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African trypanosomes are the causative agents of sleeping sickness in humans and of Nagana in cattle. The infectivity of African trypanosome species for humans appears to be defined by their susceptibility to two lytic factors in human serum; trypanosome lytic factor (TLF)1, a subclass of human high density lipoprotein (HDL) and TLF2, a high molecular weight protein complex. Available evidence indicates that following receptor mediated uptake, TLF is targeted to the lysosome where the low pH triggers a TLF-dependant peroxidase activity resulting in the formation of reactive oxygen radicals with consequent lipid peroxidation and destruction of the lysosomal membrane. Nearly all previous work on the mechanism of parasite lysis has been performed using TLF1. In this study, we directly test the hypothesis that TLF1 and TLF2 kill Trypanosoma brucei by a mechanism involving oxidative stress. We found no evidence for lipid peroxidation in trypanosomes exposed to high concentrations of trypanolytic HDL (impure TLF1), although lipid peroxidation was detected in parasites exposed to low concentrations of low molecular weight peroxides. Neither HDL, TLF1 nor TLF2 generated detectable levels of intracellular reactive oxygen intermediates. Various antioxidants also had no effect on TLF1 or TLF2-mediated lysis, although the antioxidants catalase and superoxide dismutase were effective at inhibiting peroxide generation and parasite lysis in control systems. Various metal chelating agents and protease inhibitors were also tested without effect. These data provide strong evidence against a peroxidative mechanism being involved in TLF-mediated lysis.  相似文献   
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Objectives

The aim of this study was to evaluate the angiographic efficacy and clinical outcomes of the Restore paclitaxel-coated balloon in a randomized trial designed to enable its approval with an indication for small-vessel disease (SVD).

Background

Higher rates of restenosis and stent thrombosis limit the effectiveness of drug-eluting stent (DES) treatment of SVD. Whether a drug-coated balloon (DCB)–only strategy is effective in de novo SVD is not yet established.

Methods

In the noninferiority RESTORE SVD China trial, eligible patients with reference vessel diameter ≥2.25 and ≤2.75 mm were randomized to the Restore DCB or the RESOLUTE Integrity DES in a 1:1 ratio stratified by diabetes and number of lesions treated. Patients with RVD ≥2.00 and <2.25 mm were enrolled in a nested very small vessel registry. Angiographic and clinical follow-up were planned at 9 months and 1 year, respectively, in all patients. The study was powered for the primary endpoint of 9-month in-segment percentage diameter stenosis.

Results

Between August 2016 and June 2017, a total of 230 subjects at 12 sites were randomized to the DCB group (n = 116) or DES group (n = 114); 32 patients were treated with the DCB in the very small vessel cohort. Nine-month in-segment percentage diameter stenosis was 29.6 ± 2.0% with the DCB versus 24.1 ± 2.0% with the DES; the 1-sided 97.5% upper confidence limit of the difference was 10.9%, achieving noninferiority of the DCB compared with the DES (p for noninferiority < 0.001). The DCB and DES had comparable 1-year rates of target lesion failure (4.4% vs. 2.6%, p = 0.72).

Conclusions

In this multicenter randomized trial, the Restore DCB was noninferior to the RESOLUTE DES for 9-month in-segment percentage diameter stenosis. (Assess the Efficacy and Safety of RESTORE Paclitaxel Eluting Balloon Versus RESOLUTE Zotarolimus Eluting Stent for the Treatment of Small Coronary Vessel Disease; NCT02946307)  相似文献   
15.

Objectives

The aim of the present study was to evaluate the angiographic efficacy, clinical safety, and effectiveness of the Restore paclitaxel-coated balloon in a randomized trial designed to enable the approval of the new device in China.

Background

Drug-coated balloon (DCB) angioplasty offers an effective treatment for in-stent restenosis. Restore is a new DCB with a SAFEPAX shellac-ammonium salt excipient that can avoid drug washing off during catheter delivery to the target lesion site.

Methods

In the noninferiority RESTORE ISR China (Compare the Efficacy and Safety of RESTORE DEB and SeQuent Please in Chinese Patient With Coronary In-stent Restenosis) trial, eligible patients with first occurrence of drug-eluting stent ISR were randomized to the Restore DCB or SeQuent Please DCB in a 1:1 ratio stratified by diabetes. Angiographic and clinical follow-up was planned at 9 months and 1 year, respectively, in all patients. The study was powered for the primary endpoint of 9-month in-segment late loss.

Results

Between May 2016 and July 2017, a total of 240 subjects at 12 sites were randomized to either the Restore group (n = 120) or the SeQuent Please group (n = 120). Nine-month in-segment late loss was 0.38 ± 0.50 mm with Restore versus 0.35 ± 0.47 mm with SeQuent Please; the 1-sided 97.5% upper confidence limit of the difference was 0.17 mm, achieving noninferiority of Restore compared with SeQuent Please (p for noninferiority = 0.02). Both DCBs had similar 1-year rates of target lesion failure (13.3% vs. 12.6%; p = 0.87).

