Embryofetal effects of pentamidine isethionate administered to pregnant Sprague-Dawley rats

The effects of pentamidine isethionate on the developing embryo and fetus have not been previously published. Pregnant Sprague-Dawley rats were given various doses of pentamidine during the period of embryogenesis. Animals were killed on days 18 to 20 of pregnancy and their fetuses were removed by hysterectomy. Autopsies were performed on all fetuses. There were significant differences among groups with regard to maternal weight gain and pregnancy resorption. More pregnancy resorptions were noted in the group that received normal human doses (4 mg/kg/day) of pentamidine than in the control group (p less than 0.05). One structural anomaly consisting of unilateral renal agenesis was noted in the 711 fetuses examined. Skeletal survey of fetal rats was unremarkable. Pentamidine was without teratogenic effects in rats when administered in doses similar to those recommended for adult humans; however, it appears to have an embryocidal effect when given in those same doses during embryogenesis.     

Extended administration of the association of zidovudine plus ritonavir during rat pregnancy: maternal and fetal effects

The purpose of the study was to evaluate at term, the effects of the association of zidovudine/ritonavir administered during the entire period of rat pregnancy. Forty pregnant EPM-1 Wistar rats were divided randomly into four groups: one control (drug vehicle control, n=10) and three experimental treated with an oral solution of zidovudine/ritonavir (Exp 1 = 10/20 mg/kg bw, n = 10; Exp 2 = 30/60 mg/kg bw, n=10; Exp 3 = 90/180 mg/kg bw, n=10) from day 0 up to day 20 of pregnancy. Maternal body weights were recorded at the start of the experiment and at the 7th, 14th and the 20th day thereafter. At term (20th day) the rats were anesthetized and, upon laparotomy and hysterotomy, the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed, and the concepts were examined under a stereoscopic microscope for external malformations. The maternal body gain and the mean fetal weight at term were both significantly lower (p < 0.01 and p < 0.0001, respectively) in the experimental groups compared to the control. The recorded resorptions were higher in Exp 2 and Exp 3 groups than in the control group. The other parameters were not affected. The exposure of pregnant rats at term to a 1:2 association of zidovudine plus ritonavir resulted in a significant reduction in maternal body weight gain and increased rate of fetal resorption.     

Short-term exposure of female rats to industrial metal salts: Effect on implantation and pregnancy

Aim: The objective of this study was to characterize the adverse effects of industrial metal salts during the early stages of pregnancy.
Methods: Successfully mated female rats were exposed to the following metal salts via intragastric intubation; manganese sulfate, lead acetate, aluminum chloride, ferrous chloride and ferric chloride in doses of 50 mg/kg body weight and chromium chloride and potassium dichromate in doses of 25 mg/kg body weight on days l–3 or 4–6 of pregnancy. Female rats were killed on day 20 of gestation and the pregnancy outcome was determined.
Results: The administration of manganese sulfate, chromium chloride, potassium dichromate and ferric chloride to female rats on days 1–3 of pregnancy caused pregnancy failure. However, the administration of manganese sulfate and potassium dichromate reduced the number of implantations. The administration of manganese sulfate, potassium dichromate and ferric chloride reduced the number of viable fetuses. The total number of resorptions increased in the lead acetate, aluminum chloride, ferrous chloride and ferric chloride exposed groups. In contrast, the administration of manganese sulfate, aluminum chloride and ferric chloride on days 4–6 of pregnancy caused pregnancy failure. However, the administration of ferric chloride reduced the number of implantations. The administration of manganese sulfate, aluminum chloride, potassium dichromate, ferrous chloride and ferric chloride reduced the number of viable fetuses. The total number of resorptions increased in the manganese sulfate, lead acetate, aluminum chloride, potassium dichromate, ferrous chloride and ferric chloride exposed groups.
Conclusion: This work demonstrates that the short-term exposure of female rats to industrial metal salts during the early stages of gestation would cause failure of pregnancy and produce fetotoxic or fetal resorptive potentials. (Reprod Med Biol 2007; 6 : 179–183)     

