Patient Experience and Preference in Transradial versus Transfemoral Access during Transarterial Radioembolization: A Randomized Single-Center Trial

Purpose

To determine patient preference for transradial access (TRA) or transfemoral access (TFA) after experiencing both.

Supersaturated polymeric micelles for oral cyclosporine A delivery

Polymeric micelles provide a promising platform for improving oral absorption of poorly soluble drugs. However, improved understanding of how drug retention within the hydrophobic micelle core can reduce drug absorption is required. We designed supersaturated polymeric micelles (Super-PMs) to increase molecularly dissolved drug concentration and gain an insight into the effect of the degree of supersaturation on oral absorption of cyclosporine A (CsA) in rats. The drug release from Super-PMs increased with an increase in initial supersaturation degrees in micelles. The cellular uptake of coumarin-6 was reduced by the retention of drug in polymer micelles. The transport flux of CsA across Caco-2 monolayer was increased with initial supersaturation degrees of 0.81–3.53 (p < 0.05). However, increase in supersaturation to 5.64 actually resulted in decreased CsA transport. The same trend was observed in a rat in vivo absorption study, in which the highest bioavailability of 134.6 ± 24.7% (relative to a commercial product, Sandimmun Neoral®, p < 0.01) was achieved when the supersaturation degree was 3.53. These results demonstrated that Super-PMs were a promising drug delivery system for compounds with low aqueous solubility. This study also provided an experimental proof for the hypothesis that moderately supersaturated formulations are valuable alternative to high supersaturation formulations, resulting in optimal in vivo performance, and the degree of supersaturation should be carefully controlled to optimize drug absorption.     

经皮股动脉导管药盒系统介入治疗肝细胞癌的临床应用

目的探讨经皮股动脉导管药盒系统介入治疗肝细胞癌的临床疗效及并发症。方法从1999年1月到2001年3月应用经皮股动脉植入导管药盒系统（PCS）对45例肝细胞癌患者进行化疗和碘油栓塞治疗，回顾性分析临床疗效及并发症。结果PCS介入治疗肝细胞癌的有效率为66．7％（30／45）。患者1、2、3年生存率为75．6％（34／45），33．3％（15／45），17．8％（8／45）。弪皮股动脉导管药盒植入术的并发症包括1例切口感染及切口延迟愈合，4例PCS堵塞和1例留置导管尖移位。所有并发症经适当处理后无严重后遗症。结论经皮股动脉导管药盒系统植入术对介入治疗肝细胞性肝癌是1种安全有效技术。     

Effects of subacute and chronic lead treatment on glucose homeostasis and renal cyclic AMP metabolism in rats

The effects of chronic oral ingestion of lead in doses ranging from 20–80 ppm were compared with those seen after the subacute exposure of rats to a 10 mg/kg daily dose of the heavy metal for 7 days. Irrespective of the treatment regimen used, lead treatment significantly increased the activities of renal pyruvate carboxylase, phosphoenopyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase. The observed enhancement of kidney gluconeogenic enzymes in chronically treated animal was associated with a stimulation of the adenylate cyclase-cyclic AMP system, a rise in blood glucose and urea as well as a depression in hepatic glycogen and serum immunoreactive insulin (IRI) levels. In contrast, subacute exposure to lead failed to significantly alter cyclic AMP metabolism and the concentrations of liver glycogen, blood glucose, serum urea or IRI. Whereas the insulinogenic index (the ratio of serum IRI to blood concentration) was markedly suppressed in chronically treated rats, this ratio remained within normal limits following subacute exposure to the heavy metal. However, a marked decrease in the insulinogenic index was observed in subacutely treated rats 15 min after the administration of a glucose load. The data provide evidence to show that increased glucose synthesis as well as suppressed pancreatic function may be responsible for lead-induced disturbances in glucose homeostasis.     

