LOW MOLECULAR WEIGHT HEPARIN DECREASES THE ALBUMINURIA AND RENAL PATHOLOGICAL CHANGES IN DIABETIC NEPHROPATHY RATS

Objective To investigate the renoprotection effect of low molecular weight heparin（LMWH）in diabetic rats.Methods Diabetic rats were induced by injection of steptozotocin（STZ）.Rats were randomly divided into three groups：control group,diabetic model group,and LMWH treatment group.The levels of total cholesterol（TC）,triglyceride（TG）,prothrombin time（PT）,kaolin partial thromboplastin time（KPTT）,24-hour urinary albumin excretion rate（UAER）,and serum soluble P-selectin were determined after 8 weeks.Glomerular morphology was observed by light microscopy.Results The levels of TG,UAER,and P-selectin in LWMH treatment group were lower than those in model group（all P〈0.01）.The levels of PT and KPTT in LWMH treatment group were shorter than those in model group.And LWMH improved the histological changes of diabetic rats.Conclusion LMWH has some renal protective effects in diabetic rats,partly through down-regulating the expression of P-selectin.     

Effect of low molecular weight heparin on pancreatic micro- circulation in severe acute pancreatitis in a rodent model

Background Alleviation of microcirculation disorders in severe acute pancreatitis (SAP) can improve survival rates, and low molecular weight heparin (LMWH) is well known to have potent ameliorative effect on microcirculation disorders caused by anti-coagulant activity. The aim of this study was to investigate the effects of LMWH on pancreatic microcirculation in SAP in rats. Methods SD rats were randomly divided into 3 groups: sham operation (S) group, SAP group, and LMWH treatment (LT) group. The concentrations of serum amylase, tumor necrosis factor-alpha (TNF-α), endothelin-1 (ET-1), pancreatic ultrastructure were examined at 24 hours after the models were set up in each group. Results Compared with S group, the concentration of serum amylase, ET-1, and TNF-α in SAP group were significantly increased (P<0.001); After LMWH treatment, the concentration of serum amylase, ET-1, TNF-α were decreased significantly compared with SAP group (P<0.001, 0.01, 0.001, respectively). On electron microscopy, the microthrombosis in LT group was significantly less than that in SAP group. The 3-day survival rate in SAP group (25.0%) was significantly lower than that in S group (100.0%, P<0.05) and in LT group (87.5%, P<0.05).Conclusions The disorder of pancreatic microcirculation may be involved in the inflammatory response of rats with SAP. LMWH can effectively improve the survival rate of SAP, and alleviate the severity of microcirculation disorders through its antithrombin effects and down-regulate the levels of serum ET-1 and TNF-α.     

Evaluation on the efficacy and safety of domestic bivalirudin during percutaneous coronary intervention

Background Bivalirudin was widely used as an anticoagulant during coronary interventional procedure in western countries.However,it was not available in China before this clinical trial was designed.This randomized,single-blind and multicenter clinical trial aimed to evaluate the efficacy and the safety of domestic bivalirudin during percutaneous coronary intervention （PCI）.Methods A randomized,single-blind,multicenter trial was designed.Elective PCI candidates in five centers were randomized into a bivalirudin group and a heparin group,which were treated with domestic bivalirudin and non-fractional heparin during the PCI procedure.The efficacy was evaluated by comparing the activated coagulation time （ACT）,the procedural success rate （residual stenosis ＜20％ in target lesions without any coronary artery related adverse events within 24 hours after PCI）,and the survival rate without major adverse cardiac events at 30 days after PCI between the two groups.Safety was evaluated by the major/minor bleeding rate.Results A total of 218 elective PCI patients were randomized into a bivalirudin group （n=110） and heparin group （n=108）.Except for two patients needing additional dosing in the heparin group,the ACT values of all other patients in both groups were longer than 225 seconds at 5 minutes after the first intravenous bolus.Procedural success rates were respectively 100.0％ and 98.2％ in the bivalirudin group and heparin group （P＞0.05）.Survival rates without major adverse cardiac events at 30 days after PCI were 100.0％ in the bivalirudin group and 98.2％ in the heparin group （P＞0.05）.Mild bleeding rates were 0.9％ and 6.9％ （P＜0.05） at 24 hours,and 1.9％ and 8.8％ （P＜0.05） at 30 days after PCI in the bivalirudin group and heparin group respectively.There was one severe gastrointestinal bleeding case in the heparin group.Conclusions Domestic bivalirudin is an effective and safe anticoagulant during elective PCI procedures.The efficacy is not inferior to heparin,but the safety is superior to heparin.     