Effect of chronic ritonavir administration on pregnant rats and their fetuses

In view of the very important role played by ritonavir in the prevention of maternal-fetal HIV-vertical transmission, the aim of this experimental study was to evaluate its possible effects on several important obstetric parameters. Ritonavir was administered daily to three groups of pregnant rats (E1 = 20 mg/kg; E2 = 60 mg/kg; E3 = 180 mg/kg; n = 10 in every group) from 'zero' up to the 20th day of pregnancy. Controls (n = 10) were injected with the drug vehicle (propyleneglycol) in the same schedule. We evaluated the effects on fetal and maternal weight gain, placental weight, number of implantations and resorptions, malformations, fertility rate, and maternal and fetal death rates. Body weight gain of the E3 group was significantly lower than that of the other groups, most likely due to a toxic effect of the highest dose of ritonavir. Ritonavir did not affect the number of implantations. Group E3 had five resorptions and some reduction in fertility. The mortality rate was significantly affected by ritonavir (2/10 maternal deaths in E2 and 4/10 in E3). On the other hand, no alterations were observed in the fetuses, a finding which could be due at least in part to the protective action of placental P-glycoprotein.     

Comparative effects of quinacrine and erythromycin in adult female rats: a nonsurgical sterilization study

OBJECTIVE: To compare the efficacies of erythromycin and quinacrine for nonsurgical sterilization in rats. Quinacrine used for nonsurgical sterilization in women is mutagenic, and most clinical regimens have had a higher failure rate than surgical sterilization. DESIGN: This acute mammal study included five groups of rats assigned randomly and evaluated at two times after treatment. ANIMAL(S): Adult female Sprague-Dawley rats. INTERVENTION(S): Five groups of female Sprague-Dawley rats (20 per group) were given 70 or 280 mg/kg of erythromycin lactobionate, 350 mg/kg of quinacrine hydrochloride, or vehicle control administered transcervically. Rats were mated 21 days later. Additional groups (n = 4 per group) were treated and killed 21 days later without mating. MAIN OUTCOME MEASURE(S): Fourteen days after mating, numbers of ovarian corpora lutea, total uterine implants, and embryos were evaluated. For unmated animals, uterine sections were examined for fibrosis and lumen closure. RESULT(S): Neither drug altered numbers of corpora lutea. Erythromycin decreased pregnancy rate and number of implantations (increased preimplantation loss) in a dose-related fashion. Quinacrine increased resorptions. Uterine pathology was more extensive and frequent in erythromycin-treated animals, with extent and severity increasing from 21 to 35+ days. CONCLUSION(S): Erythromycin was more effective than quinacrine in preventing pregnancy.     

The effects of intra-amniotic injection of periodontopathic lipopolysaccharides in sheep

OBJECTIVE: Periodontal disease may cause several complications of pregnancy, including fetal death. The purpose of this study was to investigate in sheep the effects of the intra-amniotic injection of lipopolysaccharide from 3 periodontopathic organisms and to compare these effects with those resulting from similar injection of Escherichia coli lipopolysaccharide. The outcomes that were studied included the rates of fetal death and the features of inflammation and lung maturation in survivors. STUDY DESIGN: At 118 days of pregnancy, ewes that were bearing single fetuses were allocated at random to receive intra-amniotic injections of saline solution (n = 13 fetuses), or lipopolysaccharide from Porphyromonas gingivalis (in doses from 0.1 to 10 mg [n = 22 fetuses]), Actinobacillus actinomycetemcomitans (10 mg [n = 6 fetuses]; 1 mg [n = 6 fetuses]), Fusobacterium nucleatum (10 mg [n = 6 fetuses]) or Escherichia coli (10 mg [n = 14 fetuses]; 1 mg [n = 7 fetuses]). Surviving fetuses were delivered abdominally at 125 days of gestation (term, 150 days). RESULTS: When compared with Escherichia coli lipopolysaccharide at similar dosages, periodontopathic lipopolysaccharides had high rates of fetal lethality. Only 6 of 22 fetuses that were exposed to intra-amniotic Porphyromonas gingivalis lipopolysaccharide survived doses of 0.1 to 10 mg, and only 3 of 6 fetuses survived 10-mg Actinobacillus actinomycetemcomitans lipopolysaccharide. Escherichia coli lipopolysaccharide did not cause fetal loss when given at doses of 10 mg (n = 14 fetuses) or 1 mg (n = 7 fetuses). Fetuses that survived exposure to these lipopolysaccharides showed features of inflammation in amniotic fluid and cord blood at birth and enhanced lung maturation. CONCLUSION: Lipopolysaccharides from these 3 periodontopathic organisms have much higher rates of fetal lethality than Escherichia coli lipopolysaccharide but can cause similar intrauterine inflammatory responses and improvements in lung volumes in survivors. Sources of inflammation that are distant from the uterus may underlie a proportion of unexplained stillbirth and other complications of pregnancy.     

