The average number of alpha-particle hits to the cell nucleus required to eradicate a tumour cell population

Alpha-particle emitters are currently being considered for the treatment of micrometastatic disease. Based on in vitro studies, it has been speculated that only a few alpha-particle hits to the cell nucleus are considered lethal. However, such estimates do not consider the stochastic variations in the number of alpha-particle hits, energy deposited, or in the cell survival process itself. Using a tumour control probability (TCP) model for alpha-particle emitters, we derive an estimate of the average number of hits to the cell nucleus required to provide a high probability of eradicating a tumour cell population. In simulation studies, our results demonstrate that the average number of hits required to achieve a 90% TCP for 10(4) clonogenic cells ranges from 18 to 108. Those cells that have large cell nuclei, high radiosensitivities and alpha-particle emissions occurring primarily in the nuclei tended to require more hits. As the clinical implementation of alpha-particle emitters is considered, this type of analysis may be useful in interpreting clinical results and in designing treatment strategies to achieve a favourable therapeutic outcome.     

A Solubility and Related Physicochemical Property Comparison of Buprenorphine and Its 3-Alkyl Esters

Pharmaceutical Research -     

Monocyte chemotaxis and chemotactic cytokine release after exposure to hydroxyethyl starch

Hydroxyethyl starch (HES) is commonly used in leukapheresis and infused as an alternative to blood components for the treatment of hypotension due to hemorrhage and trauma. Its prolonged intravascular persistence and retention in tissue raise concerns about possible effects on humoral and cell-mediated immunity and white cell (WBC) locomotion, particularly in volunteer WBC donors or in severely burned individuals with immunologic depression and increased risk for infection. This study evaluated the effect of HES on human monocyte migration and chemotaxis and the production of antigen- and mitogen-induced WBC-derived chemotactic cytokine. A bioassay was developed to quantitate the neutrophil chemotactic activity of a cytokine generated by mononuclear WBCs stimulated in vitro by phytohemagglutinin or tuberculin protein. The time- and dose-dependent generation of the chemotactic cytokine was not affected by the presence of HES. HES by itself did not induce the generation of this cytokine, nor were human monocyte chemotaxis and spontaneous migration significantly changed by exposure to HES. These results, with those of other investigators, suggest that HES is a safe red cell-sedimenting agent for leukapheresis and an alternative to the use of blood components in shock resuscitation.     

甲真菌病治疗指南

该指南是英国皮肤科医师协会针对皮肤科医生制定的 ,反映了当前文献报道中的最新研究资料。在解释这些资料时应慎重 ,因为未来的研究可能会改变现有的结论或推荐方案。在应用该指南时 ,需因人而异 ,因地制宜。遵守指南并不能确保万无一失 ,因此对实施指南时的偏离不应都归咎于疏忽 (该指南并不能保证面面俱到 ,在实际应用中可加以变通 )。简介 :甲真菌病是最常见的皮肤病之一。英国对 10 0 0 0人进行的一项大规模问卷调查显示发病率为 2 71%。芬兰和美国最近的真菌学对照调查表明 ,发病率为 7%～ 10 %。甲真菌病发病率的升高和有效抗真菌新…