The effect of sildenafil on the altered thoracic aorta smooth muscle responses in rat pre-eclampsia model

The pathophysiology of pre-eclampsia is still unknown thus effective primary prevention is not possible at the stage. The present study was conducted to research the smooth muscle responses in the pre-eclampsia model with suramin treated rats and the effect of phosphodiesterase-5 (PDE5) inhibitor on these responses. Rats of three groups; control, suramin and suramin+sildenafil were given intraperitoneal injections of saline, suramin or sildenafil citrate. Suramin injections caused increased blood pressure, protein in urine and caused fetal growth retardation. The use of sildenafil citrate straightened significantly both blood pressure and average fetus weight, but did not reach to control values. At the end of pregnancy, thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction responses, sodium nitroprusside and papaverine relaxation responses were similar in three groups. Contraction responses of phenylephrine, increased significantly in suramin group. Relaxation responses of acethylcholine and bradykinin decreased in suramin group. The use of sildenafil citrate partially straightened both relaxation and contraction responses, but did not reach to control values. In all groups in the presence of L-nitromonomethylarginine (L-NAME), 1H-(1, 2, 4) oxadiazole (4, 3-a) guinoxalin-1-one (ODQ) and indomethacin decreased the relaxation responses of acetylcholine and bradykinin. The cyclic guanosine monophosphate (cGMP) content of thoracic aorta tissue was determined by radioimmunoassay technique. The content of cGMP in suramin group decreased and use of sildenafil citrate increased the cGMP content but did not reach to control values. We conclude that in pre-eclampsia, the increase of contraction responses, the decrease of relaxation responses and the decrease of cGMP content can depend on insufficiency about synthesis or release of relaxant factors which was released from the vessel endothelium. The results in this study show that in pre-eclampsia; PDE5 inhibitors enhance endothelial function and may be used for protection. Further studies are needed to clear the efficiency and safety of PDE5 inhibitors.     

Incidence of atrial fibrillation in pregnancy and clinical significance: A meta-analysis

PurposeAtrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide, and is associated with increased morbidity and mortality. However, the incidence and maternal/fetal outcomes of AF in pregnancy remain unclear. This study’s aims were to investigate the pooled incidence of AF in pregnant women and to assess maternal/fetal outcomes of AF in pregnancy.Material and methodsA literature search for studies that reported incidence of AF in pregnancy, was conducted using MEDLINE, EMBASE and Cochrane Database from inception through May 2018. Pooled incidence with 95%CI were calculated using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018095955).ResultsWe identified 7 cohort studies including 301,638 pregnancies. The pooled estimated incidence of AF in pregnancy among women with no known heart disease, and those with structural heart disease was 0.3% (95%CI: 0.01%–40.6%) and 2.2% (95%CI: 0.96%–5.01%), respectively. Among women with known AF, the pooled estimated incidence of recurrent AF in pregnancy was 39.2% (95%CI: 16.9%–67.2%). The pooled estimated incidence of pre-eclampsia and congestive heart failure among pregnant patients with AF was 4.1% (95%CI: 2.1%–7.8%) and 9.6% (95%CI: 5.7%–15.9%), respectively. The pooled estimated incidence of fetal events including premature birth, small for gestational age, respiratory distress syndrome, intraventricular hemorrhage, death was 26.6% (95%CI: 20.4%–34.0%).ConclusionThe overall estimated incidence of AF and recurrent AF during pregnancy is as high as 2.2% and 39.2%, respectively. AF during pregnancy may result in poor maternal and fetal outcomes.     