Increased nuchal translucency and cystic hygroma in the first trimester: prenatal diagnosis and neonatal outcome

OBJECTIVE: A prospective study of pregnancy outcome in fetuses with increased nuchal translucency above the 95th centile (group NT) or cystic hygroma (group CH) at 10 to 14 weeks of gestation was performed. PATIENTS AND METHODS: Maternal and fetal data (nuchal translucency, caryotype, pregnancy outcome) and infant follow-up of 223 fetuses with first trimester nuchal translucency thickness (183 NT and 40 CH) were analysed. RESULTS: The measurement of nuchal translucency thickness shows a significant difference between group CH and NT (7.4+/-2.9 mm compared 3.7+/-0.8 mm). Chromosomal abnormalities were present in 55% (22/40) in group CH, with 9 cases/22 (40.9%) of Turner syndrome, compared with 14.2% (26/183) in group NT with trisomy 21 in 15 cases/26 (57.7%) (P<0.05). The rate of unfavourable outcome of pregnancy (spontaneous abortion, elective termination of pregnancy, serious structural anomalies) was 80% (32/40) in group CH compared with 18% (33/183) in group NT (P<0.05). In chromosomally normal pregnancies, the rate of fetus with no visible serious structural anomalies was 44.4% (8/18) in group CH compared with 93% (146/157) in group NT (P<0.05). DISCUSSION AND CONCLUSION: Our data show ultrasonographic evaluation of the fetal nuchal translucency thickness at the first trimester is actually indispensable. Neonatal outcome and malformation rate in fetuses with increased nuchal translucency or cystic hygroma are different, even with normal karyotype.     

Maternal immunopotentiation affects the teratogenic response to hyperthermia

Immune responses occurring between the embryo and mother have been shown to influence the embryo's tolerance to teratogens, including chemical teratogens and diabetes-induced teratogenic insult. In this study, we tried to evaluate whether maternal immunostimulation alters the embryo's response to heat shock, one of few teratogens which directly affect the embryo. In order to induce structural anomalies, both intact ICR female mice and mice which had been immunostimulated with xenogeneic rat splenocytes before mating, were exposed to two consecutive exposures to heat (43.6 +/- 0.2 degrees C) for 10 min on day 9 of pregnancy. The number of malformed fetuses, resorptions, and fetal weight were assessed on day 19 of pregnancy. Heat shock-induced apoptosis, and the level of heat shock protein (HSP) 60 expression, were examined in embryonic cells at different time points within 24 h after heating. All these indices differed dramatically in immunized and non-immunized heat shocked females. Heat shocked non-immunized females demonstrated an increased level of resorptions (approximately, 21% versus 8.6% in controls) and the proportion of fetuses with such anomalies as encephalocele and open eyes reached 28% and 21%, respectively. Maternal immunostimulation was associated with a significant decrease in the proportion of fetuses with encephalocele (12.8%), open eyes (8.9%), and resorptions (8%). The maximum level of heat shock-induced apoptosis in cell populations from the embryos of non-immunized females, was approximately, 30% versus 7% in cells of embryos of immunized mice. Heat shock was also followed by a significant increase in HSP60 expression, but only in the cells of embryos of non-immunized females. Together, these findings suggest that the tolerance of mouse embryos to a heat shock-induced teratogenic insult may, to some extent, depend on the character of the maternal immune responses.     

Enhanced glutathione S-transferase (GST) activity in pregnant rats treated with benzo(a)pyrene.

