Mechanisms of 8‐aminoquinoline induced haemolytic toxicity in a G6PDd humanized mouse model

Primaquine (PQ) and Tafenoquine (TQ) are clinically important 8‐aminoquinolines (8‐AQ) used for radical cure treatment of P. vivax infection, known to target hepatic hypnozoites. 8‐AQs can trigger haemolytic anaemia in individuals with glucose‐6‐phosphate dehydrogenase deficiency (G6PDd), yet the mechanisms of haemolytic toxicity remain unknown. To address this issue, we used a humanized mouse model known to predict haemolytic toxicity responses in G6PDd human red blood cells (huRBCs). To evaluate the markers of eryptosis, huRBCs were isolated from mice 24–48 h post‐treatment and analysed for effects on phosphatidylserine (PS), intracellular reactive oxygen species (ROS) and autofluorescence. Urinalysis was performed to evaluate the occurrence of intravascular and extravascular haemolysis. Spleen and liver tissue harvested at 24 h and 5–7 days post‐treatment were stained for the presence of CD169+ macrophages, F4/80+ macrophages, Ter119+ mouse RBCs, glycophorin A+ huRBCs and murine reticulocytes (muRetics). G6PDd‐huRBCs from PQ/TQ treated mice showed increased markers for eryptosis as early as 24 h post‐treatment. This coincided with an early rise in levels of muRetics. Urinalysis revealed concurrent intravascular and extravascular haemolysis in response to PQ/TQ. Splenic CD169+ macrophages, present in all groups at day 1 post‐dosing were eliminated by days 5–7 in PQ/TQ treated mice only, while liver F4/80 macrophages and iron deposits increased. Collectively, our data suggest 8‐AQ treated G6PDd‐huRBCs have early physiological responses to treatment, including increased markers for eryptosis indicative of oxidative stress, resulting in extramedullary haematopoiesis and loss of splenic CD169+ macrophages, prompting the liver to act as the primary site of clearance.     

UVC fluencies for preventative treatment of Pseudomonas aeruginosa contaminated polymer tubes

Exposing Pseudomonas aeruginosa biofilm grown on the inner surface of Teflon and silicone tubes to UVC light (265 nm) from light emitting diodes (LED) has previously been shown to substantially reduce biofilm growth. Smaller UVC fluencies were required to disinfect Teflon tubes compared to silicone tubes. Light propagation enhancement in tubes can be obtained if the refractive index of the intra-luminal saline solution is higher than that of the polymer. This condition is achieved by using Teflon tubes with a low refractive index (1.34) instead of the polymers with a high refractive index (1.40–1.50) normally used for tubing in catheter production. Determining whether or not UVC light exposure can disinfect and maintain the intra-luminal number of colony forming units (CFUs) at an exceedingly low level and thus avoid the growth and establishment of biofilm is of interest. The use of UVC diodes is demonstrated to be a preventative disinfection treatment on tubes made of Teflon, which enhances the UVC light propagation, and on tubes made of a softer material, ethylene vinyl acetate (EVA), which is suitable for catheters but much less suitable for UVC light propagation. Simulating an aseptic breach (～10³–10⁴ CFU ml^?1), the UVC disinfection set-up was demonstrated using tubes contaminated with planktonic P. aeruginosa. After the tubes (10–20 cm) were inoculated with the bacterial solution for 3 h, they were emptied and filled with saline solutions (0.9–20%). Next UVC fluencies (0–21 mJ cm^?2) were applied to the tubes 3 h after inoculation. Colony counts were carried out on liquid samples drawn from the tubes the first day after UVC treatment and liquid and surface samples were collected and analyzed 3–4 days later. A fluence of approximately 1.0 mJ cm^?2 was noted as being sufficient for no growth for a period of 3–4 days for the Teflon tubes. Determining the fluence threshold for the EVA tubes was not possible. Almost all of the UVC-treated EVA tubes were disinfected simply by filling the tubes with a saline solution. Direct UVC treatment of the contaminated EVA tubes revealed, however, that a fluence of 21 mJ cm^?2 killed the bacteria present in the tubes and kept them disinfected for a period of 3–4 days.     

Update on the challenging role of biofilms in peritoneal dialysis

Biofilms are commonly associated with an increased risk of patient infection. In peritoneal dialysis (PD), catheter associated infection, especially peritonitis, remains a clinically relevant problem. Although the presence of a biofilm is recognized in relapsing, repeat, and catheter-related peritonitis, it remains poorly characterized. In this review, an update on the role of biofilms in PD infections is presented. The emerging concept that host cells and tissue associated biofilms, in addition to the biofilms on the catheters themselves, contribute to the recalcitrance of infections is discussed. Furthermore, the evidence of biofilms on PD catheters, their developmental stages, and the possible influence of the PD environment are reviewed. The focus is given to ex vivo and in vitro studies that contribute to the elucidation of the interplay between host, microbial, and dialysis factors. The key issues that are still to be answered and the challenges to clinical practice are discussed.     

