Polylysine-Immobilized Chitosan Beads as Adsorbents for Bilirubin

Hyperbilirubinemia generally relates to an elevated bilirubin level in the blood and is usually an indication of a disease of the blood, liver, or biliary tract. Hemoperfusion using synthetic resins as sorbents has been one of the ways to reduce bilirubin. In this study, chitosan, a natural polysaccharide having structural characteristics similar to glycosaminoglycans and which is nontoxic and biocompatible, has been used for bilirubin binding. Several layers of poly-L-lysine have been coated covalently onto chitosan beads, using N2 plasma and carbodiimide treatments. Such surface-modified chitosan beads exhibited high binding affinities for bilirubin (1.13 +/- 0.18 mg/g beads) in aqueous phosphate buffer solutions at 4 degrees C in relation to activated charcoal (0.74 +/- 0.2 mg/g). The polylysine-coated resins have been reported to have an improved binding affinity for bilirubin over cholestyramine. It seems that the surface-immobilized polylysine has an increased bilirubin binding affinity and is highly stable. The binding capacity is proportional to the amount of polylysine bonded to the chitosan beads. The hemolytic potential of all modified beads is compatible with polystyrene control tubes. Studies were also performed against albumin as proof of specificity toward bilirubin binding. The albumin-coated beads have shown the highest blood compatibility and selectivity over the other modified beads. However, it appears that polylysine-modified chitosan may be an excellent sorbent system for hemoperfusion due to its high binding affinity, capacity, and blood compatibility. Further studies are needed to determine its behavior under clinical conditions.     

Quantitative characterization of magnetic separators: Comparison of systems with and without integrated microfluidic mixers

We present two new types of microfluidic passive magnetic bead separator systems as well as methods for performing quantitative characterizations of them. Both systems consist of a microfluidic channel with long rectangular magnetic elements of permalloy that are placed by the sides of the channel and magnetized by an external magnetic field. In one of the systems, a staggered herringbone microfluidic mixer is integrated in the channel. The characterization of the systems includes magnetic measurements of the capture-and-release efficiencies, estimates of distributions of captured beads in a channel from micrographs, and simulations and analytical models of bead trajectories, capture efficiencies, and capture distributions. We show that the efficiencies of both systems compare favorably to those in the literature. For the studied geometries, the mixer is demonstrated to increase the bead capture-and-release efficiency for a fixed flow rate by up to a factor of two. Moreover, high capture efficiencies can be achieved in the system with mixer at up to ten times higher flow rates than in the system without mixer.     

Time-programmed pulsatile release of dextran from calcium-alginate gel beads coated with carboxy-n-propylacrylamide copolymers.

Time-programmed release of macromolecular drugs was achieved by utilization of calcium-alginate gel beads modified with coated copolymer layers. Modified calcium-alginate gel beads coated with poly(carboxy-n-propylacrylamide-co-dimethylacrylamide) [poly(CNPAAm-co-DMAAm)] (22.7 mol% of CNPAAm) of varying coating thickness from 25 to 125 μm were developed as drug carriers. Model macromolecular drugs used were fluorescein isothiocyanate (FITC)-labeled dextrans with different molecular weights ranging from 9400 to 145 000. FITC-dextran release was strongly dependent on both copolymer coating thicknesses and the dextran molecular weights. Release of FITC-dextran (MW 9400) followed Fickian diffusion according to t^1/2 dependence, indicating that the drug diffusion is the main driving force for release of dextran MW 9400. Release of higher molecular weight FITC-dextrans (71 200 and 145 000) exhibited a burst-effect preceded by a preset lag time. These release profiles were governed by the dissociation of calcium ions from polyguluronate sequences in alginate molecules along with the diffusion of sodium ions into the gel bead core. This created osmotic pressure inside the gel, inducing breakage of the coated copolymer layer and accelerated drug release. Burst release of macromolecular drugs thus occurred after a certain lag period. The lag time was regulated by the copolymer coat thickness. A pulsatile release of FITC-dextran was demonstrated by combining a series of modified alginate gel beads in a single batch.     

