Protective effects of progesterone on implantation failure induced by dibutyltin dichloride in rats

We previously showed that dibutyltin dichloride (DBTCl) at 7.6 mg/kg and higher on days 0-3 of pregnancy caused implantation failure and a decline in serum progesterone levels in rats and hypothesized that the decline is responsible for the implantation failure. This study was conducted to determine the protective effects of progesterone on the DBTCl-induced implantation failure in rats. Rats were given oral DBTCl at 0, 7.6, or 15.2 mg/kg on days 0-3 of pregnancy and/or subcutaneous progesterone at 2 mg/rat on days 0-8 of pregnancy. The reproductive outcome was determined on day 9 of pregnancy. No effects of administration of progesterone alone on the pregnancy rate and number of implantations were found. The pregnancy rate and number of implantations were significantly decreased after administration of DBTCl alone. The pregnancy rate and number of implantations were higher in the groups given DBTCl and progesterone than the groups given DBTCl alone. The present data indicate that progesterone protects, at least in part, against the DBTCl-induced implantation failure and support our hypothesis that the decline in progesterone levels is a primary mechanism for the implantation failure due to DBTCl.     

Developmental toxicity of dibutyltin dichloride given on three consecutive days during organogenesis in cynomolgus monkeys

We previously reported that the administration of dibutyltin dichloride (DBTCl) by nasogastric intubation during the entire period of organogenesis, days 20–50 of pregnancy, was embryolethal, but not teratogenic, in cynomolgus monkeys. The present study was conducted to further evaluate the developmental toxicity of DBTCl given to pregnant monkeys on 3 consecutive days during organogenesis. Cynomolgus monkeys were given DBTCl at 7.5?mg/kg body weight/day by nasogastric intubation on days 19–21, 21–23, 24–26, 26–28, 29–31, 31–33, or 34–36 of pregnancy, and the pregnancy outcome was determined on day 100 of pregnancy. Embryonic/fetal loss was observed in 1 female given DBTCl on days 19–21, 2 females given DBTCl on days 24–26, and 1 female given DBTCl on days 34–36. There were no effects of DBTCl on developmental parameters in surviving fetuses, including fetal body weight, crown-rump length, tail length, or placental weight. No external, internal, or skeletal malformations were detected in fetuses in any group. DBTCl did not affect the incidence of fetuses with skeletal variation or skeletal ossification of fetuses. These data confirm our previous findings that DBTCl was embryolethal, but not teratogenic, in cynomolgus monkeys.     

Teratogenicity and embryotoxicity of titanocene dichloride in mice

The teratogenic and embryotoxic effects of the antitumor agent titanocene dichloride (TDC) were investigated after application of single doses of TDC (30 or 60 mg/kg) to pregnant mice on days 8, 10, 12, 14 or 16 of gestation. The fetuses were removed on day 18 by caesarian section and examined for external, internal and skeletal malformations as well as for toxic phenomena. The most striking result was the occurrence of cleft palate in numerous fetuses (10% of the fetuses, 30 mg/kg; 40-50%, 60 mg/kg) after TDC application on days 10 and 12. Besides the additional appearance of costal malformations in some fetuses, no other malformations were recognizable. On the other hand, the embryotoxic influence of TDC was significant and caused diminution of the number of live fetuses per litter, marked and dose-dependent reduction of mean fetal body weight after TDC application on day 8 through day 16 and distinct retardation of skeletal ossification.     

动态监测血清 CA125 及孕酮在预测早期异位妊娠结局的意义

目的动态监测早孕期血清CA125及孕酮水平,探讨其在预测早期异位妊娠结局的价值。方法选取2011年3月至2013年2月于该院门诊正常妊娠及疑为异位妊娠或先兆流产而入院的80例患者作为研究对象,按妊娠结局分为正常妊娠分娩组20例,先兆流产保胎成功分娩组20例,先兆流产发展为稽留流产组20例,异位妊娠组20例,对所有病例进行血清CA125及孕酮动态监测,并进行统计学分析与处理。结果先兆流产保胎成功分娩组孕酮水平高于稽留流产组,明显高于异位妊娠组,均有明显统计学意义（P〈0．05）。早期妊娠阶段,正常妊娠分娩组、先兆流产保胎成功分娩组、先兆流产保胎失败组,孕酮水平差异无统计学意义（P〉0．05）。早期妊娠阶段,4组血清CA125平均水平均高于正常值且呈缓慢上升趋势,正常妊娠分娩组、先兆流产保胎成功分娩组呈缓慢上升趋势,两者无明显统计学意义（P〉0．05）,而先兆流产发展为稽留流产组及异位妊娠组的CA125水平高于前2组（P〈0．05）,但2组无明显统计学意义（P〉0．05）,但分别与正常妊娠分娩组及及保胎成功分娩组相比,均有统计学意义（P〈0．05）。结论动态监测血清孕酮联合CA125值,能够更准确的预测早期异位妊娠结局。     