Intravascular magnetomotive optical coherence tomography of targeted early‐stage atherosclerotic changes in ex vivo hyperlipidemic rabbit aortas

We report the development of an intravascular magnetomotive optical coherence tomography (IV‐MM‐OCT) system used with targeted protein microspheres to detect early‐stage atherosclerotic fatty streaks/plaques. Magnetic microspheres (MSs) were injected in vivo in rabbits, and after 30 minutes of in vivo circulation, excised ex vivo rabbit aorta samples specimens were then imaged ex vivo with our prototype IV‐MM‐OCT system. The alternating magnetic field gradient was provided by a unique pair of external custom‐built electromagnetic coils that modulated the targeted magnetic MSs. The results showed a statistically significant MM‐OCT signal from the aorta samples specimens injected with targeted MSs.

Representative magnetomotive signal (green) using targeted and non‐targeted magnetomotive microspheres in atherosclerotic diseased rabbit aortas.     

Protection of catheter surfaces from adhesion of Pseudomonas aeruginosa by a combination of silver ions and lectins

A catheter surface was modified by coating a cellulose acetate polymer. Adhesion of Pseudomonas aeruginosa ATCC 27853 to the surface was investigated by exposing bacterial cultures to three treatments: polymer impregnated with silver ions (Ag⁺), polymer surfaces coated with lectins and a combination of Ag⁺ and a lectin coating. The effective concentration of Ag⁺ providing protection against bacterial biofilm development was 100g/ml and higher. Lectins alone at 10% also showed inhibition of bacterial attachment. However, the best result was achieved against bacterial adhesion and growth on surfaces using a combination of 100 g Ag⁺/ml and a lectin coating as a surface treatment. This surface treatment was also effective against both fresh culture and a two-week-old culture containing P. aeruginosa producing exopolymers. Our results suggest that Ag⁺impregnation combined with a lectin coating warrants further investigation as a potential means of protecting catheters.     

导管射频消融治疗特发性室性心动过速的体会

目的探讨应用导管射频消融（ＲＦＣＡ）治疗特发性室性心动过速的疗效。方法经皮穿刺左右侧股静脉右侧股动脉（起源于左室时）,将多根６Ｆ或７Ｆ４极导管送至高位右房（ＨＲＡ）、房束（ＨＢＥ）、右室心尖（ＲＶＡ）、右室流出道（ＲＶＯＴ）或左室（ＬＶ）,作短阵快速和程序刺激心室诱发ＶＴ,同步记录１２导联及心腔内各部位电图。结果除１例不能坚持ＲＦＣＡ外,成功１１例（９１．７％）,另１例因疗效不满意改用导管心内膜直流电消融而获成功。结论术前诊断及靶点标测的准确性是ＲＦＣＡ治疗成功的关键。     

超声引导下经皮穿刺置管引流治疗重症急性胰腺炎急性胰周液体积聚的临床疗效

目的:探讨超声引导下经皮穿刺置管引流(PCD)治疗重症急性胰腺炎(SAP)急性胰周液体积聚的的临床疗效。方法:收集2009年3月~2013年10月我院收治的经临床确定的SAP急性胰周液体积聚患者51例,按随机数字表法分为观察组(26例)和对照组(25例),观察组患者给予超声引导下经皮穿刺置管引流术治疗,对照组采用剖腹引流的经典引流。比较两组患者血淀粉酶恢复至时间、住院时间、治愈率、并发症发生率。结果:观察组血淀粉酶恢复时间及住院时间均小于对照,差异有统计学意义(P0.05);观察组患者总有效率位96.2%(25/26),高于对照组的68.0%(17/25),两组比较组间差异有统计学意义(P0.05);观察组治疗后病死、腹腔出血、胰瘘发生率高于对照组(均P0.05);两组脓毒症及多器官功能障碍综合症(MODS)的比较差异无统计学差异(P0.05)结论:超声引导下经皮穿刺置管引流术治疗SAP急性胰周液体积聚效果良好,并发症的低,安全可靠,具有较大的临床推广价值。     

中心静脉导管引流对单孔胸腔镜肺癌根治术患者术后胸腔引流的应用分析

目的:探讨中心静脉导管引流对单孔胸腔镜肺癌根治术患者术后胸腔引流的应用效果。方法:回顾性选取2019年1月至2019年12月期间我院收治的行单孔胸腔镜肺癌根治术患者80例的临床资料,根据引流方式的不同分为A组(n=40,传统引流)和B组(n=40,中心静脉导管引流),对比两组患者临床指标、生活质量、炎性因子及并发症发生情况。结果:B组引流操作时间、术后住院时间短于A组(P0.05)。两组术后3个月生活质量简表(SF-36)各维度评分均较术前升高,且B组高于A组(P0.05)。两组术前、术后3d、术后7d白介素-6(IL-6)、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)呈先升高后下降趋势,且术后3d、术后7d B组以上指标低于A组(P0.05)。两组术后并发症发生率比较无差异(P0.05)。结论:与传统引流相比,单孔胸腔镜肺癌根治术患者术后采用中心静脉导管引流,效果显著,可减少炎性刺激,安全可靠,有效改善患者术后生活质量。