改善血栓形成新的药物组合物及其分子机制

目的：研究α1受体阻断药与山莨菪碱（Ani）形成的药物组合物改善血栓形成的作用及其分子机制。方法：离体大鼠尾动脉血管模型研究α1受体阻断药及其与山莨菪碱的药物组合物的扩血管效应,角又菜胶诱发小鼠尾部血栓模型研究组合物对抗血栓形成的作用及其机制。结果：α1受体阻断药中哌唑嗪（Pra）对血管环舒张率最大,达（82．6±8．9）％,作用强度最强,Ec50值为O．44μmol/L;山莨菪碱和哌唑嗪分别以不同剂量配伍组成组合物,能使角叉菜胶诱发的鼠尾血栓长度（啪）由24．6±4．6缩短到6．94-2．7,成栓率由86．6％下降到50．0％。上述新药物组合物能显著延长血栓小鼠血浆凝血酶原时间（er）,对活化部分凝血活酶时间（APTT）无影响;能抑制血栓小鼠血浆中组织型纤溶酶原激活剂（t-PA）、6-酮一前列腺素F1a（6．Keto．PGF1α）含量的降低和组织纤溶酶原激活剂抑制物-1（PAI-1）、血栓烷B2（TXB2）的增多;并不在于扩血管作用的进一步增强上。结论：山莨菪碱和哌唑嗪组成的药物组合物具有舒张外周血管和改善血栓形成的作用,其抗血栓形成机制分别与影响外源性凝血途径、抑制血小板的活化功能以及促进纤溶功能有关。     

Increased risk of venous thrombosis by AB alleles of the ABO blood group and Factor V Leiden in a Brazilian population

Most cases of a predisposition to venous thrombosis are caused by resistance to activated protein C, associated in 95% of cases with the Factor V Leiden allele (FVL or R506Q). Several recent studies report a further increased risk of thrombosis by an association between the AB alleles of the ABO blood group and Factor V Leiden. The present study investigated this association with deep vein thrombosis (DVT) in individuals treated at the Hemocentro de Pernambuco in northeastern Brazil. A case-control comparison showed a significant risk of thrombosis in the presence of Factor V Leiden (OR = 10.1), which was approximately doubled when the AB alleles of the ABO blood group were present as well (OR = 22.3). These results confirm that the increased risk of deep vein thrombosis in the combined presence of AB alleles and Factor V Leiden is also applicable to the Brazilian population suggesting that ABO blood group typing should be routinely added to FVL in studies involving thrombosis.     

白藜芦醇苷对血栓形成及血浆TXB2和6-keto-PGF1α水平的影响

研究了白藜芦醇苷(polydatim,PD)的抗血栓形成作用及其作用机制。采用小鼠尾静脉注射花生四烯酸(arachidonicacid,AA)、电刺激大鼠颈动脉血栓形成方法评价PD的抗血栓形成作用;运用放射免疫法测定polydatin对兔血浆血栓素B2(thromboxaneB2,TXB2)及6酮前列腺素F1α(6ketoprostaglandinF1α,6ketoPGF1α)水平的影响。结果显示PD对AA、电刺激大鼠颈动脉引起的血栓形成具有明显的对抗作用;PD亦能降低兔血浆TXB2含量并升高6KetoPGF1α水平。本实验提示PD有明显的抗血栓形成作用,其机制可能与其降低血浆TXB2含量及升高6KetoPGF1α水平密切相关。     

患肢加压溶栓治疗下肢深静脉血栓形成的临床疗效及护理效应

目的:探讨止血带结扎患肢,从足背浅静脉推注尿激酶治疗下肢深静脉血栓形成的临床疗效及护理效应。方法:对62例下肢深静脉血栓患者经患肢足背静脉穿刺,踝关节上用止血带阻断浅静脉后,推注中等剂量尿激酶.通过测量腿围和彩超结果来评价是否有效。并采用多种护理辅助手段辅助治疗。结果:临床症状迅速改善,有效率22.5%,显效率77.5%。结论:此方法操作简单,所用材料价格便宜,临床效果明显,值得推广应用。     

