Uremic Toxins: Removal with Different Therapies

A convenient way to classify uremic solutes is to subdivide them according to the physicochemical characteristics influencing their dialytic removal into small water‐soluble compounds (<500 Da), protein‐bound compounds, and middle molecules (>500 Da). The prototype of small water‐soluble solutes remains urea although the proof of its toxicity is scanty. Only a few other water‐soluble compounds exert toxicity (e.g., the guanidines, the purines), but most of these are characterized by an intra‐dialytic behavior, which is different from that of urea. In addition, the protein‐bound compounds and the middle molecules behave in a different way from urea, due to their protein binding and their molecular weights, respectively. Because of these specific removal patterns, it is suggested that new approaches of influencing uremic solute concentration should be explored, such as specific adsorptive systems, alternative dialytic timeframes, removal by intestinal adsorption, modification of toxin, or general metabolism by drug administration. Middle molecule removal has been improved by the introduction of large pore, high‐flux membranes, but this approach seems to have come close to its maximal removal capacity, whereas multicompartmental behavior might become an additional factor hampering attempts to decrease toxin concentration. Hence, further enhancement of uremic toxin removal should be pursued by the introduction of alternative concepts of elimination.     

Back to the Future: Middle Molecules, High Flux Membranes, and Optimal Dialysis

Middle molecules can be defined as compounds with a molecular weight (MW) above 500 Da. An even broader definition includes those molecules that do not cross the membranes of standard low‐flux dialyzers, not only because of molecular weight, but also because of protein binding and/or multicompartmental behavior. Recently, several of these middle molecules have been linked to the increased tendency of uremic patients to develop inflammation, malnutrition, and atheromatosis. Other toxic actions can also be attributed to the middle molecules. In the present publication we will consider whether improved removal of middle molecules by large pore membranes has an impact on clinical conditions related to the uremic syndrome.
The clinical benefits of large pore membranes are reduction of uremia‐related amyloidosis; maintenance of residual renal function; and reduction of inflammation, malnutrition, anemia, dyslipidemia, and mortality. It is concluded that middle molecules play a role in uremic toxicity and especially in the processes related to inflammation, atherogenesis, and malnutrition. Their removal seems to be related to a better outcome, although better biocompatibility of membranes might be a confounding factor.     

Uremic pleuritis in chronic hemodialysis patients

Chronic hemodialysis (HD) patients are predisposed to several complications associated with pleural effusion. In addition, uremia can directly cause pleuritis. However, there are inadequate data about pathogenesis and natural course of uremic pleuritis. In this study, 76 chronic HD patients with pleural effusion admitted to the Respiratory Center of Masih Daneshvari Hospital, in Tehran, Iran between June 2005 and May 2011 were evaluated to figure out the etiology of their pleural disease. Among these patients, patients with uremic pleuritis were identified and studied. The rate of uremic pleuritis was 23.7%. Other frequent etiologies of pleural effusion were parapneumonic effusion (23.7%), cardiac failure (19.7%), tuberculosis (6.6%), volume overload, malignancy, and unknown. In patients with uremic pleuritis, dyspnea was the most common symptom, followed by cough, weight loss, anorexia, chest pain, and fever. Compared to patients with parapneumonic effusion, patients with uremic effusion had a significantly higher rate of dyspnea and lower rate of cough and fever. Pleural fluid analysis showed that these patients had a significantly lower pleural to serum lactic dehydrogenase ratio, total pleural leukocytes, and polymorphonuclear count compared to patients with parapneumonic effusion. Improvement was achieved in 94.1% of patients with uremic pleuritis by continuation of HD, chest tube insertion or pleural decortication; an outcome better than the previous reports. Despite the association with an exudative effusion, inflammatory pleural reactions in patients with uremic pleuritis may not be as severe as infection‐induced effusions. Owing to the advancement in HD technology and other interventions, outcome of uremic pleuritis may be improved.     

The Progression of Uremic Polyneuropathy in Patients on Hemodialysis and Hemofiltration: A Two‐Year Study

Uremic polyneuropathy is one of the major complications of long‐term end‐stage renal disease. In the present study, we performed an electrophysiologic evaluation in 17 patients having a mean age of 49 ± 11 years. The patients were divided into two groups according to dialysis method. Group A included 9 patients who were undergoing conventional hemodialysis (mean age, 44.2 ± 12.5 years; mean duration on dialysis, 21.7 ± 4.3 months); group B included 8 patients undergoing hemofiltration (mean age, 55.2 ± 5.2 years; mean duration on treatment, 27 ± 7.6 months). Measurements of the distal latency time of the sensory fibers (median, ulnar, and sural nerves), and measurements of the distal latency time and peripheral conduction velocity of the motor fibers (median and peroneal nerves) were performed. In addition, we recorded somatosensory evoked potentials after peripheral stimulation of the median and peroneal nerves. The electrophysiologic evaluations were repeated two times at intervals of 12 months. In group A, a statistically significant worsening of motor and sensory conductance in the upper and lower limbs was observed; in group B, a statistically significant improvement was found. These findings suggest that hemofiltration has a more beneficial effect on motor and sensory conductivity than does conventional hemodialysis.     