早发型重度子痫前期分娩前后CD28/CTLA-4的相关研究

目的:探讨白细胞分化抗原28/细胞毒性T淋巴细胞相关抗原4(CD28/CTLA-4)与早发型重度子痫前期发病的关系。方法:采用流式细胞技术分别测定30例早发型重度子痫前期患者分娩前后的CD28、CTLA-4、CD28/CTLA-4表达水平,同时测量各组受试者血压及肝肾功能。结果:早发型重度子痫前期患者分娩前CD3+CD4+CTLA-4+、CD3+CD8+CTLA-4+高于分娩后,CD3+CD4+CD28+/CD3+CD4+CTLA-4+、CD3+CD8+CD28+/CD3+CD8+CTLA-4+低于分娩后,差异有统计学意义(均P0.05)。CD3+CD4+CD28+/CD3+CD4+CTLA-4+、CD3+CD8+CD28/CD3+CD8+CTLA-4+两者无直线相关性(r=-0.037,P=0.844)。结论:早发型重度子痫前期患者分娩后较分娩前CTLA-4的表达下降,CD28/CTLA-4上升,可能提示CD28/CTLA-4免疫偏移与子痫前期的发生有关。     

晚期糖基化终产物与子痫前期的研究进展

晚期糖基化终产物（advanced glycation end products,AGEs）是指蛋白质、核酸、脂质等大分子物质的氨基在无酶条件下生成的一组稳定的终末产物,既可直接损伤细胞,也能通过与受体结合发挥生物学效应。研究发现,AGEs与线粒体氧化应激损伤及脂质代谢紊乱关系密切。子痫前期是妊娠期特有的疾病,是孕产妇和围生儿患病及死亡的主要原因,但具体发病机制未明,现普遍认为线粒体氧化应激损伤及脂质代谢紊乱参与子痫前期发病。就AGEs在子痫前期发病中的作用进行综述。     

Maternal outcomes of hypertensive disorders in pregnancy at Korle Bu Teaching Hospital,Ghana

Objective

To determine maternal outcomes of hypertensive disorders in pregnancy at Korle Bu Teaching Hospital (KBTH) in Accra, Ghana.

Methods

A cross-sectional study was conducted between January 1 and February 28, 2013. All women delivering at KBTH whose pregnancies were complicated by hypertensive disorders were identified. A structured questionnaire was administered, and the women were followed up on a daily basis until discharge from hospital. Medical records were also reviewed to identify any complications of hypertensive disorders.

Results

A total of 368 women were analyzed. Of 10 maternal deaths, 3 (30.0%) were due to hypertensive disorders in pregnancy, and specifically pre-eclampsia. Overall, 168 (45.7%) women with hypertensive disorders in pregnancy delivered by cesarean, 16 (4.3%) had placental abruption, 11 (3.0%) had pulmonary edema, 3 (0.8%) had HELLP syndrome, 2 (0.5%) had acute renal failure, 3 (0.8%) had an intracerebral hemorrhage or cerebrovascular accident, 21 (5.7%) were admitted to the intensive care unit, 7 (1.9%) had disseminated intravascular coagulation, and 58 (15.8%) had eclampsia. Cesarean delivery, admission to intensive care unit, and eclampsia were significantly more common in women with pre-eclampsia than in those with other hypertensive disorders.

Conclusion

Hypertensive disorders in pregnancy are associated with high incidences of adverse maternal outcomes in Ghana, with significantly increased frequencies in women with pre-eclampsia.     

Th1/Th2平衡调控对妇产科疾病影响的研究进展

近年来研究发现辅助性T细胞1型（Th1）/Th2的平衡调控与妇产科疾病的发生、发展、治疗和转归有密切的关系。Th1细胞调节细胞免疫,主要促进炎症反应和细胞毒性活动;Th2细胞调节体液免疫,主要刺激细胞的分化与增殖。Th1细胞通过合成γ干扰素（IFN-γ）抑制Th2细胞功能,Th2细胞通过合成白细胞介素4（IL-4）抑制Th1细胞的功能,二者相互作用、相互调节。正常妊娠情况下Th1/Th2细胞应答存在生理性失衡,母体Th2型细胞因子抑制Th1型细胞因子的产生,这种生理性失衡被破坏可导致复发性流产、早产、子痫前期及不孕症等妊娠相关疾病。而宫颈癌、卵巢癌、子宫内膜异位症等妇科疾病与Th1/Th2平衡调控有关,但其确切免疫学机制尚不明确,尚需进一步深入研究,以期为多种妇产科疾病的免疫学治疗开辟新的前景。     

Obstetrical outcome in women with endometriosis including spontaneous hemoperitoneum and bowel perforation: a systematic review

