Detailed toxicity studies of liposomal gadolinium-DTPA.

Acute, subacute, and delayed toxicity testing was assessed in mice for liposomal gadolinium-DTPA (Gd-DTPA), blank liposomes, and nonliposomal Gd-DTPA. In the subacute experiments mice were injected intravenously (IV) with 0.3 mmol/kg Gd-DTPA per day for 30 days in the form of either free Gd-DTPA, liposomal Gd-DTPA, or an equivalent amount of lipid in blank liposomes without Gd-DTPA. The interpolated acute LD50 of liposomal and nonliposomal Gd-DTPA, estimated as a means of identifying the approximate level, was similar (LD50 = 5.7 mmol/kg Gd-DTPA). In subacute toxicity testing, prolonged high doses of liposomal Gd-DTPA caused splenomegaly, cardiomegaly, lymphocytopenia and hypergammaglobulinemia (P less than .05). Nonliposomal Gd-DTPA caused mild cardiomegaly and altered liver enzymes (P less than .05). Blank liposomes caused relatively mild splenomegaly (P less than .05) but few other changes. Delayed testing three months after the subacute testing showed that most of the changes caused by the liposomal Gd-DTPA were reversible.     

Biodistribution and clearance of liposomal gadolinium-DTPA

Gadolinium-DTPA (Gd-DTPA) liposomes have been studied previously as liver contrast agents and have been shown to improve the detection of hepatic metastases in rats. We synthesized 100-nm and 50-nm liposomes that encapsulated Gd-DTPA and did biodistribution and clearance studies in rats. Parallel magnetic resonance imaging (MRI) studies were also done. Biodistribution showed a prolonged blood pool phase for Gd-DTPA liposomes with a blood pool half-life of approximately 4 hours for the 100-nm liposomes. The highest uptake per gram of tissue was achieved by the spleen. Clearance of gadolinium from the liver and spleen showed a half-life of 3 to 4 days. The smaller 50-nm Gd-DTPA liposomes resulted in a longer blood pool phase and a higher delivery of gadolinium to the liver, bone marrow, and spleen. Imaging studies after intravenous (IV) administration of liposomal Gd-DTPA showed organ enhancement that paralleled the data on biodistribution studies, with appreciable hepatic enhancement at doses as low as 0.025 mm/kg of liposomal Gd-DTPA.     

An improved method for the preparation of [11C]verapamil.

This paper describes an improved preparation of [11C]verapamil by reaction of [11C]methyl triflate with desmethylverapamil. The optimal reaction temperature, amount of precursor and reaction time were assessed. With this method [11C]verapamil can be prepared with a reproducible radiochemical yield of 66 +/- 4% (EOB, based on [11C]methyltriflate). Total synthesis time was 60 min. Radiochemical purity was >99% and specific activities varied between 5 and 30TBq/mmol.     

一种改进的用于测定细胞周期的细胞制备方法

目的 :减少细胞的聚集数量 ,提高测试效率和结果的准确性。方法 :在用酒精固定细胞时分别加入终浓度为 0 % ,1.5 % ,3% ,6 %和 12 %的小牛血清 ,置 - 2 0℃分别固定细胞 1d ,3d和 7d。比较了不同浓度的血清和保存不同时间粘连细胞的数量及对细胞周期分析结果的影响。结果 :加入血清可明显减轻细胞的粘连 ,减少了细胞的聚集数量 ,尤以 3%小牛血清组最佳。样品可不必过滤 ,在上机测试时 ,进样针不堵塞 ,上样速度快 ,细胞周期分析更准确。随着保存时间的延长 ,聚集细胞的数量有增加的趋势。结论 :在制备用于测定细胞周期的样品时 ,固定细胞的过程中加入终浓度为 3%的小牛血清是一种简单的、能有效地保护细胞膜使细胞不易粘连的技术措施 ,且固定细胞的时间不宜超过 7d。     

Clearance of liposomal gadolinium: in vivo decomplexation.