Administration of Benzo(a)pyrene (BP, 50 mg/kg/d) to pregnant rats significantly increased Glutathione S-transferase (GST) activity in placental tissue-extract (Vmax = 40 nmol/min/mg protein and 69 nmol/min/mg protein in controls versus treated animals respectively; P less than 0.01) and total fetal tissue-extract (Vmax = 51 nmol/min/mg protein and 82 nmol/min/mg protein in controls versus treated animals respectively; P less than 0.01) indicating an induction effect of BP on the GST system. An increase in the Km values was also observed: 1.61 x 10(-3) M and 2.84 x 10(-3) M in control versus treated placentae; 1.38 x 10(-3) M and 2.05 x 10(-3) M in control versus treated fetuses. A competitive effect on the enzyme by the BP present in the sample may also be involved. The glutathione content in both tissues did not show any changes after the treatment with BP. This increase in the GST system was not sufficient to protect the fetus. BP affected the reproductive performance of pregnant rats by significantly increasing the number of resorptions and fetal wastage, and, also, by decreasing the fetal weight.     

Effects of low- or high-dose hormone therapy on fasting and post-methionine homocysteine levels in postmenopausal women.

OBJECTIVE: To evaluate the effect of two different hormone therapy (HT) doses on fasting and post-methionine homocysteine levels, an independent risk factor for cardiovascular and thromboembolic diseases. METHODS: Forty-eight women in natural postmenopause randomly received calcium 1 mg/day (control group; n = 12) or calcium plus low dose (1 mg estradiol plus 0.5 mg norethisterone; n = 18) or high dose (2 mg estradiol plus 1 mg norethisterone; n = 18) HT in a 6-month randomized, controlled, prospective study. RESULTS: Folate levels did not vary in any group, while levels of vitamin B12 significantly decreased after low- (-12.2 +/- 6.6%; p < 0.04) or high-dose HT (-13.9 +/- 6.1%; p < 0.01). Fasting homocysteine was reduced by either HT dose in a way that was inversely related to pretreatment homocysteine levels (-0.675x; r = 0.644; p < 0.0001). Modification of post-load homocysteine increase was influenced by the HT dose and inversely related to the homocysteine response to methionine observed at baseline. The regression slope observed with the low-dose HT (-1.637x; r = 0.57; p < 0.02) was significantly steeper (p < 0.001) than that observed with the high-dose HT (-0.304x; r = 0.554; p < 0.03) dose. CONCLUSIONS: Low- or high-dose HT similarly influences fasting homocysteine levels. Low-dose HT seems to be more effective than high-dose HT in reducing the post-methionine homocysteine increase.     

青蒿水提物对小鼠生殖功能及胎鼠生殖发育的影响

目的:观察青蒿水提物对雌性小鼠生殖功能及胚胎发育的影响。方法:80只健康昆明种雌小鼠随机分成4组,实验组连续14 d分别腹腔给予青蒿水提物20 mg/kg(低剂量组)、100 mg/kg(中剂量组)和500 mg/kg(高剂量组),对照组以等量生理盐水代替,然后与雄鼠合笼,同组内一半雌鼠继续给药至交配成功后14 d处死;另一半雌鼠在受精后继续给药35 d,自然分娩,检测青蒿水提物对各组母鼠生育能力和胎仔生长发育的影响。结果:高剂量组青蒿水提物可以使孕鼠的胎仔数以及仔鼠平均体质量、胎盘质量下降,吸收胚胎数增加;但对雌鼠的交配指数、生育指数、活产指数及对出生仔鼠的存活指数、生长指数均无明显影响(P>0.05)。结论:青蒿水提物对孕鼠胚胎有影响,但对雌鼠的其它生殖功能无明显毒性作用。     

Triamcinolone-induced structural alterations in the development of the lung of the fetal rhesus macaque