股神经阻滞和收肌管阻滞对全膝关节置换术后下肢静脉血栓形成的影响

目的:探究股神经阻滞(femoral nerve block,FNB)和收肌管阻滞(adductor canal block,ACB)对全膝关节置换术(total knee arthroplasty,TKA)后下肢静脉血栓形成的影响。方法:将2019年3月-2019年4月拟在全身麻醉下行全膝关节置换术的40例患者随机分为FNB组和ACB组,所有患者均给予超声引导下单次注射,术后均给予标准化抗凝治疗。术后评估两组患者不同时间节点的疼痛评分、股四头肌肌力及术后下肢静脉血栓形成情况。结果:两组患者术后2、6、12、24、48、72 h患肢术区局部疼痛的VAS评分差异无统计学意义(P0.05)。ACB组患者术后2、6、12、24、48 h股四头肌肌力均明显高于FNB组(P0.05),术后72 h两组患者股四头肌肌力无明显差异(P0.05)。ACB组在术后患者首次直腿抬高时间(4.5±4.6)h,显著低于FNB组在术后患者首次直腿抬高时间(25.6±12.6)h,两组对比差异有统计学意义(P0.05)。术后72 h给予两组患者复查双下肢血管超声,复查结果显示,FNB组19例患者中共有2例出现下肢静脉血栓,均为肌间隙静脉血栓形成;ACB组20例患者中无患者出现下肢静脉血栓形成,差异无有统计学意义(P0.05)。结论:FNB与ACB在全膝关节置换术后镇痛方面无明显差异,但ACB组较好的保留患者术后早期股四头肌肌力,对于术后功能锻炼和快速康复有较积极的作用,两种神经阻滞方式对患者VTE风险的影响相同。     

Long‐term mTOR inhibitors administration evokes altered calcium homeostasis and platelet dysfunction in kidney transplant patients

The use of the mammal target of rapamycin (mTOR) inhibitors has been consolidated as the therapy of election for preventing graft rejection in kidney transplant patients, despite their immunosuppressive activity is less strong than anti‐calcineurin agents like tacrolimus and cyclosporine A. Furthermore, as mTOR is widely expressed, rapamycin (a macrolide antibiotic produced by Streptomyces hygroscopicus) is recommended in patients presenting neoplasia due to its antiproliferative actions. Hence, we have investigated whether rapamycin presents side effects in the physiology of other cell types different from leucocytes, such as platelets. Blood samples were drawn from healthy volunteers and kidney transplant patients long‐term medicated with rapamycin: sirolimus and everolimus. Platelets were either loaded with fura‐2 or directly stimulated, and immunoassayed or fixed with Laemmli's buffer to perform the subsequent analysis of platelet physiology. Our results indicate that rapamycin evokes a biphasic time‐dependent alteration in calcium homeostasis and function in platelets from kidney transplant patients under rapamycin regime, as demonstrated by the reduction in granule secretion observed and subsequent impairment of platelet aggregation in these patients compared with healthy volunteers. Platelet count was also reduced in these patients, thus 41% of patients presented thrombocytopenia. All together our results show that long‐term administration of rapamycin to kidney transplant patients evokes alteration in platelet function.     

Seasonal Variation in Occurrence of Pulmonary Embolism: Analysis of the Database of the Emilia‐Romagna Region,Italy

Seasonal variation in the occurrence of cardiovascular and cerebrovascular events, including pulmonary embolism (PE), has been reported; however, recent large‐scale, population‐based studies conducted in the United States did not confirm such seasonality. The aim of this large‐scale population study was to determine whether a temporal pattern in the occurrence of PE exists. The analysis considered all consecutive cases of PE in the database of all hospital admissions of the Emilia Romagna region in Italy at the Center for Health Statistics between January 1998 and December 2005. PE cases were first grouped according to season of occurrence, and the data were analyzed by the χ² test for goodness of fit. Then, inferential chronobiologic (cosinor and partial Fourier) analysis was applied to monthly data, and the best‐fitting curve for the annual variation was derived. The total sample consisted of 19,245 patients (8,143 male, mean age 71.6±14.1 yrs; 11,102 female, mean age 76.1±13.7 yrs). Of these, 2,484 were <65 yrs, 5,443 were between 65 and 74, and 11,318 were ≥75 yrs. There were 4,486 (23.3%) fatal‐case outcomes. PE occurred least frequently in spring (n=4,442 or 23.1%) and most frequent in winter (n=5,236 or 27.2%, goodness of fit χ²=75.75, p<0.001). Similar results were obtained for subgroups formed by gender, age, fatal/non‐fatal outcome, presence/absence of major underlying co‐morbid conditions, and specific risk factors. Inferential chronobiological analysis identified a significant annual pattern in PE, with the peak between November and December for the total sample of cases (p<0.001), males (p<0.001), females (p=0.002), fatal and non‐fatal cases (p<0.001 for both), and subgroups formed by age (<65 yrs, p=0.012; 65–74 yrs, p<0.001; ≥75 yrs, p=0.012). This pattern was independent of the presence/absence of hypertension (p=0.003 and p<0.001, respectively), pulmonary disease (p<0.001 and p<0.001, respectively), stroke (p<0.001 and p=0.004, respectively), neoplasms (p=0.005 and p=0.001, respectively), heart failure (p=0.022 and p<0.001, respectively), and deep vein thrombosis (p=0.002 and p<0.001, respectively). However, only a non‐statistically significant trend was found for subgroups formed by cases of diabetes mellitus, infections, renal failure, and trauma.     

