抗心磷脂抗体阳性复发性流产患者妊娠前后凝血功能动态变化的研究

目的探讨抗心磷脂抗体阳性复发性流产患者妊娠前后凝血功能的动态变化。方法选取2010年1月至2012年1月在中山大学附属中山市人民医院就诊复发性流产患者,抗心磷脂抗体阳性患者46例为研究对象。选取同期就诊的抗心磷脂抗体阴性复发性流产患者23例及健康孕前检查妇女23例做为对照组。分别在患者计划妊娠时月经干净后3d、首次早早孕试验阳性当天及此后2周采血测定凝血功能指标。结果抗心磷脂抗体阳性复发性流产患者妊娠前与对照组比较vWF和TF升高(P<0.01);早早孕时与对照组和孕前比较vWF、TF、FPA及D-二聚均升高(P<0.01);早孕时与对照组和孕前比较vWF、TF、FPA及D-二聚体均升高(P<0.01),APTT降低(P<0.01)。结论抗心磷脂抗体阳性复发性流产患者孕前即存在病理性高凝状态,妊娠后这种高凝状态进行性加重,呈动态变化过程。     

肝素联合阿司匹林治疗复发性流产的疗效探讨

目的探讨肝素联合阿司匹林治疗因抗心磷脂抗体所致复发性流产的临床疗效。方法选择我院2004年3月～2007年3月因抗心磷脂抗体阳性所致复发性流产的患者15例,行阿司匹林联合肝素综合治疗,观察妊娠结局。结果妊娠成功率为80.0%(12/15),无妊娠并发症发生,母婴妊娠结局良好。结论肝素联合阿司匹林对抗心磷脂抗体阳性所致复发性流产的治疗是安全、有效的。     

阿司匹林与激素类药物联合治疗抗心磷脂抗体阳性早孕复发性流产的临床价值

目的:探讨阿司匹林联合激素类药物治疗抗心磷脂抗体阳性早孕复发性流产的疗效,为优化抗心磷脂抗体阳性早孕复发性流产治疗方案提供依据。方法:选择2012年8月—2013年8月收治的早孕复发性流产患者72例。在保障患者知情权的基础上,根据患者自愿分为观察组和对照组,各36例。在确定妊娠到妊娠3个月期间,对照组肌肉注射绒毛膜促性腺激素每日1 000~2 000 U。观察组在对照组的基础上,在确定妊娠后,口服阿司匹林和泼尼松直至抗心磷脂抗体监测连续两次阴性停止服药。随访1年,了解患者妊娠情况和分娩结局。结果:观察组痊愈、有效和无效例数分别有26,3和7例,痊愈率和总有效率为72.2%和80.6%,痊愈率和总有效率显著高于对照组(χ2分别为19.835和18.627,P<0.05)。观察组恶心、腹痛、头痛、疲倦、过敏性皮疹分别有1,0,0,2,1例,不良反应发生率为11.1%,与对照组相比差异无统计学意义(χ2=2.567,P>0.05)。观察组完全依从、基本依从和不依从例数分别为28,6和2例,依从率为94.4%。观察组治疗依从率显著高于对照组(χ2=6.203,P<0.05)。结论:抗心磷脂抗体阳性早孕复发性流产患者在绒毛膜促性腺激素治疗基础上,行阿司匹林联合激素类药物治疗可以提高妊娠的成功率,改善妊娠结局,避免流产、早产,获得更好的治疗依从性,在临床中具有重要的运用价值。     

对病理妊娠中抗心磷脂抗体阳性孕妇服用复方丹参片的妊娠结局分析

目的了解复方丹参片对病理妊娠中抗心磷脂抗体阳性孕妇的治疗效果。方法将198例病理妊娠中抗心磷脂抗体阳性的孕妇随机分为用药组和对照组,对二者的妊娠结局进行统计学分析。结果用药组的足月分娩率比对照组显著升高(P<0.01);对照组的早产、流产率、妊娠高血压疾病的发生率和胎儿丢失率均比用药组显著升高(P<0.01)。结论在病理妊娠中,抗心磷脂抗体阳性者必须治疗;复方丹参片作为基础药物使用后,可显著提高足月分娩率,降低早产、流产率、妊娠高血压疾病的发生率和胎儿丢失率。抗心磷脂抗体可能会随着病情变化从阴转阳,或反复出现。     

抗HLA-I/II抗体、抗心磷脂抗体和抗β2糖蛋白1抗体与不孕和流产的关系

目的探讨抗HLA-I/II抗体、抗心磷脂抗体（ACA）和抗β2糖蛋白1（β2GP1）抗体与不孕和流产的关系。方法选取2011～2012年在本院就诊的不孕症患者550例、复发性流产患者1650例和正常分娩者150例。对各组分别进行抗HLA-I/II抗体、抗心磷脂抗体和抗β2GP1抗体检测,并将阳性率进行比较。结果不孕组抗HLA-I/II阴性率、ACA和抗β2GP1阳性率分别为76.0%、19.3%和17.5%;RSA组抗HLA-I/II阴性率、ACA和抗β2GP1阳性率分别为85.0%、23.5%和22.7%;均显著高于对照组,P〈0.05。结论抗HLA-I/II抗体、抗心磷脂抗体和抗β2GP1抗体是引起不孕和复发性流产的重要因素。     