Corneal permeability assay of topical eye drop solutions in rabbits by MRI

This study examined the corneal permeability of topical eye drop solutions added with various corneal penetrating accelerators and gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) by nuclear magnetic resonance imaging (MRI).Twenty-four New Zealand rabbits were randomly divided into 3 groups according to the random digits table:Gd-DTPA group,in which the rabbits received 23.45% Gd-DTPA;hyaluronic acid group,in which 23.45% Gd-DTPA plus 0.2% hyaluronic acid was administered;azone group,in which 23.45% Gd-DTPA with 0.2% azone was given.Fifty microliters of the eye drops was instilled into the conjunctive sac every 5 min,for a total of 6 applications in each group.Contrast medium signals in the cornea,anterior chamber,posterior chamber,and vitreous body were scanned successively by MRI.The morphology and cell density of the corneal endothelium were examined before and 24 h after the treatment.The results showed that the residence time of Gd-DTPA in the conjunctival sac in the hyaluronic acid and azone groups was longer than that in the Gd-DTPA group.The signals in the anterior chamber of the Gd-DTPA and hyaluronic acid groups were increased slightly,and those in the azone group strengthened sharply.The signal intensity continuously rose over 80 min before reaching plateau.The strengthening rate of signals in the anterior chamber was 19.63% in the Gd-DTPA group,53.42% in the sodium hyaluronate group,and 226.94% in the azone group.No signal was detected in the posterior chamber or vitreous body in all the 3 groups.Corneal morphology and cell density did not show any significant changes after the treatment in all the 3 groups.It was concluded that azone can significantly improve the corneal permeability of drugs that are similar to Gd-DTPA in molecular weight and molecular size,and MRI is a noninvasive technique that can dynamically detect eye drop metabolism in real time.     

Experimental Study on the Enhancement of Rat Skull Defects Repair by Induced Osteogenesis

The repairing capacities of bone matrix gelatin(BMG),decalcified bonematrix(DBM)and deep frozen bone(DFB)were tested in experimental defects onskulls of rats.The healing of defects were judged by roentgenographic,histological and atomic absorption spectrophotometric methods.The healing ofdefects was most effective with BMG(P<0.01),and DMB came next while thecapability of bone induction was very weak in DFB.In the BMG and DBMgroups,skull defects were completely healed in 12 weeks after the operation,but inthe DFB group healing was incomplete.The control group failed to healspontaneously.The results suggest that during the process of resorption of BMGand DBM,bone morphogenetic protein(BMP)was released by diffusion,whichinduced mesenchymal cells originating from the dura mater to differentiate intochondrocytes and osteobIasts,resulting in formation of new bone.The inducedosteogenesis is considered to be a complex process regulated not only by BMP butalso by various systemic and local growth factors.     

In vitro effect of biologically active coating on endothelialisation of Nitinol coils designed for the closure of intracardiac shunt

To evaluate in vitro the effect of biologically active coating on endothelialisation of Nitinol coils designed for the dosure of intracardiac shunt. Methods: Covalently binding procedure was performed with chemical vapor deposition (CVD).Heparin(200 IU/ml),r-hirudin(21 nmol/ml),or fibronectin(15 μg/ml),respectively, were bound to the basic coating(poly( amino-p-xyly-lene-co-p-xylylen) ). In vitro tests were performed on five different coating groups(n=2 each):uncoated Nitinol, basic coating,heparin-,r-hirudin-,and fibronectin-coating. Human umbilical vein endothelial cells(HUVECs) were cultured in the presence of tested coils for 48 and 72 h. Adhesion of HUVECs were evaluated with light microscopy,and with confocal laser scanning microscopy after double-staining of vinculin, phalloidin, Ki67 and fibronectin. Results: After 48 and 72 h of incubation, except HUVECs around the basic coating showing ab-normal morphology, HUVECs were able to grow next to all kinds of coils. By CLSM adhering cells were typically confined to maximal three secondary coil windings. HUVECs adhered best to the fibronectin coated coils, followed by the uncoated Nitinol. HUVECs barely adhered to the basic coating. The adhesion to heparin coating or r-hirudin coating was observed with various cell densities. Heparin coating seemed to support cell adhesion better than r-hirudin coating did. The HUVECs assembled fibronectin matrix on the fibronectin coating and Nitinol coil. Vinculin was expressed on both fibronectin coating and uncoated Nitinol as well, mostly diffused, but occasionally also in focal contacts. Ki67 expression was mainly noticed on the uncoated Nifinol coil and fibronectin coated coil, only occasionally on other materials. The densities and morphology of HUVECs, adhered to the correspohding well surfaces, were similar for all wells. The only exception was the well with the basic coating coil after three days of incubation. In this case, the cell density was diminished,and the cells became more elongated. The cells grown on the well surfaces exhibited a more profound matrix assembly and more pronounced focal adhesions than the cells adhered to the coil surfaces did. Condusion: Except for basic coating,biologically active substance coated or uncoated coils show no acute cytotoxicity on HUVECs. Due to better cell proliferation,cell matrix assembling,and focal adhesion,only fibronectin coating improves the endothelialisation of Nitinol coils。     

