Polymeric prodrugs of mitomycin C designed for tumour tropism and sustained activation

Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents.     

Effects of citrate on the different phases of calcium oxalate crystallization

Urinary citrate appears to be an important factor in the crystallization process of calcium oxalate and calcium phosphate. The urinary excretion of citrate was found to be significantly lower in patients with calcium oxalate stone disease as compared with normal subjects, and about 30 per cent of the calcium stone formers can be considered as hypocitraturic. The lowest excretion of citrate was recorded in urine collected during the night. Citrate has significant effects on supersaturation with respect to both calcium oxalate and calcium phosphate, it also inhibits the growth of these crystals. In addition, citrate appears to be capable of inhibiting the aggregation of crystals composed of calcium oxalate, brushite, and hydroxyapatite. The heterogenous growth of calcium oxalate on calcium phosphate is also counteracted by citrate. As a consequence of the crucial role of citrate in these processes, stone prevention with alkaline citrate has become an attractive form of treatment in patients with recurrent stone formation. Single evening dose administration of sodium potassium citrate resulted in an of sodium potassium citrate resulted in an increased excretion of citrate, reduced levels of the calcium/citrate ratio as well as supersaturation with respect to calcium oxalate and a decreased rate of stone formation. However, conflicting results of stone preventive treatment with alkaline citrate have been reported by different groups, and long-term follow-up of patients treated in a randomized way is necessary to definitely assess the efficacy of alkaline citrate.     

HPMBP与伯胺N_(1923)对希土元素(Ⅲ)的协同萃取

本文研究了HPMBP与伯胺N_(1923)的二甲苯溶液,从盐酸介质中协同萃取希土(Ⅲ)的机理。用斜率法、恒摩尔法确定了协萃配合物的组成为:RNH_3Ln(PMBP)_4。求得关于Pr(Ⅲ)协萃反应的平衡常数及协萃配合物的生成常数分别为:logK_(12)=-1.95;logβ_(12)=3.94。实验发现,协萃系数(R)随希土元素的原子序数(Z)递变而呈现“双峰效应”。还研究了协萃配合物的IR,NMR谱。     

生态平衡的伦理学意蕴解读

20世纪以来，人类采用技术工程治理、法律制裁和经济惩罚等措施，一定意义上改善了局部的生态环境，但是未能遏制住全球环境问题的恶化态势。生态危机的根本解决，关键在于人类自身必须进行深刻的利益观念和价值观念的变革。重新审视人与自然界的关系，对自然进行伦理关怀，寻求和建立以保护地球环境和人类生存与可持续发展的生态平衡理念。     

Diameter NASREQ协议在卫星移动通信系统中的应用研究

如何对接入网络的用户进行身份认证、授予相应权限并进行计费,是卫星移动通信系统网络管理需解决的重要问题。简要介绍认证、授权、计费(AAA)的基本概念,分析Diameter协议框架、协议原理以及协议应用于网络接入的特点。阐述协议中包含的各种应用,给出Diameter NASREQ应用的一种系统模型。重点研究Diameter NASREQ协议在卫星移动通信系统中的应用,详述应用中客户机和服务器中各模块的功能和工作原理。通过分析,说明该应用的可行性及有效性。