History of hemodialyzers' designs

Accumulation of knowledge requisite for development of hemodialysis started in antiquity and continued through Middle Ages until the 20th century. Firstly, it was determined that the kidneys produce urine containing toxic substances that accumulate in the body if the kidneys fail to function properly; secondly, it was necessary to discover the process of diffusion and dialysis; thirdly, it was necessary to develop a safe method to prevent clotting in the extracorporeal circulation; and fourthly, it was necessary to develop biocompatible dialyzing membranes. Most of the essential knowledge was acquired by the end of the 19th century. Hemodialysis as a practical means of replacing kidney function started and developed in the 20th century. The original hemodialyzers, using celloidin as a dialyzing membrane and hirudin as an anticoagulant, were used in animal experiments at the beginning of the 20th century, and then there were a few attempts in humans in the 1920s. Rapid progress started with the application of cellophane membranes and heparin as an anticoagulant in the late 1930s and 1940s. The explosion of new dialyzer designs continued in the 1950s and 1960s and ended with the development of capillary dialyzers. Cellophane was replaced by other dialyzing membranes in the 1960s, 1970s, and 1980s. Dialysis solution was originally prepared in the tank from water, electrolytes, and glucose. This solution was recirculated through the dialyzer and back to the tank. In the 1960s, a method of single-pass dialysis solution preparation and delivery system was designed. A large quantity of dialysis solution was used for a single dialysis. Sorbent systems, using a small volume of regenerated dialysis solution, were developed in the mid 1960s, and continue to be used for home hemodialysis and acute renal failure. At the end of the 20th century, a new closed system, which prepared and delivered ultrapure dialysis solution preparation, was developed. This system also had automatic reuse of lines and dialyzers and prepared the machine for the next dialysis. This was specifically designed for quotidian home hemodialysis. Another system for frequent home hemodialysis or acute renal failure was developed at the turn of the 21st century. This system used premanufactured dialysis solution, delivered to the home or dialysis unit, as is done for peritoneal dialysis.     

6-羧基壳聚糖凝胶珠及其吸附尿毒症低分子毒物研究

用NO2将壳聚糖6位羟甲基氧化成羧基,再以戊二醛作交联剂制备了具有较高强度的6羧基壳聚糖凝胶珠。SEM观察确认凝胶珠表面均匀分布许多“沟槽”。凝胶珠对尿毒症低分子毒物尿酸、马尿酸和肌酐的吸附量分别为2.61、1.5和0.81mg/g;几乎不吸附牛血清蛋白、尿素、肌酸。富含低分子毒物的血清经凝胶珠吸附后,其尿酸和马尿酸的含量可接近人体液正常值。     

纳米二氧化钛的发育毒性研究

为了了解纳米TiO2对动物生长发育的影响,取怀孕昆明小鼠在妊娠6～17天内口服纳米TiO2,临产前剖腹产.检测其体重增加、脏器变化、胚胎重量、胚胎体长、胚胎尾长、死胎、畸胎、吸收胎等指标.统计分析显示,该纳米材料对怀孕雌鼠影响不大,但对胚胎却有一定的毒性作用.首次阐述了纳米TiO2具有一定的发育毒性.     

Toxicity studies in a chemical dye production industry in Turkey

This study investigated the acute toxicity of chemical dye production industry wastewaters by traditional and enrichment toxicity tests and emphasized the importance of toxicity tests in wastewater discharge regulations. The enrichment toxicity tests are novel applications indicating whether there is potential toxicity or stimulation conditions. Different organisms were used including bacteria (floc-Zoogloea ramigera and coliform-Escherichia coli bacteria), algae (Chlorella vulgaris), fish (lepistes-Poecilia reticulate) and protozoan (Vorticella campanula) to represent four tropic levels. The toxicity test results were compared with chemical analyses to identify the pollutants responsible for the toxicity in the effluent wastewater samples. Toxicity of the effluents could not be explained by using physicochemical analyses in four cases. The results clearly showed that the use of bioassay tests produce additional information about the toxicity potential of industrial discharges and effluents.     

纳米材料毒性和安全性研究进展

纳米材料的毒性效应研究是纳米技术的一门重要学科,主要研究纳米物质和生物体及环境的相互作用,着重研究纳米物质的物理化学特性等与生物学毒性效应之间的关系。分析了纳米材料毒性研究的特点及产生的背景,以及纳米材料的暴露途径和对生物体及环境的潜在威胁;探讨了纳米材料产生毒性效应的几种可能机制;介绍了国内外几种典型的纳米材料毒性研究情况;展望了今后研究中需重点解决的问题,如加强分子水平上纳米材料毒性效应的研究、构建预测纳米材料潜在影响的理论模型等。     

