BACKGROUND & AIMS: BACKGROUND:Chronic osteoarthritis can result in glenohumeral subluxation and loss of posterior glenoid bone. This can alter normal glenohumeral biomechanics and affect the stress placed on the glenoid implant after total shoulder arthroplasty. This study evaluated the clinical and radiographic results of an augmented all-polyethylene glenoid for the treatment of glenoid osteoarthritis in the presence of posterior glenoid bone loss and determined whether any failures or complications occurred with short-term follow-up. METHODS:During a 2-year period, 21 patients were treated with an augmented glenoid for an index diagnosis of osteoarthritis with a biconcave glenoid and average posterior glenoid bone loss of 4.7 mm. Clinical outcomes were recorded for the American Shoulder and Elbow Surgeons Shoulder Assessment, Simple Shoulder Test, and active motion. Radiographic analysis included glenoid version, humeral head subluxation, component seating, ingrowth, and loosening. RESULTS:Significant improvements were demonstrated for American Shoulder and Elbow Surgeons Shoulder Assessment (52.3), Simple Shoulder Test (8.1), forward flexion (50°), external rotation (32°), and pain. Radiographic improvements were found for glenoid version (12°), humeral scapular alignment (23%), and humeral glenoid alignment (8%). Central peg ingrowth was demonstrated in all patients, and complete component seating was achieved in 19 patients. No complications were encountered, and no clinical or radiographic failures were identified. CONCLUSION:Augmented polyethylene glenoid components demonstrated improved clinical outcome, without implant failure or complications, during short-term follow-up.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:To investigate the relation between male infertility and occupational exposures, particularly glycol ethers. METHODS:A case-referent study was designed in which men attending 14 fertility clinics in 11 centres across the UK in 1999-2002 were recruited following 12 months of unprotected intercourse and without a previous semen analysis. Cases were those with low motile sperm concentration (MSC) relative to the time since their last ejaculation (MSC <12 x 10(6) for 3 days of abstinence). Referents were other men attending these clinics and meeting the inclusion criteria. A single semen sample was collected at the clinic and analysed at the andrology laboratory serving each hospital. Concentration was determined manually with motility assessed centrally from video recordings. Exposures and confounding factors were assessed from self-completed and nurse-interviewer questionnaires, completed prior to the results of the semen analysis. The occupational histories were assessed for exposures relative to UK norms by a team of occupational hygienists blind to case status. RESULTS:Of 2118 men in employment at the time of the interview, 874 (41.3%) were cases. Work with organic solvents, particularly glycol ethers, in the 3 months before the first clinic visit was associated with the likelihood of low motile sperm count. Unadjusted odds ratios (OR) for moderate and high glycol ether exposure (compared with none) were 1.70 (95% CI: 1.11 to 2.61) and 2.54 (95% CI: 1.24 to 5.21). Adjustment for potential confounders (surgery to the testes, previous conception, wearing boxer shorts, drinking alcohol, employed in manual work) reduced the risk associated with glycol ether exposure: moderate OR = 1.46 (95% CI: 0.93 to 2.28), high OR = 2.25 (95% CI: 1.08 to 4.69). No other occupational risk factor was identified. CONCLUSIONS:Glycol ether exposure was related to low motile sperm count in men attending fertility clinics. This suggests that, at the time of the study, glycol ethers continued to be a hazard for male fertility.

背景与目标：

BACKGROUND & AIMS: :The effect of propylene glycol (PG) on transdermal flux under current was investigated using conventional in vitro iontophoresis methodology. The results were evaluated to explain how PG affects the electroosmotic volume flow (EVF) and electromigrational flux through skin. As a marker molecule for the direction and magnitude of EVF, a non-charged neutral molecule, acetaminophen (AAP), was used. At pH 7.4, the direction of EVF was from anode to cathode. During anodal and cathodal current application, PG decreased AAP flux and this decrease was proportional to the concentration of PG, indicating that the presence of PG in the medium decreased the EVF. This decrease is likely due to the decrease in dielectric constant of the medium and the increases in medium viscosity by the addition of PG. The increase in AAP solubility and the viscosity of the medium by PG may also contribute to the decrease in diffusional flux. The magnitude of EVF was estimated to be about 4.2 μl/cm(2 )h. The effect of PG on the flux of a positively charged drug, donepezil hydrochloride (DH), was further investigated using pH 4.6 phosphate buffer solution. The permselectivity of skin in this solution was also investigated and revealed that the isoelectric point of hairless mouse skin is higher than pH 4.6. Anodal delivery showed much higher flux than cathodal and passive flux, indicating that electromigration is playing the major role for DH flux. As the concentration of PG increased, anodal flux of DH decreased. The main reason for this decrease in electromigration is likely due to the increase in medium viscosity. These results and discussions clearly suggest that the incorporation of frequently used organic cosolvents and penetration enhancers into the iontophoretic formulation should be carefully chosen with a thorough investigation for their effect on flux. Overall, these results provided further mechanistic insights into the role of electroosmosis and electromigration in flux across skin, and how they can be modulated by organic cosolvent, PG.

