Circulating tissue factor positive microparticles in patients with acute recurrent deep venous thrombosis

Introduction

Circulating tissue factor positive microparticles (MPTF) were reported in a wide range of diseases with thrombotic tendency. Though D-dimer assay had a high negative predictive value for deep venous thrombosis (DVT) recurrence, there are currently no reliable positive predictors for recurrent DVT. We therefore quantified MPTF in patients with acute recurrent DVT to determine whether MPTF levels could be used to predict recurrent DVT.

Materials and Methods

Microparticles (MPs) were isolated from plasma of initial DVT patients (n = 25), recurrent DVT patients (n = 25) and sex- and age-matched healthy individuals (n = 25), stained with annexin V, cell-specific monoclonal antibodies (MoAbs) and a MoAb directed against tissue factor (TF), and analyzed by flow cytometry. We also determined the plasma procoagulant activity with a Human TF Chromogenic Activity Assay Kit.

Results

We found total MPTF to be elevated in recurrent DVT patients versus normal individuals (P = 0.001). The number of monocyte-derived MPTF in both initial and recurrent DVT was higher than in normal individuals (P < 0.01, respectively). The platelet and endothelial cell derived MPTF in recurrent DVT were significantly increased relative to other MPTF (P < 0.05), although there was no difference between initial DVT patients and normal individuals. We demonstrated elevated procoagulant activity of platelet-free plasma in DVT patients relative to normal individuals, and a positive correlation with MPTF.

Conclusions

The elevated MPTF could be a potentially predictor for DVT recurrence. Further studies are needed to validate its sensitivity and specificity.     

冠状动脉性心脏病患者外周血中CD144+/Annexin V+ 内皮微颗粒水平的变化

目的测定冠状动脉性心脏病患者外周血内皮微颗粒的水平,研究其与各种临床指标的相关性,探讨CD144+/Annexin V+内皮微颗粒与冠状动脉性心脏病患者发生急性缺血事件的关系。方法经冠状动脉造影确诊的冠状动脉性心脏病患者81例,根据临床症状、心电图及超敏肌钙蛋白结果将患者分为急性冠状动脉综合征组(A组,51例)和稳定型心绞痛组(B组,30例)。采用流式细胞术检测两组患者外周血中CD144+/Annexin V+的内皮微颗粒的水平,评估CD144+/Annexin V+内皮微颗粒与年龄、心率、血压、血脂、血糖、炎性指标、心肌标志物等各临床指标之间的相关性。结果与B组相比,A组的外周血CD144+/AnnexinV+内皮微颗粒的水平显著升高(P<0.01)。CD144+/Annexin V+内皮微颗粒的水平与脂蛋白a(r=0.886)、超敏C反应蛋白(r=0.404)、肌酸激酶同工酶(r=0.471)和超敏肌钙蛋白(r=0.240)均呈正相关(P值分别<0.01、0.05),与年龄、心率、收缩压、舒张压、脉压差、空腹血糖、餐后2h血糖、糖化血红蛋白、总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇均不相关(P值均>0.05)。结论外周血CD144+/AnnexinV+内皮微颗粒的水平与脂蛋白a、超敏C反应蛋白、肌酸激酶同工酶、超敏肌钙蛋白有关,对于评价冠状动脉性心脏病高危状态具有较好的价值。     

Improvement in the cardiovascular profile of patients with morbid obesity following bariatric surgery: Effect on hypercoagulability