妊娠合并心力衰竭的早期识别及治疗

目的：认识妊娠合并心力衰竭对母婴的危险性,探讨早期识别心力衰竭的方法及心力衰竭的治疗原则。方法：回顾分析2002年7月～2008年6月32例在本院诊治的妊娠合并心力衰竭患者的临床资料。结果：妊娠高血压性心脏病占62.5%,风湿性心脏病占9.3%,心肌炎占6.3%,先天性心脏病占6.3%,原因不明占6.3%,红斑狼疮占3.12%。早产儿发生率为37.5%,新生儿窒息占26.7%,孕产妇死亡1例,占3.13%,围生儿死亡占6.25%。结论：妊娠合并心力衰竭的主要病因之一为重度子痫前期,早期诊断心力衰竭及综合治疗妊娠合并心力衰竭,做好孕期保健,有利于降低孕产妇和围生儿的死亡率。     

米非司酮配伍米索前列醇终止剖宫产后早期妊娠疗效分析

目的 研究米非司酮配伍米索前列醇终止剖宫产后早期妊娠的安全性与临床效果。方法选择剖宫产后早期妊娠102例，并将同期自然流产后早孕78例和无分娩史早孕妇女129例作为对照。常规使用米非司酮配伍米索前列醇药物流产方法。记录给药时间、孕囊排出时间、阴道出血量、药物不良反应、术后阴道出血天数、宫腔残留情况及月经恢复情况。结果米非司酮配伍米索前列醇终止剖宫产后早期妊娠、剖宫产后早孕组与自然分娩后早孕组及无分娩史早孕组的孕囊排出时间、完全流产率及月经恢复情况无明显差异，药物流产后阴道流血天数及阴道出血量差别也无显著性意义。结论米非司酮配伍米索前列醇终止剖宫产后早期妊娠安全性及有效性令人满意。     

Serum hormone characterization and exogeneous hormone rescue of bromodichloromethane-induced pregnancy loss in the F344 rat.

Previously, we demonstrated that bromodichloromethane (BDCM), a drinking water disinfection by-product, causes pregnancy loss in F344 rats when given on gestational days (GD) 6-10, encompassing the luteinizing hormone (LH)-dependent period of pregnancy (GD 7-10). Pregnancy loss, i.e., full-litter resorption, was associated with reduced serum progesterone levels; however, we were unable to identify an effect on serum LH. Here, we reevaluated serum LH levels using the more sensitive technique, DELFIA(R). We further sought to better define the temporal pattern of endocrine disruption caused by BDCM during pregnancy with more frequent sampling. Lastly, we attempted to prevent BDCM-induced pregnancy loss using exogenous progesterone or human chorionic gonadotropin (hCG), an LH-agonist. BDCM, in 10% Alkamuls(R), was dosed at 75 mg/kg/day by gavage to F344 rats on GD 6-10 (plug day = GD 0). BDCM-induced pregnancy loss was associated with marked reductions in serum progesterone and LH on GD 10. The decrease in serum LH consistently preceded the decrease in progesterone. In the hormone replacement studies, BDCM and progesterone were administered on GD 6-10, hCG on GD 8-10. BDCM was delivered at 100 mg/kg/day, progesterone at 10 mg/kg twice daily, and hCG at 0.5 IU/0.2 ml/rat. Both progesterone and hCG prevented BDCM-induced pregnancy loss. Thus, BDCM-induced pregnancy loss was associated with marked GD-10 reductions in serum LH and corresponding decreases in progesterone. Furthermore, coadministration of an LH agonist prevented pregnancy loss, supporting the hypothesis that BDCM-induced pregnancy loss in the rat occurs via an LH-mediated mode of action.     

早期妊娠失败药物流产效果的影响因素分析

目的 探讨孕囊大小等因素对早期妊娠失败行药物流产成功率的预测价值.方法 对被诊断为稽留流产和空囊妊娠的患者81例入院后行阴道B超检查,测量胎儿头臀长或孕囊大小,记录已测过的血β-人绒毛膜促性腺激素（β-hCG）水平,将800 μg米索前列醇阴道置药12 ～24 h行阴道B超检查,如果孕囊完整或前后宫腔内膜厚度超过30 mm,再给相同剂量的药物或行清宫术.结果 药物治疗成功32例（39.51％）,为A组;49例（60.49％）药物流产失败行清官术,为B组.两组在年龄、孕周、孕囊大小、流产次数方面无显著差异,而妊娠次数、分娩次数和血β-hCG水平两组有显著差异（P＜0.05）.结论 孕囊大小不作为早期妊娠失败药物流产成功的预测因素,而妊娠、分娩次数及血B-hCG水平会影响药物流产的成功率.     