Aspirin combined with mechanical measures to prevent venous thromboembolism after total knee arthroplasty: a randomized controlled trial

Background Venous thromboembolism （VTE） is an important complication after major orthopedic surgery.Pharmaceutical methods represent the main strategy of VTE prevention.The use of aspirin in VTE prevention is still controversial worldwide,especially in China.The purpose of this study was to evaluate the role of aspirin combined with mechanical measures in the prevention of VTE after total knee arthroplasty （TKA）.Methods Between January 2012 and May 2013 and in accordance with the inclusion criteria,120 patients undergoing TKA were randomly allocated to two groups.To prevent VTE,patients in group A received aspirin combined with mechanical measures postoperatively,while patients in group B received low-molecular-weight heparin （LMWH） sodium and rivaroxaban sequentially in combination with mechanical measures postoperatively.All surgeries were performed by one surgeon using a posterior-stabilized cemented prosthesis.The two groups were followed up and compared for the incidence of deep vein thrombosis （DVT） by duplex ultrasound scan and clinical VTE events.The adverse events,the blood loss index,and the cost of VTE prevention were also compared.Results DVT was detected in 10 of 60 patients in group A （16.7％,95％ CI：7.3％-26.1％） compared with 11 of 60 in group B （18.3％,95％ CI：8.5％-27.8％） （P=0.500）.There is no statistical evidence supporting the inferior effect of aspirin in preventing DVT as compared with the other medications.There were no cases of symptomatic VTE or death during the follow-up period.Area of ecchymosis was lower in group A than in group B,and the differences were statistically significant.Patients in group A had the lower blood loss index as compared with patients in group B.No transfusion cases were found in both groups.The differences were statistically significant.The cost of VTE prevention analysis indicated a cost reduction using aspirin in group A compared with using LMWH and rivaroxaban in group B.Conclusion Aspirin combined with mechanical measu     

A randomized comparative study of using enoxaparin instead of unfractionated heparin in the intervention treatment of coronary heart disease

Several international multicenter studies have demonstrated that low molecular weight heparin (LMWH) was more effective than unfractionated heparin (UFH) in treating acute coronary syndrome (ACS).1-4 However, it remains uncertain whether LMWH can be used in patients undergoing percutaneous coronary intervention (PCI) instead of UFH. In an expert consensus on the use of LMWH in the catheter laboratory published in 2002,5 there were two recommendations which limited the use of LMWH in…     

Proto-oncogenes expression in the process of asthma airway remodeling

Objective: To observe the expression of proto-oncogenes in the process of airway remodeling in asthma. Methods: Guinea pig was used as an asthma model challenged by ovoglobulin. Dot-blot, Northern-blot molecular hybridization and immunohistochemistry techniques were used to detect the expression of c-fos, c-myc, c-jun and c-sis. Results: Expression of c-fos and c-myc mRNA could not be detected or detected at very low level in the control group. There were greatly increased expression of c-fos and c-myc mRNA after guinea pigs were challenged by ovoglobulin. Thirty minutes after the challenge, the expression of c-fos and c-myc mRNA reached to the peak and returned to normal level 4 h after the challenge. Immunohistochemistry studies showed that Fos, Myc, Jun and Sis expressed at low level in control group and increased after ovoglobulin stimulation. Immunohistochemically positive cells laid in the plasma of airway epithelium, in cell nucleus of bronchial epithelium and in the inflammatory cells. Pathologic     

封堵器透明质酸钠肝素微囊化涂层的研制

目的本研究将封堵器进行肝素涂层,通过局部肝素的缓慢释放,达到抗血栓目的,避免先心病介入治疗后需要长期服用抗血栓药物来避免血栓形成的现状。方法首先将肝素降解成低分子肝素,借助油包水(w/o)乳化交联技术制备了新型肝素微胶囊,并对其性能进行了一定的研究。同时,将制备的肝素明胶粒子采用透明质酸钠涂层方法进行镍钛合金封堵器的涂层。结果各种影响因素中明胶浓度对肝素微胶囊制备影响最大,明胶浓度为1%时肝素微胶囊粒径多在100 um以内,最佳制备工艺所得LMWH-GMS的包封率约为80%;封堵器采用透明质酸钠涂层时涂层均匀、不易脱落。结论本研究成功地将肝素降解成低分子肝素,通过微胶囊化技术可将低分子肝素制成粒径纳米级微胶囊并保持抗血栓特性;应用透明质酸钠涂层方法可以成功地对镍钛合金封堵器进行涂层。     