The contrast agents gadolinium-DTPA (diethylenetriaminepentaacetic acid), Gd-DOTA (tetraazacyclododecanetetraacetic acid), and Gd-HP-DO3A (1,4,7-tris[carboxymethyl]-10-[2' hydroxypropyl]-1,4,7,10-tetraazacyclododecane) are used in humans as extracellular contrast agents. Although free Gd+ ion is toxic, the intact Gd3+ complexes are rapidly excreted and are relatively nontoxic. Decomplexation with release of free gadolinium is a relevant clinical concern in patients with altered renal clearance. Blood pool contrast agents currently under development may have longer clearance half-lives and be more prone to decomplexation. The present study was designed to evaluate the clearance of liposomally encapsulated Gd3+ complexes (DTPA, DOTA, and HP-DO3A). The macrocyclic compounds had more rapid and complete clearance than DTPA (P less than .05). Parallel studies with carbon-14 and Gd-153-labeled complexes showed significant differences (P less than .05) in the amount of these isotopes retained in the heart, kidney, lungs, and spleen, providing strong supportive evidence for in vivo decomplexation.     

An improved method for the quantification of left-to-right cardiac shunts.

We have investigated a technique for quantifying QP/QS in left-to-right cardiac shunts. In this method, the gamma variate, which is fitted to the first-pass portion of the lung curve, is used to generate a curve, which simulates the response of a normal lung curve with systemic recirculation. The difference between this curve and the observed lung curve is then used to calculate QP/QS. This method was evaluated on a set of simulated lung time-activity curves with precisely known QP/QS values on a group of 11 patients with no clinical suspicion of cardiac shunt and on a group of 30 patients referred for cardiac shunt studies. The QP/QS in each of these studies was determined by three individuals using both the Maltz-Treves method and the new method. This method yielded QP/QS values that were more accurate on the simulated lung data and had less interobserver variation on all the studies than those obtained from the Maltz-Treves method.     

An improved method for inducing hypothermia and rewarming.

A hypothermia and rewarming system combining body surface and ventilatory heat exchange is described. The method utilizes body surface heat exchange through conduction, convection, and black body radiation, and ventilatory heat exchange across the lung surface through conduction, convection, and water evaporation. The system consisted of a chamber in which the temperature was maintained at a desired level (+/- 2.5 degrees C) using a refrigeration-heat pump unit. Chamber temperatures during cooling and rewarming were -15.5 +/- 2.7 degrees C and 43.2 +/- 2.3 degrees C, respectively. Inhalate temperatures during cooling were -8.2 +/- 6.5 degrees C and during rewarming they were 41.5 +/- 0.3 degrees C. Helium (100%) was supplied to the chamber, while the animal was ventilated with 20% O2 + 80% He. Under these conditions, the cooling and rewarming rates were 0.33 +/- 0.06 degrees C/min and 0.20 +/- 0.04 degrees C/min, respectively, at 38--21 degrees C. The system provided for rapid cooling and rewarming with no evidence of any untoward effects.     

An alternative method of bowel preparation for barium enemas.

A double blind trial is described comparing two methods of bowel preparation prior to barium enema. In 40 randomly selected patients a significant improvement was obtained by the use of an intestinal perfusion method.     

一种改进的溶血素测定法

目的：改进溶血素测定方法。方法：在待测样品中加入Ｓｙｓｍｅｘ公司生产的快速溶血剂－Ⅱ,用半自动生化仪测Ｄ５４０,计算出样品半数溶血值ＨＣ５０。结果：用该方法测定联苯双酯、环磷酰胺和阿司匹林３种已知药物对绵羊红细胞（ＳＲＢＣ）致敏小鼠产生溶血素的影响,分别为无作用、抑制和增强,与以往文献报道的结果一致。结论：改进的溶血素测定法操作简单省时,可以用于药物筛选和药效评价。     

T1 relaxivity of core-encapsulated gadolinium liposomal contrast agents--effect of liposome size and internal gadolinium concentration