壳聚糖包裹CdTe的物理表征及生物毒性研究

选用天然多糖中唯一的碱性多糖-壳聚糖作为稳定剂和包裹剂,成功地在水相中以温和条件合成了粒径小小于10nm的壳聚糖包裹cdTe纳米粒子（CdTe／CS）和壳聚糖微球包裹的CdTe纳米粒子（CdTel／CSMs）,对两种纳米粒子物理表征显示,二者均具有较好的光学性质稳定、发射峰峰位分布范围宽、紫外吸收光谱宽且连续的特点。相比ECdTe的毒性,CdTe／CS和cdTe,CsMs纳米粒子的细胞毒性有明显降低,且生物相容性强,可以应用在生物医学检验、细胞成像,甚至活体研究中。     

交联壳聚糖吸附剂对多肽的吸附性能

为了研究血液灌流用多肽吸附剂以治疗尿毒症,本文以戊二醛为交联剂,用反向悬浮聚合方法制备了交联壳聚糖吸附剂,继而用NaBH4还原处理,并对其还原效果和溶胀性能作了表征.吸附实验结果表明,吸附剂对选取的六种多肽均有不同程度的吸附;随着多肽链的增长,吸附剂对其的吸附能力体现出先增强后减小的趋势;对分子量为1 100的垂体后叶素吸附效果最好.同时,吸附动力学曲线表明,随着肽分子量的增大,达到吸附平衡的时间也延长,对六种肽的吸附分别在0.6～2 h内达到平衡.     

量子点的毒性研究进展

量子点是由Ⅱ-Ⅵ族、Ⅳ-Ⅵ族或Ⅲ-Ⅴ族元素构成的半导体纳米晶体.由于量子点具有很强的光电发射效应和光稳定性,被广泛应用于生物医学领域,介绍了量子点在医学检测、药物研究、医学成像、生物芯片及溶液矩阵等方面的应用.阐述了量子点的毒性机理,总结了量子点理化性质和环境因素对量子点毒性的影响.     

In vivo Quantum‐Dot Toxicity Assessment

Quantum dots have potential in biomedical applications, but concerns persist about their safety. Most toxicology data is derived from in vitro studies and may not reflect in vivo responses. Here, an initial systematic animal toxicity study of CdSe–ZnS core–shell quantum dots in healthy Sprague–Dawley rats is presented. Biodistribution, animal survival, animal mass, hematology, clinical biochemistry, and organ histology are characterized at different concentrations (2.5–15.0 nmol) over short‐term (<7 days) and long‐term (>80 days) periods. The results show that the quantum dot formulations do not cause appreciable toxicity even after their breakdown in vivo over time. To generalize the toxicity of quantum dots in vivo, further investigations are still required. Some of these investigations include the evaluation of quantum dot composition (e.g., PbS versus CdS), surface chemistry (e.g., functionalization with amines versus carboxylic acids), size (e.g., 2 versus 6 nm), and shape (e.g., spheres versus rods), as well as the effect of contaminants and their byproducts on biodistribution behavior and toxicity. Combining the results from all of these studies will eventually lead to a conclusion regarding the issue of quantum dot toxicity.     

Toxicity of Metal Oxide Nanoparticles: Mechanisms,Characterization, and Avoiding Experimental Artefacts

Metal oxide nanomaterials are widely used in practical applications and represent a class of nanomaterials with the highest global annual production. Many of those, such as TiO₂ and ZnO, are generally considered non‐toxic due to the lack of toxicity of the bulk material. However, these materials typically exhibit toxicity to bacteria and fungi, and there have been emerging concerns about their ecotoxicity effects. The understanding of the toxicity mechanisms is incomplete, with different studies often reporting contradictory results. The relationship between the material properties and toxicity appears to be complex and diifficult to understand, which is partly due to incomplete characterization of the nanomaterial, and possibly due to experimental artefacts in the characterization of the nanomaterial and/or its interactions with living organisms. This review discusses the comprehensive characterization of metal oxide nanomaterials and the mechanisms of their toxicity.     

An Overview of Reverse Logistics

Until recently, investment in logistics has focused mainly on the flows from companies to markets. Growing concerns for the environment and conserving resources have created new logistical approaches to more effectively manage the distribution function, and make better use of the resources available to an organization. One such approach is reverse logistics, which uses various methods to give scope for a back-load of finished products, components, waste, reusable packing, etc. from consumer to manufacturer. Back-loads allow manufacturers to reduce costs by using the distribution vehicle‘s return journey to create income or added value. This basic concept is now being developed to create novel solutions to the problems of reducing pollution, costs and vehicle movements, whilst maintaining high customer service levels. In this paper, the idea of reverse logistics is presented; motivations for it are analyzed, several successful practices are demonstrated and some important truths regarding successful reverse logistics are identified, trend of reverse logistics is provided.     

纳米吸波材料的研究进展

介绍了纳米吸波材料的吸波原理。叙述了碳纳米管、纳米金属与合金、纳米陶瓷、纳米氧化物、纳米导电高分子几类吸波材料的特点和应用情况。比较了各种吸波材料的优缺点,对吸波材料的研究前景进行了展望。