To test the effect of dose and time on fetal lung maturation by exogenous glucocorticosteroids, triamcinolone acetonide was given to time-mated pregnant rhesus macaques (Macaca mulatta). Triamcinolone acetonide (10 mg/kg or 1 mg/kg) was administered intramuscularly during the midpseudoglandular (63 to 65 days' gestational age) or midcanalicular phase (110 to 112 days' gestational age) of lung development. Fetectomies were performed at 90, 120, or 150 days' gestational age. Nontreated control fetuses and postnatal animals from 59 days' gestational age to 31 days' postnatal age were collected for study of normal developmental lung morphology in the rhesus monkey. Lungs from fetuses of 90 days' gestational age and older were fixed by tracheal infusion, and lungs from fetuses less than 90 days' gestational age were fixed by immersion and embedded for high-resolution light microscopy. Body weight, crown-rump length, and fixed lung volume were determined for all fetuses. Morphometric evaluation of the volume percent of parenchyma, the volume percent of air space and the mean linear intercept as an estimate of air space size was also done. Lungs from fetuses treated during the canalicular phase had thinner, longer, less cellular septa, larger air spaces, and increased numbers of alveolar divisions in terminal air spaces as compared to those of controls. Lungs of fetuses treated during the pseudoglandular phase also had some septa which were thinner, less cellular, and longer than those of controls and had a marked increase in air space size. However, most septa were greatly reduced in height and appeared fewer in number. Alveolar divisions were decreased. The volume percent of air space was larger in all treated groups. Fixed lung volume normalized to body size (body weight and crown-rump length) was greater than that for controls for the high-dose canalicular phase treatment group. The same parameter was lower than that of controls for the high-dose, pseudoglandular phase treatment group of 150 days' gestational age. Body weight and crown-rump length for all pseudoglandular phase triamcinolone acetonide-treated fetuses also tended to be lower than those of controls. We concluded that: (1) there is both a time-dependent and a dose-dependent effect on triamcinolone acetonide on fetal lung maturation in rhesus macaques, (2) triamcinolone acetonide accelerates maturation of the interstitial and epithelial component of the developing fetal rhesus lung independent of age, (3) triamcinolone acetonide accelerates alveolarization only at later treatment ages, and (4) triamcinolone acetonide induces retardation of growth of some of the lung septa and body growth only     

熊去氧胆酸对肝内胆汁淤积孕鼠肝组织中谷胱甘肽、脂质流动性及雌、孕激素受体的影响

目的　探讨熊去氧胆酸对肝内胆汁淤积孕鼠肝组织中谷胱甘肽含量、肝细胞膜脂质流动性以及肝细胞雌、孕激素受体的影响。方法　选择清洁级妊娠SD大鼠 6 0只 ,随机分成 3组 ,每组2 0只 :(1)自妊娠第 13天起 ,正常组孕鼠开始每天皮下注射精制植物油 2 5ml/kg ;对照组和治疗组孕鼠每天皮下注射孕酮 75mg/kg体重和 17 α 乙炔雌二醇 1 2 5mg/kg体重 ,直至孕第 17天。 (2 )自孕第17天起 ,正常组及对照组孕鼠每天行生理盐水 5ml/kg体重灌胃 ;治疗组孕鼠每天行熊去氧胆酸 5 0mg/kg体重灌胃。 (3) 3组孕鼠均于孕第 2 1天处死 ,提取肝组织 ,应用 5 ,5′ 二硫代双直接法测定肝组织中谷胱甘肽含量 ;应用 1,6 二苯已三烯荧光标记法测定肝细胞膜脂质流动性 [以偏振度 (P)的比值表示 ];应用流式细胞技术测定肝细胞雌、孕激素受体 (以平均荧光强度表示 )。结果　 (1)肝组织中谷胱甘肽含量及肝细胞膜脂质流动性比值 :正常组孕鼠分别为 (2 11± 0 0 7)mmol/g蛋白及 0 132±0 0 0 4 ;对照组孕鼠分别为 (1 13± 0 0 3)mmol/g蛋白及 0 14 9± 0 0 0 8;治疗组孕鼠分别为 (1 82± 0 0 4 )mmol/g蛋白及 0 14 1± 0 0 0 6。肝组织中谷胱甘肽含量 ,对照组明显低于正常组 (P <0 0 5 ) ,治疗组高于对照组 ;肝细胞膜脂质     