Conclusions

In this head-to-head randomized trial, the Restore DCB was noninferior to the SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. (Compare the Efficacy and Safety of RESTORE DEB and SeQuent Please in Chinese Patient With Coronary In-stent Restenosis; NCT02944890)  相似文献   
16.
"泰淋方"对慢性肾盂肾炎大鼠肾小管功能的影响   总被引:1,自引:0,他引:1  
目的:评价"泰淋方"对慢性肾盂肾炎肾小管损伤的保护效应.方法:建立慢性肾盂肾炎大鼠模型,观察造模后及时给予"泰淋方"煎液(C组)对该模型30、60、90、120 d肾小管功能、肾皮质瘢痕发生率、肾功能、24 h尿蛋白定量、病理学的影响;以左旋氧氟沙星(D组)对照.结果:成功建立了CPN大鼠模型:(1)与模型组(B组)相比,C、D组能有效防止模型鼠在第90 d尿NAG/Cr的升高;实验期间各造模组肾功能、24 h尿蛋白与正常组(A组)无差异;(2)与B组相比,C、D组能显著减少模型二级及以上瘢痕率,但均不减少总体瘢痕率;(3)B组造模肾发生典型慢性间质性肾炎表现,对侧肾代偿性增大,C、D组总体病变减轻.结论:"泰淋方"能有效改善CPN大鼠伴随的肾小管功能减退和实质损伤,可能是治疗CPN的一种较好药物.  相似文献   
17.
分布于非洲的锥虫亚属布氏锥虫罗得西亚亚种和冈比亚亚种可感染人,引起人的非洲锥虫病,而布氏锥虫指名亚种、伊氏锥虫和马媾疫锥虫却不能感染人。人血清中的锥虫溶解因子和锥虫抗血清相关蛋白在其中起着关键作用。本文对人血清锥虫溶解因子和锥虫抗血清相关蛋白的研究进展进行了综述。  相似文献   
18.
目的 采用网络药理学方法,探讨桃莲绞复方(Tao-lian-jiao Formula,TLF)增强全成分肿瘤细胞疫苗(Vaccine)抗结直肠癌作用的分子机制.方法 观察TLF和全成分肿瘤细胞疫苗单用及联合使用对结肠癌CT26荷瘤小鼠体质量和肿瘤质量的影响,HE染色观察肿瘤组织病理变化.通过中药成分数据库(TCMSP、...  相似文献   
19.
目的:评价TLF、FOLFOX6与XELOX治疗进展期胃癌的成本效果。方法:收集中山大学附属肿瘤医院2004~2008年109例数据分为3组(TLF组50例,FOLFOX6组35例,XELOX组24例)。比较3组疗效,运用成本-效果分析法进行分析。结果:成本为医疗总费用时,TLF、FOLFOX6、XELOX的成本-效果比分别为167064.38、174876.61、164132.57,TLF、XELOX的增量成本-效果比分别为125960.22、146348.26;成本为总西药费时,TLF、FOLFOX6、XELOX的成本-效果比分别为125203.00、130233.67、135163.27,TLF、XELOX的增量成本-效果比分别为98734.07、143323.11。结论:成本为医疗总费用时,XELOX为最佳方案;成本为总西药费时,TLF为最合理方案。经济许可情况下,XELOX仍为最佳方案。  相似文献   
20.
BackgroundCompetitive flow from saphenous vein grafts (SVG) that remain patent following percutaneous coronary intervention (PCI) of the native vessel may compromise durability of the reconstructed vessel. SVG sacrifice has been advocated, but the safety and longer-term outcomes of this are unknown.MethodsWe retrospectively reviewed all post-bypass patients who following successful PCI of the native vessel underwent attempted saphenous vein graft (SVG) closure between January 2014 and July 2018 in two institutions. The co-primary end-points of interest were safety and target lesion failure (TLF), defined as a composite of cardiac death, target vessel recurrent myocardial infarction or clinically driven target lesion revascularisation (TLR).ResultsOf the 33 consecutive patients included, the reconstructed native vessel was a chronic total occlusion (CTO) in 93.9% of patients (n = 31) with a mean J-CTO score of 3.2 (±1.1) SVG closure was successful in 97.0% of patients (n = 32). Amplatzer Vascular Plugs (AVP; Abbott Vascular) were used in all patients with most grafts closed by a single plug (72.7%). The average procedure time was 20.1 min with evidence of a short learning curve. Over a mean follow up of 602 (±393) days from the date of SVG closure, the incidence of TLF was 9.1% (n = 3). There was an additional case of targe vessel failure (TVF) due to progression of native vessel disease not treated at the index procedure. SVG closure resulted in only 1 episode of “slow flow” that was transient and self-resolving. There were no other associated peri-procedural or in-hospital complications.ConclusionFollowing native vessel PCI, SVG sacrifice may be considered to terminate the potentially deleterious effects of residual competitive flow. In selected cases, this approach achieves high success rate and favourable longer-term outcomes.  相似文献   
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