经导管应用新型无膜双腰封堵器封堵犬单侧肾动脉

目的 在大动物中观察新型无膜双腰封堵器应用的安全性及有效性.方法 选取健康实验犬12只,应用新型无膜双腰封堵器进行单侧肾动脉封堵,封堵后即刻行肾动脉造影评估封堵效果,并于术后1、3及6个月复查肾动脉造影.复查造影结束后处死实验犬,观察肾脏大体标本并行肾脏病理检查,并观察封堵器表面内皮化情况.结果 12只实验犬均成功实施单侧肾动脉封堵,其中1只因麻醉药物过量死亡,其余11只存活良好.6只实验犬在植入封堵器后即刻完全封堵,全部实验犬均在植入封堵器后12 min内完全封堵肾动脉血流.封堵器释放后,封堵器位置均固定良好,未见明显封堵器移位.所有实验犬复查肾动脉造影均显示封堵器位置固定良好,无残余分流.大体观察发现封堵侧肾脏较对侧肾脏明显缩小,肾脏表面凹凸不平,质略硬.内皮细胞在术后1个月即开始覆盖封堵器表面,3个月时内皮细胞完全覆盖.结论 新型无膜双腰封堵器具有良好的安全性、组织相容性及有效性,由于其优异的通过性,在小外径鞘管内即可完成封堵器输送.     

New Nano-Film Single-Rivet Patent Ductus Arteriosus Occluders: A Prospective,Randomized and Double-blind Study

Nitinol alloy occluders are widely used in the transcatheter intervention treatment of congenital heart diseases like patent ductus arteriosus (PDA). However, nitinol alloy contains high levels of nickel, which can lead to toxic effects in the immune and hematopoietic systems if released in sufficient quantities. A new type of single-rivet occluder coated with nano-film has been developed to limit the release of nickel. In total, 23 patients were recruited and randomly assigned to the experimental group (n=12) with the new nano-film single-rivet occluders or the control group (n=11) with the traditional occluders. One case in the control group was lost to follow-up. The remaining 22 cases were followed up at 24 h, 7 days, 1 month, 3 months, and 6 months after the procedure. There were no statistically significant differences in routine blood test, alanine aminotransferase, creatinine, and troponin between the experimental and control groups. Serum nickel concentration in both two groups increased at 24 h after the procedure, peaked at 1 month, and returned to preoperative levels at 6 months. Serum nickel levels in the experimental group were significantly lower than in the control group at 24 h, 7 days, 1 month, and 3 months after the procedure. These data suggested that the nano-film coating effectively prevented nickel release from the new occluders, and therefore has a preferable safety profile.     

低分子肝素治疗急性脑梗塞33例临床观察

目的　探讨低分子肝素 (low molecularweightheparin ,LMWH ,立迈青 )治疗急性脑梗塞的临床疗效。方法　将 6 6例急性脑梗塞患者随机分为A、B两组 ,每组各 33例 ,A组应用LMWH5 0 0U ,腹壁皮下注射 ,每日 2次 ,连续 10天。B组应用低分子右旋糖酐 5 0 0ml+川芎嗪 16 0mg ,静脉滴注 ,每日 1次 ,连续 10天。结果　LMWH可改变血液流变学 ,但不减少血小板数量及纤维蛋白原量、凝血酶原时间、出血时间。结论　低分子肝素治疗急性脑梗塞安全 ,疗效较好     

低分子肝素治疗脑梗死的临床疗效观察

目的：探讨低分子肝素治疗脑梗死的临床疗效。方法：选取脑梗死患者138例，随机分为治疗组68例，对照组70例。对照组予丹参10ml及胞磷胆碱1．0g分别加入0．9%NS 250ml静脉点滴，1次／d为基础治疗，治疗组在对照组的基础治疗上加用低分子肝素4100IU脐旁皮下注射，2次／d，治疗10d。结果：低分子肝素治疗组总有效率86．76％，对照组总有效率71．43％，治疗组疗效明显优于对照组（P＜0．05）。结论：低分子肝素治疗急性脑梗死安全有效。     