缓释厄贝沙坦涂层支架置入对内膜增生的影响

目的:探讨缓释厄贝沙坦涂层支架置入对内膜增生的影响。方法:建立冠状动脉支架置入的广西种的微型猪动物模型,分别置入普通裸支架和缓释厄贝沙坦涂层支架。于支架置入后3、7、28、90和180d截取支架段血管连同邻近的近端正常血管段,通过病理组织学分析和聚合酶链反应技术检测支架局部内膜增生情况。结果:正常血管段表达PCNAmRNA在各个时间段差异没有显著性。普通支架置入后3d局部血管壁PCNAmRNA的表达明显增高,并在术后7d达到高峰。术后90dPCNAmRNA的表达呈现下降的趋势,但仍显著高于正常血管段,并且差异一直持续到术后180d。术后第3天药物支架段PCNAmRNA的表达明显增高,并在术后7d达到高峰。术后7d药物支架段PCNAmRNA的表达已显著低于普通支架段,并且差异一直持续到术后90d。术后90～180d药物支架段内膜加中膜面积明显小于普通支架段。结论:缓释厄贝沙坦涂层支架置入可在一定程度上减少支架置入后内膜的增生反应。     

男性急性冠状动脉综合征患者药物洗脱支架治疗后吸烟状态对临床预后的影响

目的:本研究旨在探讨急性冠状动脉综合征(ACS)患者药物洗脱支架治疗后戒烟的依从性及吸烟状态对术后长期临床预后的影响。方法:调查656例接受药物洗脱支架治疗的男性ACS患者术前及术后吸烟状态,根据术后的吸烟状态将患者分为3组:不吸烟组(n=226)、戒烟组(n=283)及目前吸烟组(n=147),详细记录随访时主要不良心脑事件(MACCE)的发生情况。采用Cox多元回归分析吸烟状态对主要不良心脑事件的影响。结果:平均随访27个月,656例患者术前吸烟率为65.5%,术后吸烟率为22.4%,吸烟组患者较年轻(P0.001),血脂异常较多(P=0.005),文化水平较低(P0.001);与不吸烟组和戒烟组相比,吸烟组全因性死亡(1.8%vs 1.1%vs 6.1%,P=0.004)和主要不良心脑事件(7.1%vs 5.3%vs 15.0%,P=0.002)的发生率较高,Cox多元回归分析显示:术后吸烟是主要不良心脑事件[比值比(HR)=1.404,95%可信区间(CI):1.206~1.793;P=0.008]发生的独立危险因素。结论:男性ACS患者药物洗脱支架治疗后吸烟是导致术后发生主要不良心脑事件的独立危险因素。     

Impact of Coronary Plaque Characteristics on Late Stent Malapposition after Drug-Eluting Stent Implantation

Purpose

To evaluate the impact of pre-procedural coronary plaque composition assessed by virtual histology intravascular ultrasound (VH-IVUS) on late stent malapposition assessed by optical coherence tomography (OCT) following drug-eluting stent (DES) implantation.

Materials and Methods

The study population consisted of 121 patients (121 lesions) who underwent both pre-procedural VH-IVUS and follow-up OCT after DES implantation. The association between pre-procedural plaque composition [necrotic core (NC), dense calcium (DC), fibrotic (FT), and fibro-fatty (FF) volumes] assessed by VH-IVUS and late stent malapposition (percent malapposed struts) or strut coverage (percent uncovered struts) assessed by follow-up OCT was evaluated.

Results

Pre-procedural absolute total NC, DC, FT, and FF plaque volumes were 22.9±19.0, 7.9±9.6, 63.8±33.8, and 16.5±12.4 mm³, respectively. At 6.3±3.1 months post-intervention, percent malapposed and uncovered struts were 0.8±2.5% and 15.3±16.7%, respectively. Pre-procedural absolute total NC and DC plaque volumes were positively correlated with percent malapposed struts (r=0.44, p<0.001 and r=0.45, p<0.001, respectively), while pre-procedural absolute total FT plaque volume was weakly associated with percent malapposed struts (r=0.220, p=0.015). Pre-procedural absolute total DC plaque volume was the only independent predictor of late stent malapposition on multivariate analysis (β=1.12, p=0.002). There were no significant correlations between pre-intervention plaque composition and percent uncovered struts.

Conclusion

Pre-procedural plaque composition was associated with late stent malapposition but not strut coverage after DES implantation. Larger pre-procedural absolute total DC plaque volumes were associated with greater late stent malapposition.     