大豆苷元对去卵巢大鼠血脂及肝脏ERα和LDLR表达的影响

目的:探讨不同剂量大豆苷元对绝经后血脂的保护作用。方法:选用4月龄SD雌性大鼠66只,随机分为:假手术组(Sham)、去势组(OVX)、戊酸雌二醇组(E2)、大豆苷元高剂量(H-Dai,200mg/kg)组、中剂量(M-Dai,50mg/kg)组和低剂量(L-Dai,10mg/kg)组,每组11只。于去势术后4周开始分别给予相应的药物灌胃,3个月后处死大鼠,取血和肝脏,检测血清甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-c)、高密度脂蛋白胆固醇(HDL-c),以及肝脏ERα和LDLRmRNA的表达量。结果:与OVX组相比,大豆苷元可以降低血清LDL-c,且随着剂量的增加其作用更明显(P<0.01);大剂量可以降低血清TG(P<0.05)。大豆苷元还增加肝脏ERα和LDLRmRNA的表达量,且也有剂量依赖效应,低、中剂量组与高剂量组差异显著(P<0.01)。结论:大豆苷元对去势大鼠血脂有一定保护作用,其降低血清LDL-c的作用可能是通过ERα途径增加LDLR的表达而实现的。     

雌二醇用于子痫前期大鼠治疗的研究

目的观察雌二醇用于治疗子痫前期大鼠时,对其血压、尿蛋白含量、白细胞黏附分子CD49d的表达、肿瘤坏死因子α(TNF-α)浓度及新生鼠的影响。方法将30只妊娠大鼠随机分为A、B、C3组,每组10只,于大鼠妊娠第14天,A、B组大鼠尾静脉缓慢滴注内毒素1μg/kg(以2ml生理盐水溶解),建立子痫前期大鼠模型;C组妊娠大鼠用输液泵经尾静脉输注生理盐水2ml,作为对照。从模型建立当天起,B组每天给予17β雌二醇(17β-E2)1mg/kg,肌内注射(17β-E2用无水乙醇溶解,生理盐水稀释)治疗,A、C组每天给予等量生理盐水肌内注射,共6d。分别于治疗前、治疗后的第1、2、5天测量大鼠血压;治疗前及治疗后第2、5天测定大鼠24h尿蛋白含量;于妊娠第20天时终止妊娠,同时采血检测白细胞黏附分子CD49d的表达及TNF-α浓度。结果A组大鼠治疗第5天(妊娠第19天)时,血压为(134.0±2.4)mm Hg(1mm Hg=0.133kPa)、24h尿蛋白含量(0.79±0.10)mg、黏附分子CD49d表达量及TNF-α浓度均增加;B组大鼠治疗第5天时,血压为(123.3±1.7)mm Hg,24h尿蛋白含量为(0.51±0.08)mg,两组血压及24h尿蛋白含量比较,差异均有统计学意义(P<0.05);A组大鼠白细胞黏附分子CD49d的表达强度较C组明显上升,B组较A组白细胞黏附分子CD49d表达强度明显下降,两两比较,差异均有统计学意义(P<0.05)。A组大鼠血浆TNF-α浓度为22.0,C组为11.2,B组为9.3,两两比较,差异也有统计学意义(P<0.05)。B组新生鼠体重较A、C组略有下降,但差异无统计学意义(P>0.05)。结论雌二醇可改善子痫前期大鼠的临床症状,对子痫前期大鼠子代生长发育无明显影响。     

Antepartum diagnosis of noncoiled umbilical cords

OBJECTIVE: The null hypothesis is that fetuses with noncoiled umbilical cords diagnosed in the antepartum period will have outcomes no different from those with normally coiled cords. STUDY DESIGN: We prospectively gathered data from Jan. 1 through May 18, 1992, from all fetuses undergoing routine ultrasonographic evaluation. The outcomes of fetuses noted to have noncoiled umbilical cords were compared with those of a control group of fetuses with normally coiled cords. The control group consisted of those subjects undergoing ultrasonography during the study period who were ultimately transferred to our perinatal practice for the remainder of the pregnancy (i.e., the highest-risk patients). Two outcome parameters were selected for comparison: fetal anomalies and fetal death. RESULTS: Six hundred eighty-seven consecutive ultrasonographic examinations were performed. Twenty-five subjects (3.7%) had noncoiled umbilical cords identified ultrasonographically (mean gestational age at diagnosis 20.3 ± 3.5 [SD] weeks). The control group had 197 subjects. The combined incidence of fetal anomalies or death in the noncoiled group (16%) was significantly greater (p ≤ 0.05, relative risk 4.6 [95% confidence interval 1.41 to 14.15]) than that of the control group (3.5%). The noncoiled group had two fetal deaths (8%), whereas two deaths (1%) occurred among controls (p ≤ 0.05, relative risk 8 [95% confidence interval 1.16 to 50]). Two (8%) fetal anomalies (anencephaly, prune-belly syndrome) occurred in the noncoiled group, whereas the controls (n = 197) had five fetuses (2.5%) with anomalies (not significant). CONCLUSION: The antepartum identification of noncoiled umbilical cords appears to be a risk factor for suboptimal pregnancy outcome. (AM J Obstet Gynecol 1994;170:1729-33.)     

