超氧自由基O2-与人的血癌和心肌炎

本报告系采用间接法——分光光度法测定成人、小儿血癌患者及心肌炎小儿血中红细胞的超氧化物歧化酶(简称SOD)活性,以观察O_2~-水平。和正常人的相比 ,患参与之有非常显著(或显著)差异。心肌炎患者滴注大剂量维生素丙,(简称Vc)后,则SOD活性上升至正常水平。它初步提示:间接法适用于人体O_2~-的观察;血癌和心肌炎的发生确与SOD活性或O_2~-水平有关;在剂量Vc对心肌炎的治疗作用也和SOD活性或O_2~-水平的变化有关。     

Inhibitory effects of ethyl acetate and butanol fractions from Morinda lucida benth on benzene-induced leukemia in mice

IntroductionMorinda lucida Benth has been traditionally reported as a remedy for the treatment of cancer as well as Leukemia in Africa. Therefore, this study was aimed at screening fractions of M. lucida for potential anti-leukemia constituents and activities in mice.Methodsleukemia was induced with intra-peritoneal administration of benzene. Fractions of M. lucida were administered by oral gavaging in mice and screened for anti-leukemia and anti-clastogenic activities. The liver sections were assessed for hepatoprotective activity and possible anti-leukemia compounds in fractions were analysed using GC-MS. Docking analysis was done to understand the mechanism of anti-leukemic activity.ResultsSignificant (p < 0.05) anti-leukemic activity was observed in the ethyl acetate and n-butanol fractions while prevention of chromosomal and liver damage was exhibited by all the fractions. GC-MS analysis of the fractions revealed anti-leukemic constituents. The identified constituents showed promising pharmacokinetic properties and inhibitory potential against certain proteins involved in cancer development.ConclusionOverall, the anti-leukemic activity observed in this study might be attributed to the antioxidant, apoptotic induction, cell cycle control, and anti-inflammatory properties of M. lucida fractions.     

Spatial regression analysis between air pollution and childhood leukaemia in Portugal

This study aims to investigate whether known carcinogenic chemical elements in atmospheric deposition might be associated with child mortality due to leukemia in the Portuguese population. A Bayesian hierarchical model was used to explore the association between lichen biomonitoring measurements of four elements—As, Hg, Ni, Pb—and childhood leukemia death counts taken at small administrative units. This geographical epidemiological study found a non-significant positive association between the risk of childhood leukemia and levels of arsenic, mercury and lead, and a non-significant negative association between the disease and the level of nickel. Lead seems to show a weaker association with childhood leukemia than arsenic and mercury.     

尿多胺含量与血液系统恶性肿瘤关系的研究——毛细管气相色谱分析尿中多胺

用毛细管色谱柱配以氮磷检测器测定尿中多胺,对几例白血病患者和正常人尿中多胺定性和半定量。结果表明白血病患者尿中多胺总量高于正常人;化疗后较化疗前尿多胺含量明显降低。本法在临床诊断、治疗监视和预后方面均有重要意义。     

白血病人血清的31P NMR研究

运用³¹P核磁共振波谱(NMRS)研究血清中磷脂的代谢变化,并探讨该法对白血病诊断的可行性.方法采用MSL-300MHz型超导核磁共振仪测量白血病人及健康人血清标本,通过分析比较血清中磷脂酰胆碱(PC)信号及磷脂酰乙醇胺和(神经)鞘磷脂(PE+SM)信号相对积分面积,了解各自血清中的磷脂含量水平.结果,白血病人 血清中的磷脂信号强度相对正常人明显偏低,反映了对应的PC及(PE+SM)含量相对正常人偏低,尤其对初发未治疗的病人,差别更加明显.结论,本法可作为研究血清中磷脂的变化、代谢情况及白血病人临床诊断的新方法.     

Pharmacokinetics and tissue distribution of the antileukaemic organoarsenicals arsthinol and melarsoprol in mice

Melarsoprol and arsthinol have been shown to be effective on various leukaemia cell lines. Nevertheless, the tissue distribution of these compounds remains a key point since the bone marrow is considered as the site of action and the central nervous system as the site of the main toxicity. In this study, we have determined the exposure of each organ (blood, liver, bone marrow and brain) to arsenic, irrespectively of the exact nature of arsenic species contained by the organ.In the bone marrow, arsenic concentrations were very high, especially that of melarsoprol. However, the lower ability of arsthinol to concentrate in the bone marrow could be compensated by its higher antileukaemic activity.The brain concentrations were high, although lower than in the bone marrow; this fact is in very good accordance with the observation that the brain is mainly involved in the acute toxicity of trivalent organoarsenicals.     