过期妊娠用缩宫素引产失败后用卡前列甲酯栓的疗效

目的：观察足月妊娠用缩宫素引产失败后再用卡前列甲酯栓的疗效。方法：４６例孕妇，妊娠４１．２±ｓ１．３ｗｋ，年龄２５±ｓ５ａ，无前列腺素药物禁忌证，在用缩宫素引产失败后１０～１２ｈ内，于阴道后穹窿放置卡前列甲酯栓０．３ｍｇ，平卧３０ｍｉｎ，２４ｈ无宫缩再放０．３ｍｇ。结果：４６例中１次用药引产成功３６例，２次用药引产成功１０例，成功率１００％。与同期缩宫素引产成功的８６例相比，诱发宫缩的时间明显缩短，Ｐ＜０．０５。但分娩方式，新生儿出生１ｍｉｎＡｐｇａｒ评分及产后出血量，两者皆无显著差异，Ｐ＞０．０５。结论：缩宫素引产失败后，再用卡前列甲酯栓，效果满意。     

Suppression of decidual cell response induced by dibutyltin dichloride in pseudopregnant rats: as a cause of early embryonic loss

In our previous study, dibutyltin dichloride (DBTCl) caused preimplantation embryonic loss and postimplantation embryonic loss in rats following administration at 7.6 mg/kg and above on Days 0-3 and at 3.8 mg/kg and above on Days 4-7 of pregnancy, respectively. This study was designed to assess the effects of DBTCl on uterine function as a cause of early embryonic loss using pseudopregnant rats. DBTCl was given orally to pseudopregnant rats at 3.8, 7.6 or 15.2 mg/kg on pseudopregnant day (PPD) 0-3 or on PPD 4-7. The decidual cell response was induced by bilateral uterine scratch on PPD 4. The uterine weight on PPD 9 served as an index of uterine decidualization. Uterine weight and serum progesterone levels on PPD 9 were significantly decreased after administration of DBTCl at 7.6 mg/kg and above on PPD 0-3 and PPD 4-7. DBTCl had no effect on the serum estradiol levels and number of corpora lutea. Administration of progesterone reversed the suppression of uterine decidualization in rats given DBTCl on PPD 0-3. It can be concluded that DBTCl suppresses the uterine decidual cell response and decreases progesterone levels, and these effects are responsible for early embryonic loss due to DBTCl exposure.     

药流法、人流法和药物联合人流法终止早孕的效果比较

目的 通过对药流法、人流法和药物联合人流法3种终止早孕的方法进行临床相关指标的分析比较,以探求一种更安全、快捷、高效、痛苦小、副作用少的早孕终止方法。方法 将684例停经49d内的早孕患根据自愿原则分为3组,药流组（A组）241例,采用常规药流法;人流组（B组）220例,采用常规人工负压电宫腔内吸引法;药物联合人流组（C组）223例,术前0.5-2h肛门塞入宫术安全栓1枚,术时操作同B组;并对这3种方法的流产效果、阻道流血量和流血时间、副反应及可接受性等方面进行比较。结果 C组和B组的流产效果较A组好（P＜0.01);C组阴道流血量最少,B组次之,A组最多（P＜0.01);C组和B组的阴道流血时间较A组明显缩短（P＜0.01);B组和C组的术后感染率明显低于A组（P＜0．01）;药物联合人流法更乐于为患接受（P＜0．01）。结论 药物联合人流法更安全、快捷、高效、痛苦小且副反应相对少,更乐于为患接受;药流法在提高流产效果和控制流血量及时间等方面尚须改进。     

高效液相色谱法测定大鼠血浆中的二氯二茂钛

目的 建立反相高效液相色谱法测定大鼠血浆中有机金属抗癌原料药二氯二茂钛的含量.方法 采用Shimadzu VP-ODS色谱柱(250×4.6 mm,5 m),V(甲醇):V(醋酸铵)=55:45,pH 2.5为流动相,流速为1.0 ml/min,紫外检测波长254 nm,柱温室温,氨基比林为内标进行测定.血浆中生物样品采用液-液萃取法进行提取.结果 二氯二茂钛在大鼠血浆中的线性范围为10～120 μg/ml,回归方程为Y=57.83X-0.6042(r=0.9991,n=7),方法精密度RSD为1.8 %(n=6),平均回收率为RSD=1.63%(n=9).结论 方法简单快速,专属性强,可用于测定大鼠血浆中二氯二茂钛的含量,为该类药物的体内血药浓度检测和动力学研究提供了实验依据.     

