床推广应用。     

The Redistribution of Bulk Aqueous Phase Phospholipids During Thermal Stressing of Phospholipid-stabilized Emulsions

Abstract— The mechanism of the stabilization of triglyceride emulsions by phospholipids has been studied using an HPLC-FID method to determine phosphatidylcholine, lyso-phosphatidylcholine and phosphatidylethanolamine in the oil and aqueous phases of a model emulsion consisting of soybean oil 20 g, egg phospholipid 1·2 g, glycerol 2·25 g and water to 100 mL. It was shown that, on heat sterilization of the emulsions, the phospholipids rapidly relocate from the aqueous phase to the oil phase. It is suggested that the phospholipids concentrate in the oil/water meso phase, forming a cubic liquid crystalline phase, the bulk of which is converted to a lamellar phase on cooling, and that this organization of interfacial material accounts for the enhanced stability of phospholipid emulsions after heat sterilization.     

The Developmental Toxicity of Orally Administered Oxytetracycline in Rats and Mice

The Developmental Toxicity of Orally Administered Oxytetracyclinein Rats and Mice. MORRISSEY, R.E., TYL, R.W., PRICE, C.J., LEDOUX,T.A., REEL, J.R., PASCHKE, L.L., MARR, M.C, AND KJMMEL, C.A.(1986). Fundam. Appl. Toxicol. 7, 434-443. Timed-pregnant CDrats and CD-1 mice were dosed by gavage with oxytetracyclinehydrochloride (OXT) in corn oil on gestational days (gd) 6-15(0, 1200, 1350, or 1500 mg/kg/day for rats; 0, 1325, 1670, or2100 mg/kg/day for mice). Deaths among treated females occurredin a dose-related manner in all OXT dose groups (2-7%, mice;5-24%, rats), but no maternal deaths occurred in the vehiclecontrol groups. Significant dose-related decreases in maternalweight gain during treatment, as well as for corrected gestationalweight gain (i.e., maternal gestational weight gain minus graviduterine weight), were observed at all doses in rats but notin mice. Gravid uterine weight was reduced in a dose-relatedmanner only in mice, with the high-dose group significantlyreduced compared to the control group. At termination (gd 20,rats; gd 17, mice), the status of uterine implantation siteswas recorded and live fetuses were weighed. Fetuses were examinedfor external, visceral, and skeletal abnormalities. There wereno significant effects of OXT in either species on the incidenceof postimplantation loss (resorptions plus dead fetuses) ormalformations. In both species, there was a significant trendtoward reduced fetal body weight, and each group of rats receivingOXT was significantly reduced compared to the control group.Administration of OXT during organogenesis at doses exceedingthe therapeutic range for humans produced maternal and fetaltoxicity, but did not produce any treatment-related increasein malformations.     

The Developmental Toxicity of Orally Administered Theophylline in Rats and Mice

The Developmental Toxicity of Orally Administered Theophyllinein Rats and Mice. LIND-STRÖM, P., MORRISSEY, R. E., GEORGE,J. D., PRICE, C. J., MARR, M. C, KJMMEL, C. A., AND SCHWETZ,B. A. (1990). Fundam. Appl. Toxicol. 14, 167–178. Theophylline(THEO), a widely prescribed anti-asthmatic, was evaluated fordevelopmental toxicity. It was administered continuously onGestational Days 6 through 15 to pregnant Sprague-Dawley (CD)rats in the feed (0,0.15,0.30, or 0.40%) and to pregnant Swiss(CD-1) mice in the drinking water (0,0.075, 0.15, or 0.20%).Estimated intake of THEO for rats was 0, 124, 218, or 259 mg/kg/day,while for mice it was 0, 282, 372, or 396 mg/kg/day. In rats,maternal weight gain parameters (weight gain during gestationand treatment, as well as corrected weight gain) decreased at0.40%. While food consumption was lower only in the 0.40% treatmentgroup, water consumption was higher in all treated groups. Therewas a dose-related decreasing trend in gravid uterine weight.The number of live fetuses per litter decreased at 0.40% andthe average male and female fetal weight per litter decreasedat 0.30 and 0.40%. There was no increase in malformations. Inmice, maternal corrected body weight and weight gain duringgestation decreased at 0.15 and 0.20%, and weight gain duringtreatment and gravid uterine weight decreased at 0.20%. Waterconsumption was reduced by as much as 30-45% of controls at0.15 and 0.20%, respectively, while food consumption did notchange with THEO treatment There was an increase in percentageresorp-tions per litter and a decrease in the average male andfemale fetal weight per litter at 0.15 and 0.20%. An increasingtrend was noted for percentage malformed fetuses per litter,and percentage litters with externally malformed fetuses wereslightly increased in the mid- and high-dose groups. However,these increases were not statistically significant. In summary,there were developmental effects seen in rats at a dose (0.30%)that did not produce overt maternal toxicity, but the adversedevelopmental effects in mice were observed at doses that causedreduced maternal water consumption and body weight gain. Itis possible that water deprivation contributed to the effectsseen in mice after THEO treatment. For maternal toxicity, noobservable adverse effect levels (NOAELs) were 218 mg/kg forrats and 282 mg/kg for mice. NOAELs for developmental toxicitywere 124 mg/kg for rats and 282 mg/kg for mice. These NOAELsare approximately 10-to 30-fold greater than doses requiredto maintain humans on serum THEO concentrations that are clinicallyuseful.