Matrix metalloproteinase-9 and plasminogen activator inhibitor-1 are associated with right ventricular structure and function: The MESA-RV Study

Elevated resistance and reduced compliance of the pulmonary vasculature increase right ventricular (RV) afterload. Local and systemic inflammation and haemostatic abnormalities are prominent in pulmonary vascular diseases. We hypothesized that plasma biomarker levels indicating greater inflammation and coagulability associated with pulmonary vascular disease would be associated with RV structure and function measured by cardiac magnetic resonance imaging (MRI). The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI among participants aged 45–84 years without clinical cardiovascular disease. We assessed the associations of RV mass, RV end-diastolic volume (RVEDV), RV stroke volume (RVSV) and RV ejection fraction (RVEF) with plasma measures of inflammation (matrix metalloproteinase (MMP)-3 and -9, intercellular adhesion molecule (ICAM)-1, tumour necrosis factor receptor (TNF-R1), and E-selectin) and thrombosis (plasminogen activator inhibitor (PAI)-1, tissue factor, tissue factor pathway inhibitor and CD40 ligand).The study sample included 731 subjects. Higher MMP-9 levels were associated with lower RV mass before and after adjustment for left ventricular (LV) mass (p?=?0.008 and p?=?0.044, respectively). Higher levels of MMP-9 and PAI-1 were also associated with smaller RVEDV (p<0.05). Higher PAI-1 levels were associated with lower RVEF even after adjustment for LV ejection fraction (p?=?0.017). In conclusion, MMP-9 and PAI-1 are associated with changes in RV structure and function which could be potentially related to a subclinical increase in pulmonary vascular resistance.     

128排CT对股骨头置换术后下肢深静脉血栓形成的诊断价值分析

摘要 目的：探讨与分析128排电子计算机断层扫描(Computed Tomography,CT)对股骨头置换术后下肢深静脉血栓形成的诊断价值。方法：2015年1月到2020年7月选择在本院诊治的股骨头置换术后疑似下肢静脉血栓形成患者78例作为研究对象,所有患者都给予128排CT检查,记录影像学特征并判断诊断价值,分析下肢深静脉血栓形成的影响因素。结果：在78例患者中,128排CT判断图像优69例,良9例,优良率为100.0 %。静脉造影判定为术后发生下肢深静脉血栓形成11例(DVT组),发生率为14.1 %,检出病变血管45支。二分类多因素Logistic回归分析显示术中出血量、手术时间、使用激素、年龄是导致股骨头置换术后下肢深静脉血栓形成的重要因素(P<0.05)。DVT组的血容量(cerebral blood volume,BV)与达峰时间(time to peak,TTP)值高于非DVT组(P<0.05),血流量(blood flow, BF)与平均通过时间(mean transit time,MTT)值低于非DVT组(P<0.05)。DVT组的血管狭窄评分低于非DVT组(P<0.05)。128排CT对股骨头置换术后下肢深静脉血栓形成的诊断敏感性与特异性为100.0 %和97.0 %。结论：术中出血量、手术时间、使用激素、年龄是导致股骨头置换术后下肢深静脉血栓形成的重要因素,128排CT能有效检出下肢深静脉血栓形成情况,具有方便、快捷、无创的特点,可为临床诊治提供可靠依据。     

Prevalence of the fibrinogen β‐chain,angiotensin‐converting enzyme and plasminogen activator inhibitor‐1 polymorphisms in Costa Rican young adults with thrombotic disease

Thrombotic disease is a multifactorial condition that involves both classical and genetic risk factors. We studied the association between the classical risk factors of hypertension and smoking, and polymorphisms on the genes of the angiotensin‐converting enzyme (ACE), the β‐chain of fibrinogen (FG), and the plasminogen activator inhibitor‐1 (PAI‐1) in patients with venous and arterial thrombosis. The present investigation is a retrospective case–control study. A total of 340 participants were analyzed, including 162 patients and 178 healthy controls. Hypertension and smoking showed a significant association with thrombotic disease (p < 0.05) but FG level was found significant risk factor only for the venous thrombosis (VT) group (p < 0.04). Significant differences between thrombotic groups were found for the studied polymorphisms of PAI‐1 (p < 0.0014), but for both FG β‐chain gene polymorphisms, none of the molecular analyses showed a positive sample for any mutating allele (p > 0.05). For the ACE polymorphism, the I allele present a protective effect in the general thrombotic group. This is one of the first reports in a Latin‐American population dealing with these molecular markers and thrombotic diseases. Copyright © 2010 John Wiley & Sons, Ltd.