RATIONALE AND OBJECTIVES: Long circulating core-encapsulated gadolinium (CE-Gd) liposomal nanoparticles that have surface conjugated polyethylene glycol are a promising platform technology for use as blood pool T1-based magnetic resonance (MR) contrast agents. The objective of this study was to investigate the effect of liposome size and internal (core) Gd concentration on the T1 relaxivity of CE-Gd liposomes. MATERIALS AND METHODS: Twelve different liposomal formulations were synthesized and characterized, resulting in a size (50, 100, 200, and 400 nm) and core Gd-concentration (200, 350, and 500 mM) "matrix" of test samples. Subsequently, CE-Gd liposomes were diluted in deionized water (four diluted samples) and molar T1 relaxivity (r1) measurements were performed at 2- and 7-T MR field strengths. RESULTS: The r1 of CE-Gd liposomes was inversely related to the liposome size. The largest change in r1 was observed between liposomes that were extruded through 50- and 100-nm filter membranes. At both field strengths, the variation in internal gadolinium concentration did not show any significant correlation (alpha 相似文献   

An improved method for the radiotherapy of breast carcinoma

This method of radiotherapy of the breast and lymph nodes in cases of breast cancer reduces exposure of the lung and features small gaps and overlaps at the borders of neighbouring fields. The outline of fields, the design of special absorbing blocks and filters, and some notes on treatment planning are given in this paper.     

Four-dimensional MR microscopy of the mouse heart using radial acquisition and liposomal gadolinium contrast agent.

Magnetic resonance microscopy (MRM) has become an important tool for small animal cardiac imaging. In relation to competing technologies (microCT and ultrasound), MR is limited by spatial resolution, temporal resolution, and acquisition time. All three of these limitations have been addressed by developing a four-dimensional (4D) (3D plus time) radial acquisition (RA) sequence. The signal-to-noise ratio (SNR) has been optimized by minimizing the echo time (TE) (300 us). The temporal resolution and throughput have been improved by center-out trajectories resulting in repetition time (TR) <2.5 ms. The contrast has been enhanced through the use of a liposomal blood pool agent that reduces the T(1) of the blood to <400 ms. We have developed protocols for three specific applications: 1) high-throughput with spatial resolution of 87 x 87 x 352 um(3) (voxel volume = 2.7 nL) and acquisition time of 16 min; 2) high-temporal resolution with spatial resolution of 87 x 87 x 352 um(3) (voxel volume = 2.7 nL) and temporal resolution at 4.8 ms and acquisition time of 32 minutes; and 3) high-resolution isotropic imaging at 87 x 87 x 87 um(3) (voxel volume = 0.68 nL) and acquisition time of 31 min. The 4D image arrays allow direct measure of cardiac functional parameters dependent on chamber volumes, e.g., ejection fraction (EF), end diastolic volume (EDV), and end systolic volume (ESV).     

An improved method for acquiring cerebrovascular reactivity maps

This study aims to improve the method used to produce cerebrovascular reactivity (CVR) maps by MRI. Previous methods have used a standard boxcar presentation of carbon dioxide (CO₂). Here this is replaced with a sinusoidally modulated CO₂ stimulus. This allowed the use of Fourier analysis techniques to measure both the amplitude and phase delay of the BOLD CVR response, and hence characterize the arrival sequence of blood to different regions of the brain. This characterization revealed statistically significant relative delays between regions of the brain (ANOVA < 0.0001). In addition, post hoc comparison showed that the frontal (P < 0.001) and parietal (P = 0.004) lobes reacted earlier than the occipital lobe. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

An improved method for STR analysis of bloodstained denim

Indigo dye is used to dye denim and other fabrics. It is now accepted that if this is co-extracted with the DNA, it may inhibit PCR amplification. A simple, improved method is described for the extraction of DNA from bloodstained denim for PCR amplification and short tandem repeat (STR) analysis. The DNA was extracted by constructing a blotting system using capillary action to draw a saline solution through the denim. The transferred material was collected onto nylon membranes and these were processed by chelex extraction. A variety of coloured denim substrates and other heavily dyed fabrics, including case work samples were used. In all cases the DNA was extracted, amplified and typed correctly. Received: 8 December 1997 / Received in revised form: 13 August 1998     

一种改进的大鼠脑组织灌注固定方法

目的：改进常规脑灌注固定方法存在着一些不足，使其组织结构更佳，提高灌注效率。方法：改进灌注针头和灌注液，改变灌注的循环通路。结果和结论：提高了灌注效率，节省灌注时间和灌注液，结构更加清晰，结果可靠。为有关脑组织的各种常规病理形态、免疫组化、原位杂交、原位PCR的实验研究提供了一种更加简便、快捷、有效可行的方法。