血清孕酮在鉴别异位妊娠与先兆流产中的意义

目的:探讨血清孕酮对异位妊娠与先兆流产鉴别的意义。方法:选择2004年6月～2005年6月我院住院的异位妊娠患者46例和先兆流产患者56例,检测并比较两组病人血清孕酮值。结果:异位妊娠组的血清孕酮值为(20.83±16.68)nmol/L,显著低于先兆流产组的血清孕酮值(56.22±32.74)nmol/L。两组比较差异有显著性(P<0.05)。结论:血清孕酮的测定可以协助异位妊娠与先兆流产的鉴别诊断。     

Effect of atrazine on implantation and early pregnancy in 4 strains of rats.

Atrazine (ATR) is an herbicide that has been shown to have adverse reproductive effects including alterations in levels of pituitary hormones such as prolactin (prl) and luteinizing hormone (LH) in female LE rats when administered at doses of 200 mg/kg/day for 1 and 3 days. Because the action of prl in promotion of progesterone secretion is essential for the initiation of pregnancy in rats, this study was designed to examine the effect of exposure to ATR during early pregnancy on implantation and short-term pregnancy maintenance. Rats were divided into two groups representing periods of dosing with ATR prior to the diurnal or nocturnal surges of prl. Within each group, four groups consisting of four strains of rats [Holtzman (HLZ); Sprague Dawley (SD); Long Evans (LE); Fischer 344 (F344)] were each further subdivided into four ATR dosages. Rats were dosed by gavage with 0, 50, 100, or 200 mg/kg/day ATR on days 1-8 of pregnancy (day 0 = sperm +). All animals were necropsied on day 8 or 9 of pregnancy. The 200 mg/kg dose of ATR reduced body weight gain in all but one group. Two groups of animals dosed at 100 and 200 mg/kg/day in the nocturnal dosing period showed an increase in percent preimplantation loss, and both of these were F344 rats. HLZ rats were the only strain to show a significant level of postimplantation loss and a decrease in serum progesterone at 200 mg/kg/day both following diurnal and nocturnal dosing. Doses of 100 mg/kg/day also produced postimplantation loss following diurnal and nocturnal dosing, but progesterone levels were decreased only after nocturnal dosing. Alterations in serum LH were seen in several groups. Serum estradiol was significantly increased only in SD rats dosed at the diurnal interval with 200 mg/kg ATR. We conclude that F344 rats are most susceptible to preimplantation effects of ATR and that HLZ rats appear most sensitive to the postimplantation effects of the chemical. LE and SD rats were least sensitive to effects of ATR during very early pregnancy.     

甲氨蝶呤治疗异位妊娠疗效及失败因素的评价

目的 :探讨甲氨蝶呤单次肌肉注射治疗异位妊娠的疗效 ,并分析其治疗失败的相关因素。方法 :对比分析成功组及失败组的临床资料 ,包括停经天数、治疗前 β HCG值、包块直径、腹痛情况、治疗 3d后 β HCG值下降率及包块直径改变情况。 结果 :成功组停经天数平均为 5 3± 5d ,β HCG值平均为14 83± 2 16IU·L-1,包块直径平均为 2 .9± 0 .9cm ;失败组停经天数平均为 6 2± 6d ,β HCG值平均为6 6 6 1± 12 6IU·L-1,包块直径平均为 4 .1± 0 .6cm。成功组有 14 .3%的病人停经天数≥ 6 0d ,11.4 %的病人血 β HCG值≥4 0 0 0IU·L-1,治疗 3d后 β HCG值下降率≤ 15 %的为 14 .3% ,包块直径增加≥2 5 %的为 7.9% ;而失败组各数值分别为 4 0 .0 %、80 .0 %、6 0 .0 %、4 0 .0 %。结论 :甲氨蝶呤是一种有效的治疗早期异位妊娠的药物 ;治疗前的 β HCG值、治疗 3d后 β HCG值下降率及包块直径改变情况与治疗失败关系极大 ;胎心搏动并非为异位妊娠药物治疗的禁忌证。     