背景与目标： : 使用常规的体外离子电渗法研究了丙二醇 (PG) 对电流下透皮通量的影响。对结果进行了评估，以解释PG如何影响通过皮肤的电渗体积流量 (EVF) 和电迁移通量。作为EVF方向和大小的标记分子，使用了不带电的中性分子对乙酰氨基酚 (AAP)。在pH 7.4时，EVF的方向是从阳极到阴极。在阳极和阴极电流施加期间，PG降低了AAP通量，并且这种降低与PG的浓度成正比，表明培养基中PG的存在降低了EVF。这种降低可能是由于介质的介电常数降低和通过添加PG而增加介质粘度。PG增加AAP溶解度和介质粘度也可能导致扩散通量的降低。估计EVF的大小约为4.2 μ l/cm(2 )h。使用pH 4.6磷酸盐缓冲溶液进一步研究了PG对带正电的药物盐酸多奈哌齐 (DH) 的通量的影响。还研究了该溶液中皮肤的渗透选择性，并发现无毛小鼠皮肤的等电点高于pH 4.6。阳极递送显示出比阴极和被动通量高得多的通量，表明电迁移在DH通量中起主要作用。随着PG浓度的增加，DH的阳极通量降低。电迁移减少的主要原因可能是由于介质粘度的增加。这些结果和讨论清楚地表明，应仔细选择将常用的有机助溶剂和渗透增强剂掺入离子电渗制剂中，并仔细研究其对通量的影响。总体而言，这些结果为电渗和电迁移在整个皮肤通量中的作用以及如何通过有机助溶剂PG调节它们提供了进一步的机械见解。

BACKGROUND & AIMS: :Background and purpose - Most registry studies regarding highly crosslinked polyethylene (XLPE) have focused on the overall revision risk. We compared the risk of cup and/or liner revision for specific cup and liner designs made of either XLPE or conventional polyethylene (CPE), regarding revision for any reason and revision due to aseptic loosening and/or osteolysis. Patients and methods - Using the Nordic Arthroplasty Register Association (NARA) database, we identified cup and liner designs where either XLPE or CPE had been used in more than 500 THAs performed for primary hip osteoarthritis. We assessed risk of revision for any reason and for aseptic loosening using Cox regression adjusted for age, sex, femoral head material and size, surgical approach, stem fixation, and presence of hydroxyapatite coating (uncemented cups). Results - The CPE version of the ZCA cup had a risk of revision for any reason similar to that of the XLPE version (p = 0.09), but showed a 6-fold higher risk of revision for aseptic loosening (p < 0.001). The CPE version of the Reflection All Poly cup had an 8-fold elevated risk of revision for any reason (p < 0.001) and a 5-fold increased risk of revision for aseptic loosening (p < 0.001). The Charnley Elite Ogee/Marathon cup and the Trilogy cup did not show such differences. Interpretation - Whether XLPE has any advantage over CPE regarding revision risk may depend on the properties of the polyethylene materials being compared, as well as the respective cup designs, fixation type, and follow-up times. Further research is needed to elucidate how cup design factors interact with polyethylene type to affect the risk of revision.