抗磷脂综合征在复发性流产中的研究进展

抗磷脂综合征(APS)是一组由抗磷脂抗体(aPLs)引起的血栓形成或不良妊娠结局的临床综合征。我国把与同一配偶连续发生2次或2次以上妊娠28周前的胎儿丢失定义为复发性流产(RSA)。APS能引起严重的产科并发症,RSA就是APS女性常见的临床症状。本文对APS的诊断、引起RSA的机制及治疗作一综述。     

补肾活血方治疗抗心磷脂抗体阳性复发性流产疗效观察

目的：观察补肾活血方与阿司匹林治疗抗心磷脂抗体阳性所致复发性流产的疗效。方法76例血清抗心磷脂抗体阳性复发性流产的孕妇随机分为治疗组和对照组,治疗组服用补肾活血中药,对照组服用阿司匹林,两组均口服黄体酮胶囊,肌注绒促性素至孕84d。结果治疗组有效率为84.2%,对照组有效率为76.3%,P=0.014(<0.05),差异有统计学意义。结论补肾活血方治疗抗心磷脂抗体阳性所致复发性流产的疗效优于阿司匹林。     

溶血磷脂酸与抗心磷脂抗体联合检测在妊高症患者中的临床意义

目的 探讨溶血磷脂酸（lysophosphatidic acid,LPA）与抗心磷脂抗体（anti-cardiolipin antibody,ACA）联合检测预测妊高症疾病发展及妊娠结局的价值.方法 分别采用生化法、酶联免疫法测定142例妊高症患者（其中妊娠期高血压53例,轻度子痫前期46例,重度子痫前期43例）及正常妊娠晚期孕妇（对照组58例）血浆LPA水平及抗心磷脂抗体阳性率,分析两者在不同程度妊高症患者中的差异及相关性,同时评价其与妊娠预后的关系.结果 妊高症患者血浆LPA水平随病情发展依次升高,且均高于对照组（P＜0.05）;重度妊高症组抗心磷脂抗体阳性率高于其他组（P＜0.05）.重度妊高症患者抗心磷脂抗体阳性组血浆LPA水平明显升高,且发病孕周小,围产儿体重低,新生儿Apgar评分低,与阴性组比较,差异均有统计学意义（P＜0.05或0.01）.结论 妊娠期高血压疾病病情程度与血浆LPA水平相关,病情越重,LPA水平也越高.抗心磷脂抗体与重度妊高症的发病有关.LPA与ACA联合检测可早期预测妊高症的病情程度及妊娠结局,有望成为病情监测及预后判断的指标.     

120例剖宫产术后早期妊娠妇女的药物流产结局分析

目的 对120例剖宫产术后早期妊娠妇女药物流产后的结局进行分析.方法 收集在本院妇产科门诊采用药物流产终止妊娠的120例剖宫产术后早期妊娠妇女(观察组)和50例正常早孕妇女(对照组).根据观察组药物流产结局分为成功组(A组)和失败组(B组),回顾性分析其的临床资料,分析导致两组流产结局不同的原因.结果 与对照组(6.0％)比较,观察组药物流产失败率(18.3％)明显增加(x 2=4.283,P＜0.05);观察组药物流产后腹痛、阴道出血时间过长和出血量过多的发生率均较对照组高,但差异均无统计学意义(均P＞0.05);观察组中A、B两组妊娠次数(t=6.600,P＜0.05)、孕周(t =5.061,P＜0.05)、囊胚最大径(t=21.325,P＜0.05)、盆腔炎症(t=14.582,P＜0.05)、子宫位置(t =13.486,P＜0.05)比较,差异均有统计学意义.结论 剖宫产术后早期妊娠妇女应用药物流产失败率明显增高,妊娠次数、孕龄、囊胚最大径、盆腔炎症、子宫位置等均可能与流产失败有关.     

肝素治疗反复妊娠丢失伴抗磷脂抗体阳性孕妇的疗效观察

目的探讨肝素治疗因抗磷脂抗体所致反复性妊娠丢失及对孕妇血液中抗体的影响。方法记录门诊接诊的狼疮抗凝抗体（LA）和/或抗心磷脂抗体（ACA）阳性的反复性妊娠丢失患者（排除遗传、感染、内分泌及子宫附件异常等可导致流产的因素）,选取54例再次妊娠患者,前瞻性的随机分为两组,各27例,分别予肝素（肝素组）和强的松加小剂量阿司匹林（对照组）治疗,观察比较两组的妊娠结局和治疗后LA和ACA的量。结果肝素组27例,足月产27例,早产4例,流产2例,活产率92.6%,抗体清除率71.4%。对照组27例,足月产13例,早产8例,流产6例,活产率77.8%,抗体清除率35.7%。活产率差异无显著性（P〉0.05）,抗体清除率差异有统计学意义（P〈0.01）。结论肝素对抗磷脂抗体所致的反复妊娠丢失治疗效果肯定,并能有效清除抗磷脂抗体。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.