Increasing evidence suggests that pregnant women with endometriosis have a higher risk of adverse obstetrical complications. The aim of this study was to systematically review the existing literature on this aspect. A PubMed/MEDLINE search was performed from its inception until September 2017 for studies on adverse obstetrical complications in pregnant women with endometriosis, including: preeclampsia, preterm birth, small for gestational age (SGA), antepartum hemorrhage, spontaneous hemoperitoneum, spontaneous bowel perforation, preterm birth, cesarean delivery, stillbirth and postpartum hemorrhage. Overall, the results showed an increased risk of preterm delivery, antepartum hemorrhage, delivery by cesarian section, and the rare complications of spontaneous hemorrhage in pregnancy and spontaneous bowel perforation. There is no firm evidence for any increased risk of preeclampsia, having a child born small for gestational age, stillbirth, or postpartum hemorrhage. In conclusion, pregnant patients with endometriosis should be offered special clinical attention.     

葡萄糖酸钙联合卡前列素氨丁三醇对子痫前期产妇剖宫产后出血的临床疗效研究

目的：探讨葡萄糖酸钙联合卡前列素氨丁三醇对子痫前期产妇剖宫产后出血的临床疗效。方法：选取2016年9月-2017年9月我院产科收治的160例子痫前期以剖宫产终止妊娠的产妇为研究对象,按照随机数字表法分为研究组和对照组,各80例。在胎儿娩出后,对照组给予缩宫素和卡前列素氨丁三醇,研究组在对照组的基础上加用葡萄糖酸钙。比较2组产妇手术过程中、手术结束后2 h和手术结束后24 h的出血量、产后出血率、剖宫产前后血清Ca2＋浓度和血红蛋白含量,以及用药后不良反应发生率。结果：2组产妇手术过程中的出血量比较差异无统计学意义（P＞0.05）;手术结束后2 h和24 h,研究组的出血量均少于对照组,差异有统计学意义（均P＜0.05）。研究组产后出血率为15.00%（12/80）,对照组产后出血率为36.25%（29/80）,差异有统计学意义（χ2=9.477,P=0.002）。剖宫产后,2组产妇血清Ca2＋浓度均比剖宫产前升高（均P＜0.05）,血红蛋白含量均比剖宫产前降低（均P＜0.05）。用药后不良反应发生率研究组（16.25%）和对照组（13.75%）比较差异无统计学意义（χ2=0.196,P=0.658）。结论：葡萄糖酸钙联合卡前列素氨丁三醇用于预防子痫前期产妇剖宫产的产后出血具有更好的止血效果且安全,值得临床推广。     

P27基因参与子痫前期发生机制的研究进展

子痫前期(pre-eclampsia,PE)是妊娠期特发疾病,其发生与发展是导致母儿患病率、死亡率增加的重要原因,胎盘中滋养细胞正常的增殖、迁移与分化与其关系密切。P27作为细胞周期蛋白依赖性激酶抑制剂(cyclin dependent kinase inhibitors,CKIs),与细胞周期因子结合调控细胞周期。与正常孕妇相比,PE患者胎盘滋养细胞中P27基因的表达明显增加,这可能与滋养细胞的增殖及侵入障碍有关。P27蛋白与不同蛋白质结合发挥不同作用,其调节主要依靠翻译后修饰及亚细胞定位。Nodal作为转化生长因子β(transforming growth factor β,TGF-β)的成员,在滋养细胞中通过多种机制上调P27 mRNA和蛋白水平,提高了P27蛋白的稳定性并在S10处诱导了P27蛋白的磷酸化,促使P27蛋白和CDK2向细胞质的转移,且加强P27/CDK2/CDK5/Stathmin的结合,从而抑制了细胞增殖、迁移及侵袭。P27蛋白在许多位点被磷酸化,氧化应激、蛋白激酶B(protein kinase B,Akt)、蛋白O-岩藻糖基转移酶1(protein O-fucosyltransferase 1,poFUT1)、磷酸果糖-2-激酶/果糖-2,6-二磷酸酶(PFKFB1-4)等通过使P27蛋白磷酸化,影响其泛素-蛋白酶体降解途径调节细胞周期进程。