背景与目标： 背景和目的-大多数关于高度交联聚乙烯 (XLPE) 的注册研究都集中在整体修订风险上。我们比较了由XLPE或常规聚乙烯 (CPE) 制成的特定杯子和衬里设计的杯子和/或衬里修订的风险，关于任何原因的修订和由于无菌性松动和/或骨溶解引起的修订。患者和方法-使用北欧关节置换术协会 (NARA) 数据库，我们确定了cup和liner设计，其中XLPE或CPE已用于500多个用于原发性髋关节骨关节炎的tha。我们使用Cox回归对年龄，性别，股骨头材料和大小，手术方法，茎固定和羟基磷灰石涂层 (未骨水泥杯) 的存在进行校正，评估了因任何原因进行翻修和无菌性松动的风险。结果-ZCA cup的CPE版本由于与XLPE版本相似的任何原因而具有修订风险 (p = 0.09)，但显示出无菌松动的修订风险高6倍 (p <0.001)。反射全聚杯的CPE版本由于任何原因而具有8倍的修正风险 (p < 0.001) 和5倍的无菌性松动的修正风险 (p <0.001)。Charnley Elite Ogee/马拉松杯和Trilogy杯没有显示出这种差异。解释-XLPE在修订风险方面是否比CPE具有任何优势可能取决于所比较的聚乙烯材料的特性，以及相应的杯子设计，固定类型和后续时间。需要进一步的研究来阐明杯子设计因素如何与聚乙烯类型相互作用以影响修订风险。

BACKGROUND & AIMS: :Theranostic nanoparticles can deliver therapeutic agents as well as diverse imaging agents to tumors. The enhanced permeation and retention (EPR) effect is regarded as a crucial mechanism for the tumor-targeted delivery of nanoparticles. Although a large number of studies of the EPR effect of theranostic nanoparticles have been performed, the effect of the change in the body size of the host on the EPR effect is not fully understood. In this regard, comparative research is needed on the behavior of nanoparticles in large animals for developing the nanoparticles to the clinical stage. In this study, we prepared fluorophore (indocyanine green (ICG) or cyanine 5.5 (Cy5.5))-conjugated glycol chitosan nanoparticles (CNPs) for comparing the tumor-targeting efficacy in VX2 tumor-bearing mouse and rabbit models. As expected, the CNPs formed nano-sized spherical nanoparticles and were stable for 8 days under aqueous conditions. The CNPs also exhibited dose-dependent cellular uptake into VX2 tumor cells without cytotoxicity. The half-life of the near-infrared fluorescence (NIRF) signals in the blood were 3.25 h and 4.73 h when the CNPs were injected into mice and rabbits, respectively. Importantly, the CNPs showed excellent tumor accumulation and prolonged biodistribution profiles in both the VX2 tumor-bearing mouse and rabbit models, wherein the tumor accumulation was maximized at 48 h and 72 h, respectively. Based on the excellent tumor accumulation of the CNPs, finally, the CNPs were used in the image-guided surgery of the rabbit orthotopic VX2 lung tumor model. The lung tumor tissue was successfully removed based on the NIRF signal from the CNPs in the tumor tissue. This study shows that CNPs can be potentially used for tumor theragnosis in small animals and large animals.

背景与目标： : 肿瘤纳米颗粒可以向肿瘤输送治疗剂和多种成像剂。增强的渗透和保留 (EPR) 效应被认为是纳米颗粒靶向肿瘤递送的关键机制。尽管已经对theranostic纳米颗粒的EPR效应进行了大量研究，但尚未完全了解宿主体尺寸的变化对EPR效应的影响。在这方面，需要对纳米颗粒在大型动物中的行为进行比较研究，以将纳米颗粒发展到临床阶段。在这项研究中，我们制备了荧光团 (吲哚菁绿 (ICG) 或花青5.5 (Cy5.5))-共轭乙二醇壳聚糖纳米颗粒 (CNPs)，用于比较VX2荷瘤小鼠和兔模型中的肿瘤靶向功效。如预期的那样，CNPs形成了纳米级的球形纳米颗粒，并且在水性条件下稳定了8天。CNPs还表现出剂量依赖性细胞摄取到VX2肿瘤细胞中，而没有细胞毒性。当将cnp注射到小鼠和兔子中时，血液中近红外荧光 (NIRF) 信号的半衰期分别为3.25 h和4.73 h。重要的是，CNPs在VX2荷瘤小鼠和兔模型中均显示出出色的肿瘤积累和延长的生物分布曲线，其中肿瘤积累分别在48小时和72小时达到最大。基于CNPs的优良肿瘤积累，最后将CNPs用于兔原位VX2肺肿瘤模型的图像引导手术中。根据肿瘤组织中CNPs的NIRF信号成功切除了肺肿瘤组织。这项研究表明，CNPs可以潜在地用于小动物和大动物的肿瘤治疗。