Transarterial chemoembolization with pirarubicin-eluting microspheres in patients with unresectable hepatocellular carcinoma: Preliminary results

PurposeTo present the early results of pirarubicin-eluting microsphere transarterial chemoembolization (PE-TACE) for patients with unresectable hepatocellular carcinoma (HCC).Materials and methodsWe retrospectively analyzed 55 consecutive patients with HCC who received PE-TACE between April 1, 2015 and August 30, 2016. The complication rate, tumor response rate, progression-free survival (PFS), and overall survival (OS) were analyzed.ResultsAdverse events were generally mild and included abdominal pain and fever, although a major complication was reported in 1 patient (1.8%). During a median follow-up of 10.0 months (range, 3.0–24.0 months), 14 patients (25.5%) achieved a complete tumor response, 25 (45.5%) had a partial response, 9 (16.4%) showed stable disease, and 7 (12.7%) had disease progression. The 1-month overall response rate was 70.9%, and the local tumor response rate was 89.0%. The 1-month tumor response rate was 100% for Barcelona Clinic Liver Cancer (BCLC) stage A or B disease and 62.8% for BCLC stage C disease. The median PFS was 6.1 months (95% confidence interval [95%CI], 3.4–8.8 months; range, 1.0–24.0 months). The median OS was 11.0 months (95%CI, 7.1–14.9 months; range, 2.0–24.0 months). Kaplan-Meier analysis (log-rank test) found significant differences in OS between patients grouped by tumor number (P = 0.006), tumor size (P = 0.035), and Eastern Cooperative Oncology Group (ECOG) score (P = 0.005). The tumor number (1 vs. ≥2) was the only factor independently associated with OS (hazard ratio [HR], 2.867; 95%CI, 1.330–6.181; P = 0.007).ConclusionsPE-TACE for unresectable HCC may be safe, with favorable tumor response rates and survival time, especially in patients with a single large tumor. Longer follow-up using a larger series is necessary to confirm these preliminary results.     

不同磁珠对致病菌吸附性能的比较研究

目的通过对裸磁珠、单一抗体和混合抗体包被的免疫磁珠的吸附性能的比较,建立一种快速、同时富集多种致病菌的方法。方法通过沉淀法制备Fe3O4磁珠,对其进行表面修饰,用抗体进行偶联制备成免疫磁珠,比较不同磁珠对致病菌的吸附性能。结果通过化学合成和修饰的方法制备出裸磁珠和Fe3O4/SiO2的免疫磁珠。免疫磁珠对细菌的吸附率与裸磁珠比较差异显著(t=7.55,P<0.05),平均吸附率分别为96.62%和80.89%。通过洗涤优化,免疫磁珠对目标菌的吸附率从97.03%降到93.67%,对非目标菌的吸附率从53.33%降到16.67%;裸磁珠对目标菌和非目标菌的吸附率从81%降到13.33%;免疫磁珠对单一菌和混合菌的吸附性能无显著差异(P=0.427)。结论单一抗体和混合抗体包被的免疫磁珠能特异性富集目标菌,通过富集程序优化可以达到良好的吸附效果。     

Angiographic and clinical outcome for the treatment of in-stent restenosis with sirolimus-eluting stent compared to vascular brachytherapy

Summary Background With the use of coronary stents for the treatment of coronary artery disease, in-stent restenosis became a major clinical problem. In this non-randomized study, we examined the use of stent-based delivery of sirolimus (rapamycin) for the treatment of in-stent restenosis in comparison to intracoronary -brachytherapy, regarding the clinical effectiveness and the angiographic results for the treatment of in-stent restenosis after 6–9 months. Methods and results Between July 2001 and May 2002, 28 patients (65±11 years) with instent restenosis were treated with intracoronary brachytherapy. Consecutively, between May 2002 and April 2003, 28 patients (65±10 years) with in-stent restenosis were treated with the implantation of a sirolimus-eluting stent (SES). Patients with in-stent restenosis treated by implantation of a SES had significantly lower incidence of in-stent restenosis (1/28 (3.6%) vs 10/28 (36%); p=0.007) and insegment restenosis (4/28 (14%) vs 14/28 (50%); p=0.013) compared to patients treated with brachytherapy. Target lesion and target vessel revascularization rate tended to be lower in the SES group (14 vs 25%) but did not yet reach statistical significance. One patient died in the group treated by implantation of a SES eight months after stenting, one patient suffered from myocardial infarction due to a subtotal in-stent restenosis after brachytherapy. Two patients after brachytherapy underwent surgical revascularization due to recurrent in-stent restenosis similar to the patient with in-stent restenosis after SES implantation. Conclusion In this study we show the feasibility and safety of the treatment of in-stent restenosis by implantation of sirolimus-eluting stents and demonstrate a lower incidence of recurrent in-stent restenosis as well as lower late luminal loss compared to treatment by intravascular brachytherapy.

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