Obesity is an inflammatory state related to vascular endothelium dysfunction. It generates a biological situation of hypercoagulability increasing the risk of thrombosis. This prothrombotic condition could be improved by bariatric surgery.The main objective was to analyze the impact of bariatric surgery on cardiovascular risk factors (CVRF) associated with changes in thrombin generation and procoagulant activity of microparticles (MP).We present a prospective longitudinal study including consecutive patients candidate for bariatric surgery. We performed 3 sequential clinical visits: at inclusion, before surgery after completing the modified fasting phase, and 6 months after surgery. We analyzed CVRF, thrombin generation, and MP activity. The data analysis was performed using a logistic regression model to determine changes over time of hemostatic parameters and body mass index (BMI). McNemar test for binary variables was used to analyze the CVRF.We included 94 patients (66 women), with an average age of 45.7 ± 10.1 years. The mean BMI reduction at the end of the follow-up was 15.5 ± 4.2 kg/m². We detected a statistically significant improvement in CVRF: hypertension, diabetes mellitus, dyslipidemia, and obstructive sleep apnea, as well as a significant reduction in thrombin generation capacity and procoagulant MP activity.Massive weight loss induced by bariatric surgery improves the cardiovascular profile, associated with a reduction in the hypercoagulable status.     

口服胰岛素微粒剂降血糖有效性及大鼠胃肠道有效吸收部位的研究

分别以葡萄糖氧化酶法、放射免疫分析法对服用微粒剂后的四氧嘧啶致糖尿病小鼠与狗的血糖、血清胰岛素进行测定 ,验证确有外源性胰岛素进入动物体内 ,在给药后 1h动物血清胰岛素增至最高 ,约 2h动物血糖降至最低 ,且作用强度、时间与血清胰岛素变化相对应。给药剂量在 4 0～35 0u/kg范围 ,存在量效关系 :Y(% ) =13 2 1- 1 70 7X(u/kg) ,r =0 9788。给小鼠腹腔注射葡萄糖 (2 g/kg)可见 ,微粒剂 (17u/kg)能对抗并减缓因注射外源还原性单糖引起的动物血糖升高 ,0 5h可抵抗百分率达 86 % (P <0 0 0 5 )。经四氧嘧啶糖尿病大鼠胃肠道不同部位给药发现 :给药部位不同 ,微粒剂降血糖程度有显著差别 ,其中经回肠部位给药效果最好 ,降血糖百分率达 5 6 %(P <0 0 1)。     

胰岛素微粒剂的制备、含量、包裹率与生物活性稳定性

采用生物效价与放射免疫分析两种方法对微粒剂胰岛素含量进行测定．通过胰岛素放射免疫活性分析测定了胰岛素包裹率．以胰岛素生物效价为指标,采用恒温加速实验考察了微粒剂的生物活性稳定性,结果表明：微粒剂胰岛素含量分别为０－５１ｕ／ｍｇ 与０－５５ＩＵ／ｍｇ;包裹率在９０ ％以上;室温放置１ 年,未见生物活性明显改变;２５ ℃生物活性有效期为１２－５ 月．     

Orodispersible Films with Rupatadine Fumarate Enclosed in Ethylcellulose Microparticles as Drug Delivery Platform with Taste-Masking Effect

Orally disintegrating (orodispersible) films provide a versatile tool for drug administration, especially in the pediatric and geriatric population, since they reduce the risk of choking and do not necessitate drinking water during application. By considering their direct contact with the taste buds, palatability is an influential aspect related to patient compliance. The microparticles based on taste-masking polymers containing drugs enclosed inside effectively mask the unpleasant taste of medicines. Ethylcellulose is a hydrophobic polymer widely used as a taste-masking material. Rupatadine fumarate, a second-generation antihistamine drug, is characterised by an intense bitter taste; therefore, it is crucial to achieve a tolerable taste whilst developing orodispersible formulations with its content. The objective of this study was to develop orally disintegrating films with rupatadine fumarate in the form of ethylcellulose-based microparticles obtained from aqueous dispersions of ethylcellulose—Surelease^® or Aquacoat^® ECD. It was a technological challenge to achieve homogenous drug content per dosage unit and sufficient mechanical properties for film operating due to the necessity to suspend the microparticles in the casting solution. Although the process of obtaining films consisted of several steps (mixing, pouring, drying), the particles were homogeneously dispersed, and each film of the desired size contained the proper dose of the drug. The taste-masking effect was also maintained. This parameter was confirmed by three independent methods: in vivo by healthy volunteers, an electronic tongue and a dissolution test. The applied taste-evaluation techniques showed that the films containing Aquacoat^® ECD microparticles have the highest degree of bitter taste reduction, which confirms the results obtained in our previous studies.     