青蒿琥酯钠对大鼠抗孕作用的研究

目的 :研究青蒿琥酯钠 (SA)对大鼠的抗孕作用以及其对妊娠及假孕大鼠血清孕酮含量和蜕膜组织的影响 ,以探讨其终止妊娠的机理。方法 :采用放射免疫分析法 (RIA)测定血清孕酮含量 ;HE染色法观察SA对大鼠子宫内膜的影响 ;用人蜕膜细胞体外培养方法观察SA对蜕膜细胞的直接作用。结果 :SA 40mg·kg 1·5d可使妊娠和假孕大鼠血清孕酮水平显著下降 (P<0 .0 5 ) ,但假孕大鼠血清孕酮水平下降晚于妊娠大鼠 ;整体水平能损伤蜕膜组织乃至胎盘 ;对体外培养的人蜕膜细胞有直接杀伤作用 ,其LC50 为 2 5 .18± 3.49ml·L 1。结论 :青蒿琥酯钠能使血清孕酮含量下降并损伤蜕膜和胎盘而使胚胎坏死、吸收而终止妊娠。     

双氯芬酸钾致急性肾衰竭

1名52岁女性类风湿性关节炎患者,给予口服双氯芬酸钾50mg,3次/d,枸橼酸铋钾110mg,3次/d,静脉滴注锝[99mTc]-亚甲基二膦酸盐{[99mTc]-MDP}注射液200mg,1次/d。1周后,患者出现恶心、呕吐、咳嗽、咽痛等症状,Cr由95μmol/L升至542μmol/L,BUN由6.76mmol/L升至18.9mmol/L。遂停药,给予泼尼松龙、左氧氟沙星、血浆置换等治疗,症状无明显缓解,Cr为638μmol/L,BUN为25.8mmol/L。肾穿刺活检结果显示肾淀粉样变性、急性肾小管坏死。经血液透析及对症治疗后,患者病情稳定,Cr降至379～442μmol/L,BUN降至12.3～20.76mmol/L。随访1年,患者肾功能仍未恢复正常。     

新橙皮苷大鼠生育力与早期胚胎发育毒性研究

目的 评价新橙皮苷对大鼠生育力及早期胚胎发育的毒性。方法 200只大鼠（♀♂各半）根据性别和体质量采用分层随机法分成对照（0.5%羧甲基纤维素钠）组、环磷酰胺（20 mg·kg^-1）组、新橙皮苷低、中、高（0.45,0.9和1.8 mg·kg^-1）组。雄鼠于交配前4周开始给药至交配期结束。雌鼠于交配前2周开始给药至妊娠第6天。实验期间每周测定动物体质量。交配结束后,雄性动物对附睾尾精子进行精子检查;妊娠第15天,对雌性动物子宫内容物包括黄体、着床腺、活胎、死胎及吸收胎、胎盘等进行检查。结果 给药期间,各组别动物一般观察均未见明显异常。与对照组相比,各给药组雄鼠交配前体质量、脏器重量、精子计数及精子活力数值未见显著性差异（P>0.05）;对照组和新橙皮苷3个剂量组精子总畸形率均在2%以内。新橙皮苷各给药组雌鼠体质量、脏器重量、黄体数、着床腺、活胎数、吸收胎数、死胎数与对照组相比均无显著性差异（P>0.05）。病理组织学检查结果显示,雄鼠睾丸、附睾、前列腺和精囊腺未见给药相关改变,对照组和新橙皮苷组雌鼠子宫和阴道可见明显孕后变化。结论 新橙皮苷对大鼠生育力及早期胚胎发育未见明显毒性。     

桔梗提取物对D-氨基半乳糖/内毒素诱导暴发性肝衰竭的影响

目的探讨桔梗提取物对D-氨基半乳糖/内毒素诱导的小鼠暴发性肝衰竭的预防作用。方法采用D-氨基半乳糖/内毒素诱导的小鼠暴发性肝衰竭模型,桔梗提取物小剂量组给予桔梗提取物150 mg/kg,桔梗提取物大剂量组给予桔梗提取物300 mg/kg,阳性对照组给予谷胱甘肽300 mg/kg,给药2次。末次给药1 h后除正常组外各组均腹腔注射D-氨基半乳糖(700 mg/kg)和内毒素(10μg/kg),8 h后,颈动脉取血,测定血清中丙氨酸氨基转肽酶(ALT)和天门冬氨酸氨基转移酶(AST)含量,取肝脏,液氮保存。结果模型组小鼠肝损伤严重,ALT、AST较高,给药组AST及ALT降低。结论桔梗提取物能够减轻D-氨基半乳糖/内毒素诱导的小鼠暴发性肝衰竭,对肝脏起到保护作用。