BACKGROUND & AIMS: :The benefits of bowel preparation prior to capsule endoscopy (CE) are controversial. The aim of this study was to examine whether ingesting a small amount of polyethylene glycol (PEG) during, not before, the CE procedure improves the image quality and the cecal completion rate. A prospective single-blind controlled study was conducted including 59 patients. The initial 32 patients (group A) received no preparation, and the subsequent 27 patients (group B) ingested 500 ml of PEG starting 30 min after swallowing the capsule. The capsule reached the cecum in 65.6% of the patients in group A and 88.9% of the patients in group B (P = 0.038). The use of PEG during CE examination significantly improved the image quality, and this effect was more pronounced in the distal ileum. Ingesting a small amount of PEG during CE examination significantly improves both the CE image quality and the cecal completion rate.

背景与目标： : 胶囊内窥镜检查 (CE) 之前肠道准备的好处是有争议的。这项研究的目的是检查在CE过程中 (而不是在CE过程之前) 摄入少量聚乙二醇 (PEG) 是否可以改善图像质量和盲肠完成率。进行了一项前瞻性单盲对照研究，包括59名患者。最初的32名患者 (A组) 未接受任何准备，随后的27名患者 (B组) 在吞咽胶囊30分钟后开始摄入500毫升PEG。胶囊到达盲肠A组患者的65.6% 和B组患者的88.9% (P = 0.038)。在CE检查过程中使用PEG可显着提高图像质量，并且这种效果在回肠远端更为明显。在CE检查过程中摄入少量PEG可显着提高CE图像质量和盲肠完成率。

BACKGROUND & AIMS: :A revision (C35r) to the CHARMM ether force field is shown to reproduce experimentally observed conformational populations of dimethoxyethane. Molecular dynamics simulations of 9, 18, 27, and 36-mers of polyethylene oxide (PEO) and 27-mers of polyethylene glycol (PEG) in water based on C35r yield a persistence length lambda = 3.7 A, in quantitative agreement with experimentally obtained values of 3.7 A for PEO and 3.8 A for PEG; agreement with experimental values for hydrodynamic radii of comparably sized PEG is also excellent. The exponent upsilon relating the radius of gyration and molecular weight (R(g) proportional, variantM(w)(upsilon)) of PEO from the simulations equals 0.515 +/- 0.023, consistent with experimental observations that low molecular weight PEG behaves as an ideal chain. The shape anisotropy of hydrated PEO is 2.59:1.44:1.00. The dimension of the middle length for each of the polymers nearly equals the hydrodynamic radius R(h)obtained from diffusion measurements in solution. This explains the correspondence of R(h) and R(p), the pore radius of membrane channels: a polymer such as PEG diffuses with its long axis parallel to the membrane channel, and passes through the channel without substantial distortion.

背景与目标： : 对CHARMM醚力场的修订 (C35r) 显示为重现实验观察到的二甲氧基乙烷构象种群。基于C35r的水中9、18、27和36聚环氧乙烷 (PEO) 和27聚乙二醇 (PEG) 的分子动力学模拟产生的持续长度 λ = 3.7 a，与实验获得的PEO的3.7 A和PEG的3.8 A的数值定量一致; 与相当大小的PEG的流体动力半径的实验值的一致性也很好。来自模拟的PEO的旋转半径和分子量 (R(g) 比例，变量m (w)(upsilon)) 相关的指数upsilon等于0.515/- 0.023，与低分子量PEG表现为理想链的实验观察结果一致。水合PEO的形状各向异性为2.59:1.44:1.00。每种聚合物的中间长度尺寸几乎等于从溶液中的扩散测量获得的流体动力半径R(h)。这解释了R(h) 和R(p) 的对应关系，即膜通道的孔半径: 诸如PEG之类的聚合物以其长轴平行于膜通道的方式扩散，并通过该通道而不会产生实质性变形。

BACKGROUND & AIMS: :Renal cortical slices were treated with 2.1 M cryoprotectant in RPS-2 vehicle solution, cooled at one of four rates to -40 degrees C, then immediately warmed at one of four rates to 25 degrees C for determination of the [K+]/[Na+] after a standard incubation period. Results are presented in the form of survival "topographical maps" or surfaces with the x axis representing [K+]/[Na+]; the y axis, cooling rate; and the z axis, warming rate. The rate of temperature change fell in the range of 0.5 to 10 degrees C/min. The results suggest that when RPS-2 vehicle solution is used for 2.1 M cryoprotectants, Me2SO offers the prospect for greatest post-thaw recovery. With this vehicle-cryoprotective agent combination, the greatest post-thaw recovery is attained with cooling-warming combinations of -3, +4, and -0.5, +10 degrees C/min.

