188Re诱导肿瘤细胞凋亡的实验研究

采用MTT法，光镜，电镜，流式细胞仪和免疫组化方法研究了^188Re诱导三种肿瘤细胞凋亡的形态学变化，剂量时间效应关系以及凋亡相关基因Bcl-2和Bax在其中的表达情况。结果表明：^188Re对三种肿瘤细胞有明显的杀伤效应，能效导其产生凋亡的形态学变化，并且随着浓度的增大和时间的延长，凋亡率增加，Bcl-24表达减弱，Bax表达增强，二者比值下降;细胞阻滞于G2／M期，三种肿瘤细胞对^188Re的敏感性由高到低依次为PC－3细胞，ER－75－30细胞，A549细胞。     

188Re-HEDP注射液药物代谢动力学研究

将药物静脉注射到动物体内 ,以观察188Re -HEDP注射液在动物体内代谢动力学的特征。结果表明 ,滞留在荷瘤大鼠患骨中的放射性比在正常骨中的多 (P <0 .0 5 ) ;小鼠 72h内排泄放射性累积百分率约为 82 %(其中尿液排泄为 80 %) ;体外血浆蛋白结合率为 86 .4 %± 0 .30 %。说明该药物是亲骨药物 ,血清除快符合药物代谢动力学二室模型 ,大部分的药物以原形从肾排出。     

No Direct Postconditioning Effect of Poloxamer 188 on Mitochondrial Function after Ischemia Reperfusion Injury in Rat Isolated Hearts

Myocardial infarction is a leading cause for morbidity and mortality worldwide. The only viable treatment for the ischemic insult is timely reperfusion, which further exacerbates myocardial injury. Maintaining mitochondrial function is crucial in preserving cardiomyocyte function in ischemia reperfusion (IR) injury. Poloxamer (P) 188 has been shown to improve cardiac IR injury by improving cellular and mitochondrial function. The aim of this study was to show if P188 postconditioning has direct protective effects on mitochondrial function in the heart. Langendorff prepared rat hearts were subjected to IR injury ex-vivo and reperfused for 10 min with 1 mM P188 vs. vehicle. Cardiac mitochondria were isolated with 1 mM P188 vs. 1 mM polyethylene glycol (PEG) vs. vehicle by differential centrifugation. Mitochondrial function was assessed by adenosine triphosphate synthesis, oxygen consumption, and calcium retention capacity. Mitochondrial function decreased significantly after ischemia and showed mild improvement with reperfusion. P188 did not improve mitochondrial function in the ex-vivo heart, and neither further P188 nor PEG induced direct mitochondrial protection after IR injury in this model.     

中位-四[二-(3,4-羧甲氧基)苯基]卟啉及其结合Re=O的初步研究

用密度泛函理论的B3LYP法,将中位-四[二-(3,4-羧甲氧基)苯基]卟啉及结合Re=O分子的几何构型优化,初步理论研究其前沿轨道和能量等。证明,与单独的卟吩环相比,T_(3,4)CPP的卟吩环平面性良好,环上的结构参数变化很小;Re=O与T_(3,4)CPP卟吩环的结合能明显大于与T_(3,4)CPP侧链羧基的结合能,且前者所形成配合物的稳定性显然高于后者,说明T_(3,4)CPP与~(188)Re=O结合的位点应在卟吩环上,而不在侧链羧基上。T_(3,4)CPP卟吩环结合Re=O而形成配合物的结构参数,与Vicente等Zn-卟啉衍生物的测定值相近。在卟吩环上配位时,T_(3,4)CPP卟吩环上的电荷重新分布,卟吩环碳原子的电子向4个氮原子转移:配位后,卟吩环的几何构型略收缩(0.14 A-0.19 A)和马鞍形扭转(5.7°)。     

放射性药物~(188)Re标记DTPA的制备和在大鼠体内的分布

球囊导管内充盈β放射性核素防治经皮冠状动脉成形术(PTCA)后再狭窄是一种崭新的技术, 其中,188Re是一种常用的放射性核素。为了尽可能降低在万一球囊破裂的情况下高剂量放射性对人体的损害,利用二乙三胺五醋酸(DTPA)迅速从泌尿系统排出的特点,通过探索188Re标记DTPA的方法和条件,成功地制备了188Re-DTPA化合物,并研究出最佳的标记条件从而使标记产率达到90%以上。188Re-DTPA和188ReO4-在大鼠体内分布的研究结果显示,甲状腺和胃肠道的放射性水平188Re-DTPA组明显低于188ReO4-组,188Re-DTPA经肾脏排泄明显快于188ReO4-,用MIRDOSE 3.0软件估算体内重要脏器的吸收剂量同样也显示了这一结果。188Re-DTPA组和188ReO4-组甲状腺的吸收剂量分别为0.041 nGy/Bq和0.563 nGy/Bq,胃的吸收剂量分别为0.043 nGy/Bq和0.118 nGy/Bq。因此,实验结果认为在血管内照射治疗中188Re-DTPA明显优于188ReO4-。     

Enhanced Oral Bioavailability of Ibuprofen in Rats by Poloxamer Gel Using Poloxamer 188 and Menthol

To improve the oral bioavailability of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution and pharmacokinetic study of ibuprofen delivered by the ibuprofen-loaded preparations composed of poloxamer 188 and menthol were then performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio of menthol to ibuprofen showed an abrupt increase in the solubility of ibuprofen. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/mL. The simultaneous addition of menthol and poloxamer 188 significantly improved the dissolution rates of ibuprofen from aqueous solution due to the ibuprofen solubility-improving effect of menthol in the presence of poloxamer. Furthermore, the ibuprofen-loaded preparation with menthol and poloxamer 188 gave significantly higher initial plasma concentrations, Cmax, and AUC of ibuprofen than did the preparation without menthol and poloxamer 188, indicating that the simultaneous addition of menthol and poloxamer 188 could improve the oral bioavailability of ibuprofen in rats. In modern pain management it is always desirable for the ibuprofen-loaded preparation with poloxamer 188 and menthol to show a rapid onset of action with a minimal phase of lag time to feel the decreased pain. From an industry point of view, it is more desirable for a formulation to be fast acting, easy to use, and cost effective. Thus, the ibuprofen-loaded preparation with poloxamer 188 and menthol was a more effective oral dosage form for poorly water-soluble ibuprofen.     

