附子理中丸方药的药物动力学研究

附子理中丸是中医治疗脾胃虚寒、脘腹冷痛、呕吐泄泻、手足不温的常用成药。本文通过小白鼠急性死亡实验,测得ip LD_(50)=42.4870g/kg;运用药物累积法对该复方方药进行了药物动力学研究。结果表明:附子理中丸在小鼠体内按一级动力学消除,呈二房室开放式模型分布。测得其t_(1/2)α=0.1922h,t_(1/2)β=11.2888h等动力学参数。阐明了该药的体内动态过程,为评价该药的内在质量及临床安全合理应用提供了参考依据。     

雷公藤多甙对小鼠Ⅳ型超敏反应影响的研究

采用动物实验，选择Ⅳ型超敏反应局部渗出性改变、Ｔ细胞增殖能力的强弱和病理形态学观察等指标，研究了雷公藤多甙（ＴｒｉｐｔｅｒｙｇｉｕｍＷｉｌｆｏｒｄｉｉＰｏｌｙｇｌｙｃｏ－Ｓｏｄｉｕｍ，ＴＷＰ）对ＯＴ诱导的Ⅳ型超敏反应小鼠模型的影响。结果表明，经ＴＷＰ灌胃９～１５天的小鼠，发敏的局部渗出性改变明显降低，与未给药的模型组相比，Ｐ＜０．０５，病理形态学观察结果亦与之相符。ＴＷＰ的这种作用可能与已报道的其多种免疫抑制效应有关。     

Induction of Experimental Antiphospholipid Antibody Syndrome in PL/J Mice Following Immunization With β2GPI

PROBLEM: Immunization with β₂-glycoprotein I (β₂GPI) induces antiphospholipid antibodies (aPL) in normal mice and rabbits. Recently we reported early onset of autoimmunity in MRL/++ mice following immunization with β₂GPI. There is a close association between aPL with thrombosis, recurrent fetal loss, and intrauterine growth retardation. In this study we evaluated the effect of β₂GPI-induced aPL on pregnancy outcomes in an inbred strain of mice (PL/J). METHOD: Three groups of seven-week-old female PL/J mice (12 per group) were studied. Group A was immunized with β₂GPI and group B with ovalbumin; group C was not immunized. After two booster injections, the mice were tested for aPL, anti-DNA by ELISA, and for ANA by indirect immunofluorescence. Platelet count and pregnancy outcomes were studied at the age of 14 weeks. RESULTS: The aPL and anti-DNA levels were higher at 12 and 14 weeks in group A; the optical densities (OD) were 1.72±0.6 and 0.699±0.25 for group A, 0.091 ±0.040 and 0.230±0.47 for group B, and 0.0435±0.003 and 0.119±0.026 for group C (comparing group A with groups B and C combined, P<0.001). ANA titers rose in groups A and B by age, but they were significantly higher at 14 weeks in group A. The mean titers were 1/286, 1/90, and 1/16 for A, B, and C, respectively (P<0.001). The platelet counts were not significantly different among the three groups. The litter size was significantly smaller in group A, as evidenced by the numbers of viable fetuses among the mice that became pregnant in each group: 0.75, 2.45, and 5.5 in groups A, B, and C, respectively. Seven pregnant mice in group A had complete resorption, seven pregnant mice in group B showed focal (partial) resorption areas, and only one mouse in group C had complete resorption of the embryos, as shown by histopathological studies, although the fecundity rate was similar in the three groups. CONCLUSION: Our data suggest a pathogenic role for β₂GPI-induced aPL in the development of experimental models of APS in PL/J mice.     

乌苯美司的药物动力学及对实验性肿瘤转移的治疗作用

目的：探讨乌苯美司对小鼠药物动力学及与实验性肿瘤转移治疗活性间的关系。方法：用放射免疫法测定小鼠在不同给药途径下的乌苯美司血清药物动力学及观察乌苯美司对黑色素瘤肺转移模型的治疗活性。结果：乌苯美司ｉｖ的Ｔ１２较短，初始血药浓度较高。ｉｖ和ｉｍ给药后的曲线下面积较大；ｐｏ及ｉｐ则较小。不同给药途径对实验性肿瘤转移均有治疗作用。结论：乌苯美司的血清Ｔ１２较短，其治疗活性取决于冲击和高剂量的给药方式。     

In vivo and in vitro anti-tumour response of selenium-protein polysaccharide extracted from rich selenium Agaricus blazei

In this study, the anti-tumour activity of selenium-protein polysaccharide (SPP), a water extract of the rich selenium Agaricus blazei, was tested both in vivo and in vitro. The results of in vivo experiments show that SPP at doses of 50 and 100 mg/kg inhibits proliferation of implanted Sarcoma 180 by 22 and 37.69%, respectively, and promotes lymphocyte transformation and natural killer (NK) cells activity in tumour bearing mice. During the in vitro experiment, we treated the tumour and non-tumour bearing mice with SPP, and prepared serum treated with SPP (Serum_SPP). The results show that Serum_SPP, whether from tumour or non-tumour bearing mice, significantly inhibits K562 cells proliferation and induces their apoptosis, and also significantly increases caspase-3 activity of K562 cells. However, the difference in anti-tumour activity of Serum_SPP between tumour and non-tumour bearing mice is significantly different (p<0.01). The results, according to the studies both in vivo and in vitro, imply that SPP extracted from rich selenium A. blazei can inhibit growth of implanted Sarcoma 180 and promote lymphocyte transformation and NK cells activity in vivo. Additionally, Serum_SPP can inhibit proliferation and cause apoptotic morphological changes and the fragmentation of internucleosomal DNA, and increase caspase-3 activity of K562 cells in vitro, which indicates that apoptosis of K562 cells induced by Serum_SPP may be related to up-regulation of caspase-3.     

