Murine Model for Contact Sensitization

A method combining murine ear swelling and lymph node cell proliferation was evaluated as a quantitative measurement of delayed-contact sensitization. The method involves one and/or four occluded, abdominal induction applications; use of pertussis toxin as an adjuvant; topical challenge to the ear; baseline and postchallenge ear measurements; and measurement of ¹²⁵I incorporation in axillary lymph nodes after injection of 5-[¹²⁵I]iodo-2'-deoxyuridine ([¹²⁵I]UdR). The inclusion of vehicle-induced/test chemical-challenged control groups permits objective recognition of positive responses by statistical analysis. This model—intended for use in screening for the sensitization potential of topical therapeutics—was evaluated with the known sensitizers tetracaine, naloxone, and oxazolone and with the irritant sodium dodecyl sulfate. Axillary lymph node cell proliferation measured by ¹²⁵I incorporation was a more sensitive measurement of contact sensitization than ear swelling. It was essential to perform both one and four inductions because tetracaine gave the greatest lymph node response after one induction, whereas naloxone produced a sensitization response only after four inductions. Ear swelling response to tetracaine increased after four inductions; however, ear swelling response was not observed after either one or four inductions of naloxone. After one or four inductions of the strong sensitizer, oxazolone, lymph node and ear swelling responses were observed. As expected, no significant ear swelling or lymph node response to sodium dodecyl sulfate was observed after one or four inductions. This method allows quantitative evaluation of contact sensitization by two separate measurements, thereby increasing the potential of identifying sensitizers missed by other methods.     

接触式激光刀在神经外科手术中的应用

随着激光技术的发展,已由之前的非接触式激光刀跳跃至现在的接触式激光刀,它克服了前者的种种限制,使得接触式激光刀更适用于临床,尤其是在神经外科领域,接触式激光刀在神经外科运用范围甚广,本文将对接触式激光刀原理、在神经外科手术中的运用、目前存在的不足及展望,进行逐一阐明,作如下综述。     

MIPPO结合NCB万向锁定板在老年股骨转子间骨折的运用

目的探讨运用MIPPO(微侵入钢板插入技术)结合NCB万向锁定板在老年股骨转子间骨折的治疗效果。方法运用MIPPO结合NCB万向锁定板对2013年7月至2015年10月收治的35例老年转子间骨折患者进行治疗,男21例,女14例;右髖16例,左髖19例;年龄为68~92岁,平均年龄83.5岁,Evans分型Ⅰ型2例,Ⅱ型5例,Ⅲ型11例,Ⅳ型10例,Ⅴ型7例。术前对患者均行骨盆正蛙位X光片和CT扫描,记录患者的手术时间、术中出血量、并发症情况、骨折愈合时间及末次随访时髖关节Harris评分等,初步分析该方法治疗老年股骨转子间骨折疗效和经验。结果本组患者手术时间平均为50.2 min(40~65 min),术中出血量平均为180 m L(150~230 m L)。35例患者术后均获得平均15.6个月(12~39个月)随访,1例出现术后内固定松脱后再行半髖置换治疗,34例术后均获得骨性愈合,平均愈合时间7.8个月(6~9个月)。术后末次随访时34例患者髖关节Harris评分平均为84.5分(75~90分)。结论 MIPPO结合NCB万向锁定板对于老年股骨转子间骨折治疗是有效、可靠的治疗方法,特别对于骨质疏松型股骨转子间骨折,微创MIPPO结合NCB万向锁定板可以达到更好的复位和早期稳定,是对老年股骨转子间骨折微创治疗方法的有益探索。     

Antibody mediated CDCP1 degradation as mode of action for cancer targeted therapy

CUB-domain-containing-protein-1 (CDCP1) is an integral membrane protein whose expression is up-regulated in various cancer types. Although high CDCP1 expression has been correlated with poor prognosis in lung, breast, pancreas, and renal cancer, its functional role in tumor formation or progression is incompletely understood. So far it has remained unclear, whether CDCP1 is a useful target for antibody therapy of cancer and what could be a desired mode of action for a therapeutically useful antibody. To shed light on these questions, we have investigated the cellular effects of a therapeutic antibody candidate (RG7287). In focus formation assays, prolonged RG7287 treatment prevented the loss of contact inhibition caused by co-transformation of NIH3T3 cells with CDCP1 and Src. In a xenograft study, MCF7 cells stably overexpressing CDCP1 reached the predefined tumor volume faster than the parental MCF7 cells lacking endogenous CDCP1. This tumor growth advantage was abolished by RG7287 treatment. In vitro, RG7287 induced rapid tyrosine phosphorylation of CDCP1 by Src, which was accompanied by translocation of CDCP1 to a Triton X-100 insoluble fraction of the plasma membrane. Triggering these effects required bivalency of the antibody suggesting that it involves CDCP1 dimerization or clustering. However, this initial activation of CDCP1 was only transient and prolonged RG7287 treatment induced internalization and down-regulation of CDCP1 in different cancer cell lines. Antibody stimulated CDCP1 degradation required Src activity and was proteasome dependent. Also in three different xenograft models with endogenous CDCP1 expression RG7287 treatment resulted in significant tumor growth inhibition concomitant with substantially reduced CDCP1 levels as judged by immunohistochemistry and Western blotting. Thus, despite transiently activating CDCP1 signaling, the RG7287 antibody has a therapeutically useful mode of action.     

Halos y lentes intraoculares multifocales: origen e interpretación

ObjectiveTo present the theoretical and experimental characterization of the halo in multifocal intraocular lenses (MIOL).MethodThe origin of the halo in a MIOL is the overlaying of 2 or more images. Using geometrical optics, it can be demonstrated that the diameter of each halo depends on the addition of the lens (ΔP), the base power (P^d), and the diameter of the IOL that contributes to the «non-focused» focus. In the image plane that corresponds to the distance focus, the halo diameter (δH^d) is given by: δH^d = d^pn ΔP/P^d, where d^pn is the diameter of the IOL that contributes to the near focus. Analogously, in the near image plane the halo diameter (δHⁿ) is: δHⁿ = d^pd ΔP/P^d, where d^pd is the diameter of the IOL that contributes to the distance focus. Patients perceive halos when they see bright objects over a relatively dark background. In vitro, the halo can be characterized by analyzing the intensity profile of the image of a pinhole that is focused by each of the foci of a MIOL.Results and conclusionsA comparison has been made between the halos induced by different MIOL of the same base power (20D) in an optical bench. As predicted by theory, the larger the addition of the MIOL, the larger the halo diameter. For large pupils and with MIOL with similar aspheric designs and addition (SN6AD3 vs ZMA00), the apodized MIOL has a smaller halo diameter than a non-apodized one in distance vision, while in near vision the size is very similar, but the relative intensity is higher in the apodized MIOL. When comparing lenses with the same diffractive design, but with different spherical-aspheric base design (SN60D3 vs SN6AD3), the halo in distance vision of the spherical MIOL is larger, while in near vision the spherical IOL induces a smaller halo, but with higher intensity due to the spherical aberration of the distance focus in the near image. In the case of a trifocal-diffractive IOL (AT LISA 839MP) the most noticeable characteristic is the double-halo formation due to the 2 non-focused powers.