Effect of a traditional herbal medicine, tokishakuyakusan, on the fetal development of the spontaneously hypertensive rat

Forty-three pregnant spontaneously hypertensive rats were administered 1.5% saline and divided into 2 groups: The experimental group of 21 rats and the control group of 22 rats. The animals in the experimental group were administered daily 500 mg/kg of Tokishakuyakusan. No drug was administered to the animals in the control group. Systolic blood pressure measured from 4 to 18 days of pregnancy was similar in both the experimental and control groups. Mean (+/- S.E.) levels of blood viscosity in the experimental group measured on the 19th day of pregnancy were 13.6 +/- 1.6 centipoise (cp) at a shear rate of 0.5/sec and 3.5 +/- 0.1 cp at a shear rate of 230/sec and were significantly lower than those of the control group (19.1 +/- 1.6 cp at 0.5/sec, p less than 0.02; 4.4 +/- 0.2 cp at 230/sec, p less than 0.001). There were observed no significant differences in hematocrit, erythrocyte deformability and fibrinogen levels between two groups. There was observed no significant difference between the mean number in the litter in the 2 groups. The mean weight of the fetuses in the experimental group delivered on the 19th day of pregnancy was 2.4 +/- 0.1 g, being significantly heavier than that of the control group (2.0 +/- 0.0 g) (p less than 0.01). These results indicated that Tokishakuyakusan accelerated development of fetuses of hypertensive rats by utero-placental circulatory improvement which was caused by decreased maternal blood viscosity.     

The effects of cervical application of inhibitors of inducible nitric oxide synthase, cyclooxygenase-1, and cyclooxygenase-2 on delivery in rats

OBJECTIVE: To investigate the effect of cervical application of nonselective and selective inhibitors of nitric oxide synthases--N-nitro-L-arginine methyl ester, L-N-iminoethyl-lysine, and aminoguanidine--as well as inhibitors of cyclooxygenases--indomethacin, and nimesulide--on timing of delivery and fetal death and disease in pregnant rats. STUDY DESIGN: In a series of experimental protocols, timed-pregnant Sprague-Dawley rats (length of pregnancy, 22 days) were randomly allocated to daily cervical applications of (1) 0.04 mg (n = 6), 0.4 mg (n = 6), 4 mg (n = 6), or 40 mg (n = 6) L-N-iminoethyl-lysine or vehicle (n = 12) on days 19 to 22 of pregnancy; (2) 50 mg aminoguanidine (n = 6), 150 mg aminoguanidine (n = 6), or vehicle (n = 10) on days 19 to 22 of pregnancy; (3) 3 mg indomethacin (n = 6) or vehicle (n = 6) on days 19 to 22 of pregnancy; (4) 12.5 mg/kg nimesulide (n = 8), 25 mg/kg nimesulide (n = 8), 50 mg/kg nimesulide (n = 12), or vehicle (n = 12) on days 19 to 22 of pregnancy and 50 mg/kg nimesulide (n = 23) or vehicle (n = 23) on days 14 to 22 of pregnancy; (5) 50 mg/kg nimesulide (n = 10), 50 mg aminoguanidine plus 50 mg/kg nimesulide (n = 10), 50 mg aminoguanidine (n = 10), or vehicle (n = 10) on days 14 to 22 of pregnancy. The following variables were evaluated: proportion of animals that were delivered on day 23, time to delivery of the first pup (midnight on day 22 was considered to be 0 hour), number of stillborn pups, and average pup weight of each litter. RESULTS: Unlike L-N-iminoethyl-lysine, aminoguanidine, and indomethacin, 50 mg/kg nimesulide applied on the cervix daily for 8 days significantly increased the proportion of animals that were delivered on day 23 (18 of 23 versus 7 of 23; P =.003) and the time to delivery of the first pup by a mean of 10.8 hours (P <.001). Shorter treatment with nimesulide for 4 days increased only the time to delivery of the first pup at the 25-mg/kg dosage (P =.008). Simultaneous application of aminoguanidine and nimesulide significantly (P =.008) prolonged pregnancy to a degree similar to nimesulide alone. The experiment with N-nitro-L-arginine methyl ester was aborted because of severe maternal side effects. Unlike pups in the L-N-iminoethyl-lysine, aminoguanidine, and nimesulide groups, significantly more pups in the indomethacin group died in utero compared with the control group (36.1% versus 3.1%; P <.001), and the surviving pups had lower birth weights (P <.001). CONCLUSIONS: In an animal model, nimesulide was effective in delaying the onset of labor, was well tolerated during pregnancy, and affected cervical ripening directly independent of progesterone withdrawal. Conversely, cervical application of nitric oxide synthase and nonselective cyclooxygenase inhibitors do not extend the duration of pregnancy in the dosages studied, and some are associated with significant adverse effects in the mothers and fetuses.     