背景与目标： : 肾皮质切片用2.1 M冷冻保护剂在RPS-2赋形溶液中处理，以四种速率之一冷却至-40 ℃，然后立即以四种速率之一加热至25 ℃，以在标准孵育期后测定 [K +]/[Na +]。结果以生存 “地形图” 或x轴表示 [K]/[Na] 的曲面的形式呈现; Y轴，冷却速率; 和z轴，升温速率。温度变化率在0.5 ~ 10 ℃/min范围内下降。结果表明，当RPS-2载体溶液用于2.1 M冷冻保护剂时，Me2SO为最大的解冻后恢复提供了前景。使用这种载体-冷冻保护剂组合，用-3、 + 4和-0.5、 + 10 ℃/min的冷却-加热组合获得最大的解冻后恢复。

BACKGROUND & AIMS: :Constipation is a common and chronic problem in children worldwide. Long-term use of laxatives is necessary for successful treatment of chronic constipation. Commonly used laxatives in children include milk of magnesia, lactulose, mineral oil, and polyethylene glycol (PEG). Recent studies report the efficacy and safety of PEG for the long-term treatment of constipation in children. Because of its excellent patient acceptance, PEG is being used widely in children for constipation. In this commentary, we review the recently published pediatric literature on the efficacy, safety, and patient acceptance of PEG. We also assess the role of PEG in childhood constipation by comparing it with other laxatives in terms of efficacy, safety, patient acceptance, and cost.

背景与目标： : 便秘是全世界儿童的常见和慢性问题。长期使用泻药对于成功治疗慢性便秘是必要的。儿童常用的泻药包括氧化镁，乳果糖，矿物油和聚乙二醇 (PEG) 的牛奶。最近的研究报告了PEG长期治疗儿童便秘的疗效和安全性。由于其出色的患者接受度，PEG已广泛用于儿童便秘。在这篇评论中，我们回顾了最近发表的有关PEG的疗效，安全性和患者接受度的儿科文献。我们还通过将PEG与其他泻药在功效，安全性，患者接受度和成本方面进行比较，评估了PEG在儿童便秘中的作用。

BACKGROUND & AIMS: :Poly(ethylene glycol) (PEG) is a versatile biocompatible polymer. Improvement of its limited functionality (two chain termini) may significantly expand its current applications. In this communication, a simple and yet highly efficient strategy for the synthesis of linear multifunctional PEGs with "click" chemistry is reported. A short acetylene-terminated PEG was linked by 2,2-bis(azidomethyl)propane-1,3-diol using Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition in water at room temperature. High-molecular-weight PEGs with pendant hydroxyl groups were obtained and characterized by 1H NMR and size-exclusion chromatography. A prototype bone-targeting polymeric drug delivery system was also successfully synthesized based on this new method. It demonstrates strong biomineral-binding ability and the ease of incorporating therapeutic agents into the delivery system. This simple "click" reaction approach provides a useful tool for the development of novel functional polymers and their conjugates for biomedical applications.

背景与目标： : 聚乙二醇 (PEG) 是一种多功能的生物相容性聚合物。改善其有限的功能 (两个链末端) 可能会大大扩展其当前的应用。在此通讯中，报告了一种简单而高效的策略，用于合成具有 “点击” 化学作用的线性多功能钉。在室温下，使用Cu(I) 催化的Huisgen 1,3-偶极环加成反应，通过2,2-双 (叠氮甲基) 丙烷-1,3-二醇在水中连接短的乙炔封端的PEG。获得了具有侧基羟基的高分子量peg，并通过1H NMR和尺寸排阻色谱进行了表征。基于这种新方法，还成功地合成了原型骨靶向聚合物药物递送系统。它具有很强的生物结合能力，并且易于将治疗剂掺入给药系统。这种简单的 “点击” 反应方法为开发用于生物医学应用的新型功能性聚合物及其缀合物提供了有用的工具。