超选择动脉插管与导管药盒系统化疗对中晚期宫颈癌疗效的对比研究

目的探讨植入式导管药盒化疗与髂内动脉插管介入化疗对中晚期宫颈癌的疗效。方法中晚期宫颈癌患者81例．随机分为动脉药盒组（PCS）（治疗组）和介入栓塞组（TACE）（对照组）,手术或放疗前分别给予PCS和TACE化疗。结果（1）治疗组和对照组病人近期临床总有效率分别为90．0％、70．73％;手术率分别为85．0％、65．85％;骨髓抑制和胃肠道毒副反应分别为37．5％、67.3％和61．0％、87．8％;治疗费用及住院时间两组比较．差异有统计学意义（P〈0．05）。（2）两组病人复发率及生存率分别比较,差异无统计学意义（P〉0．05）。结论PCS栓塞化疗治疗中晚期宫颈癌近期有效率明显提高,毒副作用减少,具有广阔的应用前景。     

Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: investigation of nicotinic acid receptor agonists

An investigative renal toxicity study using metabolomics was conducted with a potent nicotinic acid receptor (NAR) agonist, SCH 900424. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques were used to identify small molecule biomarkers of acute kidney injury (AKI) that could aid in a better mechanistic understanding of SCH 900424-induced AKI in mice. The metabolomics study revealed 3-indoxyl sulfate (3IS) as a more sensitive marker of SCH 900424-induced renal toxicity than creatinine or urea. An LC-MS assay for quantitative determination of 3IS in mouse matrices was also developed. Following treatment with SCH 900424, 3IS levels were markedly increased in murine plasma and brain, thereby potentially contributing to renal- and central nervous system (CNS)-related rapid onset of toxicities. Furthermore, significant decrease in urinary excretion of 3IS in those animals due to compromised renal function may be associated with the elevation of 3IS in plasma and brain. These data suggest that 3IS has a potential to be a marker of renal and CNS toxicities during chemically-induced AKI in mice. In addition, based on the metabolomic analysis other statistically significant plasma markers including p-cresol-sulfate and tryptophan catabolites (kynurenate, kynurenine, 3-indole-lactate) might be of toxicological importance but have not been studied in detail. This comprehensive approach that includes untargeted metabolomic and targeted bioanalytical sample analyses could be used to investigate toxicity of other compounds that pose preclinical or clinical development challenges in a pharmaceutical discovery and development.     

High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: Quality by design optimization and characterization

Poly(dl-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery of biopharmaceuticals owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The purpose of this study was to understand and define optimal parameters for preparation of small interfering RNA (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation method and characterize their properties. The experiments were performed according to a 2⁵⁻¹ fractional factorial design based on five independent variables: The volume ratio between the inner water phase and the oil phase, the PLGA concentration, the sonication time, the siRNA load and the amount of acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency and the particle size were investigated. The most important factors for obtaining an encapsulation efficiency as high as 70% were the PLGA concentration and the volume ratio whereas the size was mainly affected by the PLGA concentration. The viscosity of the oil phase was increased at high PLGA concentration, which explains the improved encapsulation by stabilization of the primary emulsion and reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased the encapsulation efficiency at low PLGA concentrations. The PLGA matrix protected siRNA against nuclease degradation, provided a burst release of surface-localized siRNA followed by a triphasic sustained release for two months. These results enable careful understanding and definition of optimal process parameters for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with immediate and long-term sustained release properties.     

动脉药盒植入系统治疗肝癌发生堵塞的预防与处理

目的探讨动脉药盒植入系统治疗肝癌发生堵塞的预防与处理方法。材料与方法107例晚期肝癌患者行介入手术经皮经股动脉或经皮经锁骨下动脉于肝固有动脉内植入动脉药盒系统107个,进行随访,主要对动脉药盒系统堵塞的发生情况进行观察并总结预防与处理方法。结果动脉药盒系统植入术后的发生堵塞有8个,发生率为7.48%（8/107）,经肝素生理盐水溶液冲洗动脉药盒系统或/和高浓度尿激酶溶液动脉药盒系统内推注（部分在胃肠X光机或DSA机下进行）后复通率为75.00%（6/8）。结论在胃肠X光机或DSA机下进行肝素生理盐水溶液冲洗动脉药盒系统或/和高浓度尿激酶溶液动脉药盒系统内推注是处理堵塞的有效办法。