Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy

BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immunocompromised patients. Echinocandins are novel antifungal molecules with in vitro and in vivo activity against Aspergillus species. METHODS: We investigated the efficacy and safety of caspofungin in the treatment of IA. Ninety patients with IA who were refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B, or triazoles were enrolled to receive caspofungin. RESULTS: Efficacy was assessed for 83 patients who had infection consistent with definitions of IA and who received >or=1 dose of study drug. Common underlying conditions included hematologic malignancy (48% of patients), allogeneic blood and marrow transplantation (25% of patients), and solid-organ transplantation (11% of patients). Seventy-one patients (86%) were refractory to and 12 patients (14%) were intolerant of previous therapy. A favorable response to caspofungin therapy was observed in 37 (45%) of 83 patients, including 32 (50%) of 64 with pulmonary aspergillosis and 3 (23%) of 13 with disseminated aspergillosis. Two patients discontinued caspofungin therapy because of drug-related adverse events. Drug-related nephrotoxicity and hepatotoxicity occurred infrequently. CONCLUSION: Caspofungin demonstrated usefulness in the salvage treatment of IA.     

不同发育阶段人表皮干细胞端粒酶反转录酶表达的比较

目的:目前已知端粒酶活性的丧失及其增殖相关基因表达的改变是造成多种成体干细胞体外复制和扩增受限的主要原因,而端粒酶反转录酶对端粒酶活性起关键作用。体外分离培养人胚胎、少儿、成人3种不同皮肤来源的表皮干细胞,对比观察不同发育阶段端粒酶反转录酶表达的差异。方法:实验于2005-09/2007-04在南昌大学第一附属医院烧伤研究所完成。①对象:因创伤等原因致意外流产的妊娠24～26周龄胎儿皮肤标本,4～12周岁少儿及25～45岁成年人烧伤整形植皮手术剩余皮片标本,分别由南昌大学第一附属医院产科、烧伤科提供,产妇与烧伤患者对治疗及实验均知情同意,实验经医院医学伦理委员会批准。②实验方法:取胎儿、少儿和成年人的全层皮肤,用胰蛋白酶和EDTA联合消化法分离表皮,胶原快速贴附法纯化人表皮干细胞,用未黏附的角质细胞作为对照,以含表皮生长因子、角质细胞无血清培养液组成的表皮干细胞培养基进行体外培养。③实验评估:通过β_1整合素、角蛋白19、p63免疫细胞化学染色对培养细胞进行鉴定,计算克隆形成率。以免疫细胞化学染色法和图像定量分析法检测3种不同皮肤来源的表皮干细胞端粒酶反转录酶的表达差异。结果:①细胞生长特征:分离培养的人表皮干细胞呈明显克隆性生长,克隆形成率高于角质细胞对照组(P<0.05)。②表皮干细胞的鉴定:细胞克隆经免疫细胞化学染色后,β_1整合素、角蛋白19、p63均呈阳性表达。③端粒酶反转录酶免疫细胞化学染色及定量表达:不同皮肤来源的表皮干细胞端粒酶反转录酶均呈阳性,但表达强度不同,人胚胎>少儿>成人。3种皮肤来源的表皮干细胞平均吸光度值和阳性面积值均随年龄增加而逐渐降低,人胚胎>少儿>成人(P<0.05)。结论:人胚胎、少儿、成人皮肤来源的表皮干细胞均有端粒酶反转录酶表达,其表达强度依次减弱。提示诱导和增强端粒酶反转录酶的表达对维持表皮干细胞在体外自我更新和增殖能力可能具有重要意义。     

Identification and characterization of a high-affinity granulocyte- macrophage colony-stimulating factor receptor on primary rat oligodendrocytes

We previously showed the presence of receptors for granulocyte- macrophage colony-stimulating factor (GM-CSF) on tumor tissues and tumor cell lines that are derived from the neural crest. To determine whether normal neural cells express functional GM-CSF receptors, we isolated and analyzed primary rat brain cells, including microglia, astrocytes, and oligodendrocytes. Scatchard analysis of equilibrium binding of 125I-GM-CSF to primary rat oligodendrocytes showed an average of 1,110 GM-CSF binding sites per cell, with a kd of 20 pmol/L. In six separate experiments, no specific binding was detectable on the astrocyte population. Microglia were used in competitive binding experiments with oligodendrocytes, and addition of microglia did not increase the specific binding of labeled ligand to oligodendrocytes. In dose-response assays, we measured 3H-thymidine uptake in rat oligodendrocytes, microglia and control murine 32D cells stimulated with various concentrations of GM-CSF. Over concentration ranges of 0.025 to 1000 pmol/L, cell proliferation and peak 3H-thymidine incorporation was observed at approximately 30 pmol/L for both the control cells and the oligodendrocytes. However, the microglial cells did not proliferate in response to GM-CSF. These data indicate the presence of a functional receptor for GM-CSF on primary rat oligodendrocytes, and suggest that hematopoietic growth factors such as GM-CSF may play a role in nerve cell development, function, or response to injury.