BACKGROUND & AIMS: The mechanistic and morphological origins of microscopic wear debris generated from UHMWPE articular surfaces in total joint replacement prostheses are investigated in this study. It was found experimentally that the molecular chain structure at the articulating surface of UHMWPE undergoes a re-organization process due to strain accumulation caused by surface traction. This molecular re-organization process creates a fibre-like surface texture that exhibits an anisotropic behaviour similar to a unidirectionally reinforced polymer composite. This composite responds to stresses favourably if loaded along the fibre axis but unfavourably if loaded off axis. Due to the very complex multi-axial motion/loading nature at the articular surfaces in total joint replacements, the stress tensors applied to each localized asperity contact area continuously change their directions and magnitudes. These changes in the localized stress field create an off-axis loading situation at each localized contact zone with respect to the orientation of the molecular chains. Depending on the off-axis angle, failure of the molecular structure occurs in three different waystensile rupture at very small off-axis angles, shear rupture at intermediate off-axis angles and transverse splitting at large off-axis angles. These failure mechanisms all produce similar fibre-like wear debris. However, the failure stresses differ significantly among the three modes. According to this molecular wear theory, the preferred polymer microstructure for optimal wear resistance would be a three-dimensionally strong network connected by covalent bonds between molecular chains. For UHMWPE, a three-dimensional molecular network can be created by radiation induced cross-linking. Experiments conducted on both gamma irradiated and unirradiated UHMWPE specimens using a linear wear machine and multi-axial joint simulators confirmed the validity of the molecular wear theory.

背景与目标： 在这项研究中，研究了全关节置换假体中UHMWPE关节表面产生的微观磨损碎片的机理和形态来源。实验发现，由于表面牵引力引起的应变积累，UHMWPE关节表面的分子链结构经历了重组过程。这种分子重组过程会产生类似纤维的表面纹理，该纹理表现出类似于单向增强聚合物复合材料的各向异性行为。如果沿纤维轴加载，该复合材料对应力的响应良好，但如果偏离轴加载，则对应力的响应不利。由于全关节置换中关节表面的多轴运动/载荷性质非常复杂，因此施加到每个局部凹凸接触区域的应力张量会不断改变其方向和大小。相对于分子链的方向，局部应力场的这些变化在每个局部接触区产生了离轴载荷情况。根据离轴角的不同，分子结构的破坏发生在三种不同的离轴角下，在非常小的离轴角下发生断裂，在中间离轴角下发生剪切断裂，在大的离轴角下发生横向分裂。这些失效机制都会产生类似纤维的磨损碎片。但是，三种模式之间的失效应力差异很大。根据该分子磨损理论，最佳耐磨性的优选聚合物微观结构将是通过分子链之间的共价键连接的三维强网络。对于UHMWPE，可以通过辐射诱导的交联创建三维分子网络。使用线性耐磨机和多轴关节模拟器对伽马辐照和未辐照的UHMWPE样品进行的实验证实了分子磨损理论的有效性。

BACKGROUND & AIMS: BACKGROUND:Crossfire cross-linked polyethylene is produced differently from other cross-linked polyethylene materials; a below-melt-temperature annealing process is used with the goal of avoiding compromised mechanical properties. The present study was performed to evaluate retrieved Crossfire acetabular cups to determine whether they had oxidized and to what extent oxidation might have influenced their clinical performance. METHODS:Eleven acetabular cups were received at retrieval and a twelfth acetabular cup was received two years post-retrieval over a period of four years. None were retrieved because of polyethylene wear or fatigue. The cups had been in vivo from 0.1 to 5.3 years. Each was examined visually, clinical fatigue damage was rated, and oxidation was measured with use of Fourier transform infrared spectroscopy. RESULTS:The cups exhibited oxidation that varied with its location on the cup: the oxidation value was generally low on the articular surface but more than an order of magnitude higher value on the rim. Maximum rim oxidation correlated significantly with the time in vivo (Spearman rho = 0.734, p = 0.010). Oxidation was identified visually by a white band in thin sections on the rim of seven of the cups and on the articular surface of one of these seven cups. Six of the seven cups also exhibited clinical fatigue damage. Eight of the twelve cups exhibited evidence of impingement or dislocation. CONCLUSIONS:Acetabular cups made of Crossfire polyethylene oxidized to a measurable degree. The oxidation-related reduction of polyethylene mechanical properties was sufficient to allow the fatigue damage seen in these retrieved cups.

