Kinetic study of glomerular epithelial cells associated with segmental glomerular sclerotic lesions with adhesion in spontaneously diabetic WBN/Kob rats

Background We previously found that glomerular epithelial cells play an important role in the formation of adhesive lesions. Glomerular sclerotic lesions develop after the inital adhesive lesions. Methods Two series of experiments were done with spontaneously diabetic WBN/Kob rats. These rats develop segmental glomerular sclerotic lesions with aging. The first series of experiments was intended to clarify the kinetics of glomerular cells on progressive glomerular damage in these rats. The second series of experiments was designed to study the relationship between proliferation (judged by % bromodeoxyuridine-positive cells) of glomerlar epithelial cells and sclerotic lesions with adhesions. Results In the first series, rats having increased proteinuria showed segmental glomerular sclerotic lesions with adhesions. At the same time, increased labeling indices of tuft cells and epithelial cells of Bowman's capsule were observed. In the second series, no significant increase in the labeling indices of tuft cells with sclerotic lesions was observed, compared to tuft cells without sclerotic lesions. In sclerotic lesions with adhesion, bromodeoxyurdine-positive cells were observed that were not distinguishable as podocytes or epithelial cells of Bowman's capsule. The highest labelling index was noted in the epithelial cells of Bowman's capsules with sclerosis. Conclusion This study shows that the proliferation of glomerular epithelial cells (mainly epithelial cells of Bowman's capsule) occurs in glomerular sclerotic lesions with adhesions.     

Synthesis of 14C‐labeled piperidines and application to synthesis of [14C]SCH 351125, a CCR5 receptor antagonist

1‐Benzyl‐4‐hydroxy[2‐¹⁴C]piperidine, a useful intermediate in labeled compound synthesis, was prepared from [¹⁴C]formaldehyde in high yield. The distribution pattern of ¹⁴C in the product is consistent with a mechanism involving reversible iminium ion formation and rapid equilibration of the iminium ion through a cationic aza‐Cope rearrangement. These steps precede the rate‐determining intramolecular cyclization step. SCH 351125 is a potent, selective CCR5 receptor antagonist with potential as a treatment for HIV infection. [¹⁴C]SCH 351125, required for metabolism studies, was prepared from 1‐benzyl‐4‐hydroxy[2‐¹⁴C]piperidine in six steps. [¹⁴C]SCH 351125 is a mixture of four atropisomers. Preparation of [¹⁴C]SCH 351125 besylate salt of the desired atropisomer pair is also described. Copyright © 2007 John Wiley & Sons, Ltd.     

山东农村儿童膳食中人体锌吸收率的测定

目的:测定山东农村儿童代表性膳食中锌(Zn)的人体吸收率。方法:模拟山东农村典型膳食模式,采用富集的天然低丰度稳定性同位素67Zn标记ZnCl2,使用热电离质谱法(TIMS)检测膳食和粪便中总锌含量与67Zn/68Zn比值,计算锌的真吸收率;使用原子吸收分光光度计穴AAS雪测定膳食与粪便的总锌,计算锌的表观吸收率。同时测定影响锌吸收的因子膳食脂肪、蛋白、植酸、纤维素和维生素C(Vc)的含量,计算日平均摄入量,将其结果与我国儿童每日推荐膳食营养素摄入量(RNIs)进行比较。结果:锌的真吸收率为(12.94±3.32)%,锌的表观吸收率为(22.37±1.59)%,两者差异有统计学意义(P<0.05)。锌的平均日摄入量为11.16mg,占RNI的111.6%,高于推荐量。蛋白质和Vc的日摄入量分别为31.2g与13.3mg,占RNIs的56.73%和29.60%,低于推荐量。脂肪、植酸和膳食纤维的日摄入量较高。结论:在蛋白质和Vc的日摄入量较低,脂肪、植酸和膳食纤维的日摄入量较高的条件下,锌的真吸收率较低。     

Whole-brain 3D perfusion MRI at 3.0 T using CASL with a separate labeling coil.

A variety of continuous and pulsed arterial spin labeling (ASL) perfusion MRI techniques have been demonstrated in recent years. One of the reasons these methods are still not routinely used is the limited extent of the imaging region. Of the ASL methods proposed to date, continuous ASL (CASL) with a separate labeling coil is particularly attractive for whole-brain studies at high fields. This approach can provide an increased signal-to-noise ratio (SNR) in perfusion images because there are no magnetization transfer (MT) effects, and lessen concerns regarding RF power deposition at high field because it uses a local labeling coil. In this work, we demonstrate CASL whole-brain quantitative perfusion imaging at 3.0 T using a combination of strategies: 3D volume acquisition, background tissue signal suppression, and a separate labeling coil. The results show that this approach can be used to acquire perfusion images in all brain regions with good sensitivity. Further, it is shown that the method can be performed safely on humans without exceeding the current RF power deposition limits. The current method can be extended to higher fields, and further improved by the use of multiple receiver coils and parallel imaging techniques to reduce scan time or provide increased resolution.     

Nucleic acid spot hybridization with nonradioactive labeled probes in screening for human papillomavirus DNA sequences

We examined 161 human tissue samples using the spot hybridization technique with nonradioactive labeled DNA probes of human papillomavirus (HPV). Whole cells were spotted on nitrocellulose filters; DNA of the cells was denatured and fixed to the filter. Then the DNA spots were hybridized to nonradioactive labeled DNA and monitored by a sandwich immunoenzymatic reaction. This technique is simple, sensitive, specific, requires no special equipment, and can be used in clinical settings. HPV DNA was found in 92% of samples in which, on the basis of histologic and colposcopic criteria, its presence was suspected, as well as in 31 samples where it was not suspected.     