A Comparative Study of Water T1 and T2 Nmr Relaxation Times in Healthy and Pathological Blood Fluid

Water protons T₁ and T₂ relaxation times in samples of whole blood, obtained from healthy people and from patients affected by Macrocytic Anemia on one side and Lymphatic and Myeloid Leukemia on the other, have been measured with the FT NMR technique at 80 Mhz and at 25 °C. No significant difference with respect to the value of the spin lattice relaxation time parameter measured for the healthy control group is experimentally evident in the case of the Macrocytic Anaemia while the spin spin relaxation time increases in magnitude. On the reverse both the leukemic cases present a significant (p < 0.001) increase in the relaxation times with respect to the control group. The experimental relaxation data belonging to the anaemic case show a linear correlation with the red cells volume while that obtained for the two leukaemic cases appear linearly correlated with the total white cell numbers. From the relaxation data an estimate of the amount of water tightly bound to the white cells membrane can be determined which results roughly thirty times lower than that bound to the red cells membrane. In this work is also presented a step by step outline of the water relaxation behavior which starts with the pure water and ends with the water in the whole blood supported by relaxation experiments done on the isolated blood main components.     

Study of Aldo-keto Reductase 1C3 Inhibitor with Novel Framework for Treating Leukaemia Based on Virtual Screening and In vitro Biological Activity Testing

Aldo-keto reductase 1C3(AKR1C3) is a potential target for the treatment of acute myeloid leukaemia and T-cell acute lymphoblastic leukaemia. In this study, pharmacophore models, molecular docking and virtual screening of target prediction were used to find a potential AKR1C3 inhibitor. Firstly, eight bacteriocin derivatives(Z1-Z8) were selected as training sets to construct 20 pharmacophore models. The best pharmacophore model MODEL_016 was obtained by Decoy test(the enrichment degree was 21.5117, and the fitting optimisation degree was 0.9668). Secondly, MODEL_016 was used for the virtual screening of ZINC database. Thirdly, the hit 83256 molecules were docked into the AKR1C3 protein. Compared to the total scores and interactions between compounds and protein, 16532 candidate compounds with higher docking scores and interactions with important residues PHE306 and TRP227 were screened. Lastly, eight compounds(A1-A8) that had good absorption, distribution, metabolism, excretion and toxicity(ADMET) properties were obtained by target prediction. Compounds A3 and A7 with high total score and good target prediction results were selected for in vitro biological activity test, whose IC₅₀ values were 268.3 and 88.94 μmol/L, respectively. The results provide an important foundation for the discovery of novel AKR1C3 inhibitors. The research methods used in this study can also provide important references for the research and development of new drugs.     

Towards high-throughput single cell/clone cultivation and analysis

In order to better understand cellular processes and behavior, a controlled way of studying high numbers of single cells and their clone formation is greatly needed. Numerous ways of ordering single cells into arrays have previously been described, but platforms in which each cell/clone can be addressed to an exact position in the microplate, cultivated for weeks and treated separately in a high-throughput manner have until now been missing. Here, a novel microplate developed for high-throughput single cell/clone cultivation and analysis is presented. Rapid single cell seeding into microwells, using conventional flow cytometry, allows several thousands of single cells to be cultivated, short-term (72 h) or long-term (10-14 days), and analyzed individually. By controlled sorting of individual cells to predefined locations in the microplate, analysis of single cell heterogeneity and clonogenic properties related to drug sensitivity can be accomplished. Additionally, the platform requires remarkably low number of cells, a major advantage when screening limited amounts of patient cell samples. By seeding single cells into the microplate it is possible to analyze the cells for over 14 generations, ending up with more than 10 000 cells in each well. Described here is a proof-of-concept on compartmentalization and cultivation of thousands of individual cells enabling heterogeneity analysis of various cells/clones and their response to different drugs.