背景与目标：

BACKGROUND & AIMS: :Several methods for the preparation of sterically stabilized immunoliposomes (SIL) have recently been described. This report examines an established method for coupling anti-CD34 My10 mAb to poly(ethylene glycol)-liposomes (PEG-liposomes) containing the anchor pyridyldithiopropionylamino-PEG-phosphatidylethanolamine (PDP-PEG-PE) via a cleavable disulfide bond. Efficient attachment of pyridyldithio-derivatized mAb took place (equivalent to coupling ca. 70% of total input protein) at 2 mol percent of the functionalized PEG-lipid. The My10-SIL bound specifically to CD34+ cells (human leukemic KG-1a and hematopoietic progenitor cells) and the extent of binding was a function of liposomal lipid concentration, the mAb density in the liposome surface and the CD34 cell expression. In mixtures with CD34- cells (CHO or Jurkat), CD34+KG-1a cells were determined by flow cytometry at percentages (1-4%) similar to those reported in clinical samples (such as cord blood, mobilized peripheral blood and bone marrow) using a direct immunostaining with My10-SIL. The disulfide bond was stable in cell culture medium (10% of fetal calf serum) during 8 h and cell-bound SIL can be released from cells by treatment with dithiothreitol as reducing agent under mild conditions (1 h of incubation with 50 mM DTT at 20 degrees C). SIL binding and subsequent dithiothreitol treatment did not influence the cell viability. Our approach should contribute to the development of targetable liposomal vehicles to CD34+ cells for use in ex vivo conditions as sorting of hematopoietic stem cells.

背景与目标： : 最近已经描述了几种制备空间稳定的免疫脂质体 (SIL) 的方法。本报告研究了一种通过可切割的二硫键将anti-CD34 My10 mAb与含有锚定吡啶基二硫代丙酰氨基-PEG-磷脂酰乙醇胺 (PDP-PEG-PE) 的聚 (乙二醇)-脂质体 (PEG-脂质体) 偶联的方法。在2摩尔 % 的官能化PEG-脂质处发生吡啶基二硫基衍生的mAb的有效附着 (相当于总输入蛋白的约70% 偶联)。My10-SIL与CD34细胞 (人白血病KG-1a和造血祖细胞) 特异性结合，结合程度是脂质体脂质浓度，脂质体表面mAb密度和CD34细胞表达的功能。在与CD34-细胞 (CHO或Jurkat) 的混合物中，通过流式细胞术以与临床样品 (如脐带血、动员的外周血和骨髓) 中报道的相似的百分比 (1-4%) 用My10-SIL直接免疫染色测定CD34 + KG-1a细胞。在8 h期间，二硫键在细胞培养基 (胎牛血清的10%) 中是稳定的，并且可以通过在温和条件下用二硫苏糖醇作为还原剂处理 (在20 ℃ 下与50 mmdtt孵育1小时) 从细胞释放细胞结合的SIL。SIL结合和随后的二硫苏糖醇处理不会影响细胞活力。我们的方法应有助于开发针对CD34细胞的可靶向脂质体载体，以在离体条件下用作造血干细胞的分选。

BACKGROUND & AIMS: Insulin-like growth factor (IGF) binding protein-1 (BP-1) inhibits IGF-mediated proliferation of some breast cancer cell lines in vitro. Here we examined whether recombinant human wild-type IGFBP-1 (WT-BP-1) and IGFBP-1 conjugated with polyethylene glycol (PEG-BP-1) could inhibit breast cancer growth. Three breast cancer cell lines were usedMCF-7, MDA-MB-231 and MDA-MB-435A (ascites model). The cells were grown in agar with or without the BP-1 conjugates to investigate their effect on colony formation. Both WT-BP-1 and PEG-BP-1 inhibited anchorage-independent growth (AIG) of MCF-7 and MDA-MB-435A cells. AIG of MDA-MB-231 cells was not inhibited by PEG-BP-1, whereas WT-BP-1 significantly stimulated colony number. We also tested both forms of BP-1 in xenograft tumour models. Two solid breast tumour models were studied using MCF-7 and MDA-MB-231 cell lines, and one ascites model using the MDA-MB-435A cell line. PEG-BP-1 inhibited malignant ascites formation in the MDA-MB-435A model. Conversely, PEG-BP-1 did not significantly inhibit MCF-7 xenograft growth. However, the MDA-MB-231 tumour growth curves were significantly different by a constant amount, suggesting that PEG-BP-1 treatment inhibited early tumour growth of this cell line. In contrast, WT-BP-1 was ineffective in the MDA-MB-231 tumours. These data show that anti-IGF strategies can be used to inhibit breast cancer cell growth. Since PEG-BP-1 inhibited the in vivo, but not in vitro, growth of MDA-MB-231, we speculate that PEG-BP-1 may block host IGF functions required for optimal tumorigenesis. Because PEG-BP-1 has a prolonged serum half-life compared to WT-BP-1, we conclude that improvements in BP-1 pharmacological properties enhanced its antitumour effects in vivo.