脊神经节神经元周围突至肾及体壁的分支投射

实验将快蓝(FB)和核黄(NY)分别注入大鼠左肾纤维膜下及左体壁神经干内,结果在荧光镜下发现左T_(9-13),L1脊神经后根节(DRG)内存在双标记细胞,提示大鼠T_(9-13),L1段DRG内的部分神经元的周围突分支支配肾及体壁,为肾绞痛所致牵涉痛的解释,提供了神经解剖学基础。     

管状骨增宽牵引成骨组织形态学变化的实验研究

目的 探讨管状骨增宽牵引后新骨形成的变化。方法 在成年山羊的后肢放置2只增宽牵引器。实验组9只术后第8天牵引，对照组3只不牵引。牵引完毕后不同时期，各宰杀3只，评价管状骨增宽牵引后新骨形成的质和量。结果 实验组胫骨平均增宽7．83mm，X射线见牵引间隙逐渐变模糊，暴露侧有骨不连，非暴露侧成骨良好，牵引完毕3个月，未暴露侧新形成板层骨与原来胫骨融为一体，而暴露侧骨不连区为致密纤维组织。结论 管状骨增宽牵引成骨后，两侧牵引间隙成骨不一致，良好的血供，对新骨形成至关重要。     

Syntheses of radiolabeled ABT‐578 for ADME studies

Several isotopomers of ABT‐578 ( I , II , III , and IV ) were prepared starting from different labeled precursors: [5'‐³H]‐tetrazole ( 1 ), [5'‐¹⁴C]‐tetrazole ( 2 ), [40‐³H]rapamycin ( 3 ), and [2,11,31‐³H]rapamycin ( 4 ). It was shown that the tritium label at the 40 position of rapamycin is lost during an attempted synthesis of [40‐³H]ABT‐578 ( III ). Copyright © 2006 John Wiley & Sons, Ltd.     

99Tcm直接法标记血管抑素

目的: 探索用99Tcm直接标记血管抑素(angiostatin, AS)的方法,并研究标记产物的体外稳定性及其生物活性. 方法:制备的AS经鉴定后,分别用2-巯基乙醇(2-ME)和氯化亚锡(SnCl2)还原法进行标记,并用正交设计筛选最佳合成条件;对标记产物用纸层析法及Sephadex G-50层析柱分离测标记率;产物中分别加入牛血清白蛋白(BSA)、生理盐水及不同摩尔比的半胱氨酸(Cys)以观察其体外稳定性;用人脐静脉内皮细胞系ECV304观察其生物活性. 结果:2-ME法最佳标记条件为AS 100 μg,PB(0.5 mol*L-1, pH 7.3) 1 mL, 2-ME 100 μg, 亚甲基二膦酸盐(MDP)(用1 mL生理盐水溶解) 10 μL,加入99TcmO4- 185 MBq,标记率可达(97.0±1.5)%; SnCl2法为AS 100 μg,硼酸缓冲液(0.1 mol*L-1, pH 9.0) 1 mL, 20 g*L-1 SnCl2 (1 mol*L-1盐酸作为溶剂) 20 μL加入MDP药盒,用去氧水稀释至1 mL, 取20 μL,加入99TcmO4- 185 MBq,标记率可达(90.0±3.0)%. 产物在体外稳定;细胞培养观察其抑制内皮细胞生物活性与AS无显著差异. 结论:用99Tcm直接法标记AS简单高效,且对AS生物活性无明显影响.     

188Re-Herceptin-磁性纳米微粒的体外抗肿瘤作用

目的探讨^188Re—Herceptin-磁性纳米微粒在外置磁场下对HER-2／neu癌基因高表达的SKBR-3乳腺癌细胞的靶向结合性及抗癌作用。方法采用戊二醛交联法使人源性单克隆抗体Her—ceptin与磁性纳米微粒交联，用直接标记法制备^188Re—Herceptin及^188Re—Herceptin-磁性纳米微粒，用羰基铼标记法制备^188Re-磁性纳米微粒。肿瘤细胞体外抑制实验设4个组：^188Re—Herceptin-磁性纳米微粒组、^188Re—Herceptin组、^188Re-磁性纳米微粒组和^188ReO4^-组，各组均设3．7×10^4、18．5×10^4、37×10^4、55．5×10^4、74×10^4Bq／ml5个放射性剂量级别；另设生理盐水对照组。采用四甲基偶氮唑蓝（MTT）法测定各组的抑瘤效应，计算相对抑制率，采用半数抑制放射性浓度（IC50）对各组抑瘤作用进行比较和评价。结果^188Re—Herceptin-磁性纳米微粒和^188Re—Herceptin组对SKBR-3细胞均有较强杀伤作用，且呈剂量依赖性；而^188Re-磁性纳米微粒和^188Re04组的杀伤作用较弱0188Re—Herceptin-磁性纳米微粒组的IC50（53．1×10^4Bq／L）明显低于^188Re—Herceptin组（76．1×10^4Bq／L）；^188Re一磁性纳米微粒组和^188ReO4组的IC50分别为169×10^4和175×10^4Bq／L，明显高于前2组。结论^188Re—Herceptin-磁性纳米微粒和^188Re—Herceptin均可明显抑制体外培养的SKBR-3乳腺癌细胞增殖，且前者的抑制作用较后者强。