Polymeric Titanium Oxychloride Sorbent for 188W/188Re Nuclide Pair Separation

Abstract

The chemical synthesis conditions (TiCl₄: iPrOH reagent ratio and reaction temperature scheme) were optimized for the preparation of polymeric titanium oxychloride sorbent which met the requirements for clinically useful ¹⁸⁸W/¹⁸⁸Re generator production, such as high W-adsorption capacity, high ¹⁸⁸Re-elution yield, low ¹⁸⁸W-breakthrough, and good mechanical stability. This polymeric material was formed by polycondensation of titanium-oxychloride units, the chemical formula of which was supposed as [OTiO (Ti₄₀ Cl₈₀ (OH) ₈₀ (TiO₂)₉₅.60H₂O) OTiO]_n. The effect of the W-content of tungstate solution on the WO₄ ^2? ion adsorption (with minimizing the poly-tungstate ion adsorption) and its covalent bonding with the Ti metal atoms in the polymeric matrix were justified with respect to the optimal W-adsorption conditions for the preparation of a useful ¹⁸⁸W/¹⁸⁸Re generator column. The high W-adsorption capacity of about 515.6 mg W/g sorbent and ¹⁸⁸Re elution yield of higher than 85% wereachieved. The large difference in the distribution ratio values found for alumina and polymeric titanium oxychloride sorbent in 0.005% NaCl solution (D_{W, Re-188} = 50 and D_{W, Re-188} = 1.0, respectively) offered an advantage for the preparation of a consecutive-elution based ¹⁸⁸Re generator system which combined both ¹⁸⁸Re elution and ¹⁸⁸Re concentrating processes in one portable system. This generator system is of a tandem column type which consists of a polymeric titanium oxychloride sorbent coupled to an alumina column. This system gave a ¹⁸⁸Re concentration factor of approximately 10. The overall ¹⁸⁸Re yield achieved from this system was >80%. ¹⁸⁸W isotope and elemental tungsten breakthrough were not detected in its ¹⁸⁸Re eluate. This system thus offers a potential application for clinically useful ¹⁸⁸Re production using low specific radioactivity ¹⁸⁸W (around 500 mCi/g) producible in a medium neutron flux reactor.     

高速RS(204,188)译码器的FPGA实现

介绍了数字电视广播中广泛采用的RS(204,188)译码器原理和FPGA实现方案,采用并行的三级流水线结构以提高速度,并根据Berlekamp-Massey(BM)算法对译码器进行了优化设计,减少了硬件消耗.译码器的最大时钟频率可以达到75MHz.译码器的性能仿真和FPGA实现验证了该方案的可行性.     

Rhenium labeled McAb—SZ39 and colloid

Two kinds of rhenium labeled radiopharmaceuticals for therapy of the human brain glioma were prepared.Anti-human brain glioma monoclonal antibody (McAb-SZ39) was directly labeled with 186 ReO4^-.When ascorbic acid was used as reduction agent of antibody and the reduction of 186 ReO4^- was finished in sodium gluconate solution(pH=2.54),the labeling efficiency was 96.2%,After purification,the labeled products were tested in respect of immunoreactivity,in vitro stability as well as inhibitory efficiency against human glioma transplanted in nude mice,188ReO4^- labeled colloid was synthesized by using a two-step method.The size of radiocolloid particles was around 2-5μm,and the radiochemical yield was over 95%,Nude mice Experiments demonstrated that the inhibitory efficiency against human brain glioma of 188Re-collied and ^188 Re-McAb-SZ39 was 90% and 65% ,respectively.     

Pre-treatment and ethanol fermentation potential of olive pulp at different dry matter concentrations

Renewable energy sources have received increased interest from the international community with biomass being one of the oldest and the most promising ones. In the concept of exploitation of agro-industrial residues, the present study investigates the pre-treatment and ethanol fermentation potential of the olive pulp, which is the semi solid residue generated from the two-phase processing of the olives for olive oil production. Wet oxidation and enzymatic hydrolysis have been applied aiming at the enhancement of carbohydrates' bioavailability. Different concentrations of enzymes and enzymatic durations have been tested. Both wet oxidation and enzymic treatment were evaluated based on the ethanol obtained in a subsequent fermentation step by Saccharomyces cerevisiae and Thermoanaerobacter mathranii. It was found that a four-day hydrolysis time was adequate for a satisfactory release of glucose and xylose. The combination of wet oxidation and enzymatic hydrolysis resulted in the glucose and xylose concentration increase of 138 and 444%, respectively, compared to 33 and 15% with only enzymes added. However, the highest ethanol production was obtained when only enzymic pre-treatment was applied, implying that wet oxidation is not a recommended pre-treatment process for olive pulp at the conditions tested. It was also showed that increased dry matter concentration did not have a negative effect on the release of sugars, indicating that the cellulose and xylan content of the olive pulp is relatively easily available. The results of the experiments in batch processes clearly emphasize that the simultaneous saccharification and fermentation (SSF) mode is advantageous in comparison with the separate hydrolysis and fermentation (SHF) mode concerning process contamination.