背景与目标： 胰岛素样生长因子 (IGF) 结合蛋白-1 (BP-1) 在体外抑制IGF介导的某些乳腺癌细胞系的增殖。在这里，我们研究了重组人野生型IGFBP-1 (WT-BP-1) 和与聚乙二醇 (PEG-BP-1) 偶联的IGFBP-1是否可以抑制乳腺癌的生长。usedMCF-7，MDA-MB-231和MDA-MB-435A三种乳腺癌细胞系 (腹水模型)。将细胞在具有或不具有BP-1缀合物的琼脂中生长，以研究它们对集落形成的影响。WT-BP-1和PEG-BP-1均抑制MCF-7和MDA-MB-435A细胞的锚定非依赖性生长 (AIG)。MDA-MB-231细胞的AIG不受PEG-BP-1抑制，而WT-BP-1显着刺激了集落数。我们还在异种移植肿瘤模型中测试了两种形式的BP-1。使用MCF-7和MDA-MB-231细胞系研究了两个实体乳腺肿瘤模型，以及使用MDA-MB-435A细胞系研究了一个腹水模型。在MDA-MB-435A模型中，PEG-BP-1抑制了恶性腹水的形成。相反，PEG-BP-1没有显著抑制MCF-7异种移植生长。然而，MDA-MB-231的肿瘤生长曲线以恒定的量显着不同，表明PEG-BP-1治疗抑制了该细胞系的早期肿瘤生长。相反，WT-BP-1在MDA-MB-231肿瘤中无效。这些数据表明，抗IGF策略可用于抑制乳腺癌细胞的生长。由于PEG-BP-1抑制了MDA-MB-231的体内生长，而不是体外生长，因此我们推测PEG-BP-1可能会阻断最佳肿瘤发生所需的宿主IGF功能。由于与WT-BP-1相比，PEG-BP-1的血清半衰期延长，因此我们得出结论，BP-1药理特性的改善增强了其体内抗肿瘤作用。

BACKGROUND & AIMS: :Polyethylene glycol-g-polyvinyl alcohol (PEG-PVA) grafted copolymer was administered by gavage to groups of 25 male and 25 female young Wistar rats at doses of 0 (vehicle control), 100, 300, or 1000 mg/kg bw/day for one generation (F0). The study followed the treated F0 generation through mating, gestation, lactation, and weaning of the F1 generation. F1 animals were mated and followed to gestation day (GD) 15-17 at which time F2 implants were evaluated. There were no indications from the various clinical and gross pathological examinations that the oral administration of PEG-PVA grafted copolymer to the F0-parental rats produced any signs of general, reproductive, or developmental toxicity in the F0 or F1 animals or F2 implants. Based on the lack of any dose-related or biologically relevant effects on fertility, reproduction, development, and overall health of rats gavaged with PEG-PVA grafted copolymer and their progeny, the no-observed-adverse effect level (NOAEL) was determined to be the highest dose tested of 1000 mg/kg bw/day.

背景与目标： 聚乙二醇-g-聚乙烯醇 (peg-pva) 接枝共聚物通过管饲法以0 (载体对照) 、100、300或1000 mg/kg体重/天的剂量给予25只雄性和25只雌性年轻Wistar大鼠的组1代 (F0)。该研究通过F1代的交配，妊娠，哺乳和断奶来跟踪处理过的F0代。与F1动物进行了杂交，并在妊娠15-17日进行了评估，评估了F2植入物。从各种临床和总体病理检查中没有迹象表明，向F0-parental大鼠口服PEG-PVA接枝共聚物会在F0或F1动物或F2植入物中产生任何一般，生殖或发育毒性的迹象。基于对用PEG-PVA接枝共聚物及其后代灌胃的大鼠的生育力，繁殖，发育和整体健康缺乏任何剂量相关或生物学相关的影响，未观察到的不良反应水平 (NOAEL) 被确定为1000 mg/kg bw/天的最高测试剂量。