Synthesis of Crosslinked Microparticles Based on Glycidyl Methacrylate and N-Vinylimidazole

In this study, suspension polymerization technique is used to obtain 3D porous networks based on two monofunctional monomers (glycidyl methacrylate and N-vinylimidazole) and one of the following difunctional monomers known as crosslinking agents: mono-, di-, and triethylene glycol dimethacrylate or divinylbenzene. The influence of various operational parameters like: monomer molar ratio, amount and type of crosslinkers, composition of stabilization system, stirring speed, amount of porogenic agent on the reaction yield, surface morphologies, particle size distribution, and porous characteristics are investigated in order to find the optimal conditions for the synthesis of microparticles possessing the desired properties for further chemical modification. Crosslinked porous microparticles are structurally characterized by Fourier transform inrared  (FTIR) spectroscopy, X-ray photoelectron spectroscopy, and elemental analysis by determination of nitrogen and epoxy groups. The microparticle morphologies as a function of investigated parameters are revealed by scanning electron microscopy, whereas the porous structure is highlighted by mercury porosimetry and dynamic water vapor sorption methods. All the crosslinked networks exhibit porous structures with different surface morphologies and specific surface area values (1.15–48.32 m² g⁻¹) depending on the operational parameters. These microparticles can be considered precursors for the preparation of various functional polymeric materials.     

血小板微粒对大动脉粥样硬化型脑梗死近期预后的预测价值分析

目的 探讨血小板微粒与大动脉粥样硬化型脑梗死患者近期预后的关系及其预测价值。方法 选取2015年7月—2020年11月在青岛市中医医院诊断为大动脉粥样硬化型脑梗死患者152例，均经治疗后好转出院。根据患者出院后30 d的预后情况，分为预后不良组（37例）和预后良好组（115例）。比较两组患者的临床资料、血小板微粒、NIHSS及mRS评分；采用多因素Logistic回归分析预后的影响因素；采用受试者工作特征（ROC）曲线评估血小板微粒对预后的预测效能；绘制Kaplan-Meier曲线，分析血小板微粒与生存时间的关系。结果 预后不良组患者的血小板微粒水平、NIHSS评分及mRS评分高于预后良好组；多因素Logistic回归分析结果显示，血小板微粒[■=2.204(95%CI:1.547,3.128)]、NIHSS评分[■=1.784(95%CI:1.295,2.436)]及mRS评分[■=1.133(95%CI:1.057,1.206)]与预后不良有关（P <0.05）;ROC曲线分析结果显示，血小板微粒预测预后不良的曲线下面积为0.854(95%CI:0.792,0.906)，敏感...     

酒精性股骨头缺血性坏死发病机理的研究进展

随着人均酒精消费量的上升,酒精性股骨头缺血性坏死的临床病例也明显的增多。通过对成人酒 精性股骨头坏死的研究,认为其发病机制与脂质代谢异常、血管内异常、氧自由基代谢异常、基因多态性、骨质疏 松、细胞膜微粒及内皮素、一氧化氮代谢等异常有关。     

不同形式脂肪微粒在创面修复中的应用进展

现阶段烧伤、压疮、放射性溃疡等为创面修复的难题，引流、植皮以及皮瓣修复等方法虽有一 定治疗效果，但无法满足患者外观要求。脂肪微粒移植术通过提取患者自身皮下脂肪，经过抽吸净化后获 取符合要求的脂肪颗粒组织，将其注入到机体所需部位，可到达良好的整形、美容效果，但不同形式的脂 肪微粒移植术的应用效果和适用范围存在差异。本文主要分析不同形式脂肪微粒在创面修复中的应用进 展，以期为提高皮肤创面修复提供更多选择。