经食管超声心动图在婴幼儿多发性房间隔缺损经胸微创封堵术中的应用

目的 探讨经食管超声心动图在婴幼儿多发性房间隔缺损（ASD）经胸微创封堵术中的应用价值。方法 18例多发性ASD患儿,经右侧胸骨旁微创小切口显露右心房。在术中食管超声心动图（TEE）指引下,测量ASD的大小及数目、孔间距,并据此选择合适类型的房间隔缺损封堵器。TEE引导封堵器的套管经房间隔缺损进入左房并对多发性ASD进行封堵,术后即刻评价封堵器治疗多发性房间隔缺损的效果。结果 18例患者均采用1个封堵器封堵多发性ASD成功。术后即刻TEE检查所有患儿封堵器位置良好,封堵器无变形、移位和脱落,多发性ASD无残余分流,心脏瓣膜功能不受影响。结论 经胸微创封堵术治疗婴幼儿多发性ASD是安全、有效的技术,TEE对病例和封堵器的选择及术中引导和监测、术后随访均具有重要的临床意义。     

低分子肝素纳米脂质体的制备及大鼠口服吸收

目的：制备低分子肝素纳米脂质体制剂，并进行大鼠口服吸收的研究。方法：用超声波分散法制备低分子肝素纳米脂质体，以正交实验设计确定最佳制备工艺；电镜观察其形态及粒径分布，以大鼠用药前后血液凝固时间的变化研究其口服吸收的促进作用。结果：低分子肝素纳米脂质体在民镜下为圆形或椭圆形，平均粒径为89．6mm，包封率为36．1％，大鼠用药后血液凝固时间显著延长。结论：纳米脂质体对低分子肝素大鼠口服吸收有良好的促进作用。     

低分子肝素对进展型脑梗死的临床疗效观察

目的观察低分子肝素治疗进展型脑梗死的临床疗效。方法将70名患者随机分为两组。34例对照组,采用常规治疗,即应用血栓通针5ml,每天1次静脉注射,36例治疗组在对照组治疗的基础上加用低分子肝素钙5000U皮下注射,每天1次,10d为1个疗程,观察两组患者治疗前后神经功能缺损评分、日常生活能力的评定变化。结果治疗组患者治疗后3周的基本治愈率、显著进步率高于对照组,治疗组治疗3周后的日常生活能力的评分明显高于对照组。结论低分子肝素治疗进展型脑梗死安全有效。     

低分子肝素对大鼠脑局灶性缺血再灌注后Bcl-2,Bax表达的影响及保护作用

目的:观察低分子肝素对大鼠脑缺血再灌注后不同时间点Bcl-2,Bax表达的影响及保护作用. 方法:①选用雄性SD大鼠54只,体质量280～330 g. 应用随机数字表法将大鼠分为3组:假手术组、缺血再灌注组和低分子肝素组,每组18只. ②应用免疫组化方法测定海马CA1区神经元细胞凋亡基因Bcl-2,Bax表达情况. ③采用两样本均数的t检验对两组间数据进行分析. 结果:大鼠54只均进入结果分析,缺血再灌注组大鼠脑缺血再灌注6,12,24 h时Bcl-2蛋白在神经元内表达的阳性细胞数较低分子肝素组同一时间点明显减少,两组比较具有显著的统计学意义(P＜0.05). 缺血再灌注组大鼠脑缺血再灌注6,12,24 h时Bax蛋白表达的阳性细胞数较低分子肝素组同一时间点明显增加,两组比较具有显著的统计学意义(P＜0.05). 结论:脑缺血再灌注损伤随再灌注时间延长而加重,低分子肝素可能通过减少Bax蛋白的表达,上调Bcl-2蛋白表达,从而减轻神经元的损伤及凋亡,起到脑保护作用.     

低分子肝素钠联合银杏达莫治疗进展性缺血性脑卒中疗效观察

目的：观察低分子肝素联合银杏达莫治疗进展性缺血性脑卒中的疗效。方法：选择135例发病在12～48h,病情呈进行性加重的进展性缺血性脑卒中患者,随机分为3组,分别接受低分子肝素治疗、银杏达莫治疗、低分子肝素和银杏达莫联合治疗。1个疗程后作疗效判定,并监测治疗前后血液流变学的变化。结果：1个疗程后低分子肝素组总有效率为80.0%、联合用药组总有效率为88.9%,明显高于银杏达莫组的71.1%,而且治疗前后血流变学的变化亦有显著性的差异,特别以联合用药组的总有效率最高和血流变学变化最明显,同时未发现出血倾向等不良反应。结论：低分子肝素能有效地治疗进展性缺血性脑卒中,与银杏达莫联合使用具有协同作用,临床疗效确切、安全。