妊娠早期胎儿颈部透明层厚度与胎儿预后的前瞻性队列研究

目的探讨妊娠早期胎儿颈部透明层(NT)厚度与胎儿预后的关系。方法收集2015年12月至2018年12月于南京大学医学院附属鼓楼医院行妊娠早期胎儿NT厚度测量的单胎孕妇,共4958例建立前瞻性研究队列,进行妊娠早期胎儿结构超声筛查、妊娠早期血清学筛查、妊娠中期超声筛查及对新生儿出生后28 d的体格检查。根据妊娠早期超声筛查的结果,分为胎儿NT增厚(≥3.0 mm)者167例与NT厚度正常者4791例;将胎儿NT增厚的孕妇,分为胎儿单纯NT增厚者86例与NT增厚合并结构异常者81例。分析不同NT厚度胎儿的预后,并重点对单纯NT增厚与NT增厚合并结构异常胎儿的妊娠结局进行分析。妊娠早期超声筛查发现胎儿结构异常或血清学筛查结果为高风险的孕妇,经绒毛穿刺取样术行染色体微阵列分析(CMA)检测以明确产前诊断。结果(1)胎儿NT厚度正常孕妇的妊娠结局:共4791例孕妇,包括胎儿NT厚度正常且无结构异常者4726例,其中妊娠中期及产后新诊断结构异常83例,4688例活产;胎儿NT厚度正常但结构异常的孕妇65例,其中61例孕妇终止妊娠,4例活产。(2)胎儿单纯NT增厚孕妇的妊娠结局:86例孕妇中,66例(76.7%,66/86)行CMA检测,3例胎儿诊断为21三体综合征;除7例孕妇选择终止妊娠外,余79例行妊娠中期超声检查、新生儿出生后28 d体格检查、新生儿电话随访至6~21个月均未发现发育异常。(3)胎儿NT增厚合并结构异常孕妇的妊娠结局:81例孕妇中,73例(90.1%,73/81)行CMA检测,其中32例的胎儿为染色体非整倍体异常。70例选择终止妊娠,2例妊娠中期自然流产,9例活产。(4)NT增厚是否合并结构异常胎儿的产前诊断结果及预后比较:单纯NT增厚的胎儿染色体非整倍体的发生率为3.5%(3/86),合并结构异常者为39.5%(32/81),两者比较,差异有统计学意义(χ2=32.7,P<0.01);胎儿单纯NT增厚孕妇的健康新生儿存活率为91.9%(79/86),合并结构异常者为9.9%(8/81),两者比较,差异有统计学意义(χ2=112.3,P<0.01)。结论妊娠早期,超声筛查胎儿NT及结构,能提高出生缺陷的产前筛查率。单纯NT增厚胎儿的染色体非整倍体的发生率较低,新生儿健康存活率较高。