吲哚胺2,3-双加氧酶(IDO)的色胺酮类抑制剂筛选及其体外抗肿瘤作用

 目的  评价色胺酮衍生物吲哚胺2,3-双加氧酶 (indoleamine 2,3-dioxygenase,IDO)的抑制活性,并研究其作为 IDO 抑制剂的抗肿瘤作用。方法  采用基因工程手段表达、纯化重组人 IDO (rhIDO),建立 IDO 活性检测体系;以色胺酮衍生物作为对象,进行 IDO 抑制活性初筛,对抑制类型、半数抑制浓度以及抑制常数进行测定;构建高表达人 IDO 的 pcDNA3.1(+) hIDO 转染 HEK 293 细胞,评价色胺酮衍生物在细胞水平上的 IDO 抑制活性;采用 MTT 比色法考察色胺酮衍生物3对人非小细胞肺癌A549细胞的生长抑制作用。结果  6个被测色胺酮衍生物均具有IDO抑制活性,且细胞水平上的抑制效力高于酶活水平,抑制效力均优于目前通用的IDO抑制剂1 甲基色氨酸(1-methyl-tryptophan,1-MT)。色胺酮衍生物 3 作为最强的 IDO 抑制剂,其Ki值为 0.161 μmol/L。MTT 实验结果显示,色胺酮衍生物3 显著抑制 A549 细胞生长,IC50 为 8.77 μmol/L。结论  色胺酮衍生物是一类新型高效的 IDO 抑制剂,在体外对 A549 细胞具有较强的抗肿瘤活性。     

The clinical workstation

We have spent many years hearing about the benefits that we are about to reap from computers, but often seem to find that workloads are increased rather than decreased by the demands for ever more complex data. I certainly hope that the possibilities being offered up in this review represent more than idle dreams, and may be the first signs of computer systems that genuinely help to reduce our workload.     

Acid-base properties of thymopoietin-type tri- and tetrapeptides and their derivatives

The submolecular basicities of 21 immuno-modulating, thymopoietin-type di-, tri-, and tetrapeptides were studied and characterized in terms of group constants and partial microconstants. All compounds were derivatives of the H-Arg-Lys-Asp-OH tripeptide. Modifications within four covalent bonds of the basic site (esterification, acylation, curtailment or addition at C-terminal end, exchange of amino acids) cause significant changes in the scheme of protonation and in the individual basicity of proton binding sites. Configurational changes of the component amino acids, however, do not cause significantly different basicities in the diastereomers.     

Hemorrhagic intracranial malignant neoplasms: spin-echo MR imaging

Twelve patients with 15 separate, spontaneously hemorrhagic, intracranial malignant lesions (seven primary gliomas, eight metastatic lesions) were examined with spin-echo magnetic resonance imaging at 1.5 T, and with computed tomography. The signal intensity patterns of these lesions, as seen on both short repetition time (TR)/short echo time (TE) and long-TR/long-TE spin-echo pulse sequences, were compared with the previously described appearance at 1.5 T of non-neoplastic intracerebral hematomas. The images of hemorrhagic intracranial malignancies showed notable signal heterogeneity, often with identifiable nonhemorrhagic tissue corresponding to tumor; diminished, irregular, or absent hemosiderin deposition; delayed hematoma evolution; and pronounced or persistent edema, compared with non-neoplastic hematomas. The demonstration of these characteristics in the appropriate clinical setting may suggest malignancy as the cause of an intracranial hematoma.     

Fat suppression by section-select gradient reversal on spin-echo MR imaging. Work in progress

A method to decrease the intensity of fat by reversal of the section-select gradient is demonstrated. This technique takes advantage of the chemical shift in section location.     

Intracranial hemorrhage: gradient-echo MR imaging at 1.5 T. Comparison with spin-echo imaging and clinical applications

Fifty-seven patients with hemorrhagic intracranial lesions were examined with magnetic resonance (MR) imaging at 1.5 T with use of both spin-echo (SE) and gradient-echo-acquisition (GEA) techniques to assess the clinical applications and limitations of GEA in evaluation of intracranial hemorrhage at high field strength. All GEA images were obtained with a long echo time and short flip angle to emphasize T2*-based contrast. In 30 of 61 cases, GEA images demonstrated more hemorrhagic lesions than SE images. In 14 of 61 cases, GEA images failed to depict the lesion or obscured the specific diagnosis (as depicted by SE MR imaging). The authors believe that GEA imaging in its current form has a limited but definite adjunctive role in the evaluation of intracranial hemorrhage at high field strength.