Protective immunity to malaria: studies with cloned lines of rodent malaria in CBA/Ca mice. IV. The specificity of mechanisms resulting in crisis and resolution of the primary acute phase parasitaemia of. Plasmodium chabaudi chabaudi and P. yoelii yoelii

Low numbers of parasites from cloned lines of the rodent malaria parasites, Plasmodium chabaudi chabaudi AS and P. yoelii yoelii A, injected into CBA/Ca mice produce acute but usually self-limiting infections. During crisis, i.e. 1-2 days after peak parasitaemia, 'pre-immune' mice experiencing such 'background' infections were reinfected intravenously with homologous parasites or parasites of heterologous strains or species. P. c. chabaudi AS pre-immune mice controlled an AS challenge with essentially the same kinetics as the background infection. Reinfection of AS pre-immune mice with the heterologous (CB and IP-PCI) P. c. chabaudi strains or P. chabaudi adami DS had little effect on the initial growth of these parasites, although eventually the parasitaemia was controlled. In contrast, a partial inhibitory effect on the growth of P. vinckei lentum DS was evident. Challenge with the non-lethal (A) or lethal (YM) variants of P. y. yoelii resulted in an increase in both the growth and virulence of these parasites. P. y. yoelii A pre-immune mice controlled a homologous challenge, but were less effective at controlling the YM variant. In addition, they were unable to clear rapidly a P. c. chabaudi AS or P. v. lentum DS challenge. Both the multiplication and virulence of P. berghei ANKA were enhanced. These findings demonstrate that resolution of the primary acute parasitaemia in P. c. chabaudi AS- and P. y. yoelii A-infected mice is predominantly mediated by species- and strain-specific mechanisms.     

枸杞多糖对运动性骨骼肌疲劳恢复的细胞定量化学分析和电镜观察

通过小鼠实验，用枸杞多糖解除运动性骨骼肌疲劳，以显微分光光度计进行琥珀酸脱氢酶(SDH)和糖原的定性定量分析，并于透射电镜下观察超微结构的变化。结果显示，运动疲劳(B)组糖原含量明显降低，各类肌纤维与对照(A)组比较P<0．001。SDH活性增加，各类肌纤维与A组比较P<0．001。服用枸杞多糖(C)组糖原含量增加，各类肌纤维与A组之较P<0．001；与B组比较P<0．001；SDH反应较B组更深，各类肌纤维与A组比较P<0．001，若与B组比较，则其中Ⅰ(慢肌)型和Ⅱ(中间肌)型P<0．001，而Ⅱ(快肌)型则P>0．05。超微结构显示，B组线粒体增多且体积明显增大，呈肿胀状态，C组全无此类改变，提示服用枸杞多糖后可解除疲劳，其中以Ⅰ(慢肌)型肌纤维效果尤佳。     

新型饮水对小鼠繁殖及抗氧化酶活性的影响

目的　探讨新型饮水对健康的影响及其保健作用。方法　将矿溶生态水、活化水、纯净水、矿泉水、碱性离子水等 5种新型饮水作为唯一水源分别喂饲亲代及子代小鼠 3个月 ,对照给予天然水。观察它们对小鼠体重、繁殖及抗氧化酶活性的影响。结果　与天然水比较 ,活化水、矿溶生态水促进亲代雄性小鼠体重增长 (P <0 0 5) ;矿溶生态水使子代小鼠、矿泉水和碱性离子水使子代雄性小鼠体重增长缓慢 (P <0 0 5) ;纯净水使新生仔鼠体重减轻 (P <0 0 5) ,活化水、矿溶生态水使小鼠窝产仔数增多 (P <0 0 5) ,5种水对小鼠受孕率、妊娠率、出生存活率无影响 ;矿溶生态水、活化水、纯净水、矿泉水使小鼠肝组织SOD活力升高 (P <0 0 5) ,碱性离子水使肝组织SOD活力降低 (P <0 0 5)。结论　 5种新型饮水对小鼠体重有影响 ,对受孕率、妊娠率、出生存活率无影响 ;矿溶生态水、活化水、纯净水、矿泉水有提高SOD活力作用     

Cell proliferation in human tumours growing in nude mice: renal cell carcinomas,larynx and hypopharynx carcinomas

Summary Cell proliferation of 51 human renal cell carcinomas and 9 larynx and hypopharynx carcinomas has been studied in vitro and using xenotransplants. The proliferative activity ([³H]thymidine labelling index) increases during the first passages in nude mice and then remains almost constant throughout subsequent passages. A comparison of cell kinetic parameters of 8 human renal cell carcinomas, 1 hypopharynx and 2 larynx carcinomas, with data of xenografts and of human tumours in situ published up to now, shows that the cell kinetic parameters of human tumour xenografts presently studied range between those of human tumours in situ and those of autochthonous or transplantable mouse tumours. S-phase durations and potential doubling times are considerably shorter in xenotransplants than in human tumours in situ, whereas the cycle time is about the same. This means that the growth fraction increases considerably after xenotransplantation. This change of human tumour cell proliferation after transplantation into nude mice should be kept in mind if one wishes to draw conclusions from the nude mouse model on conditions in human beings, particularly with respect to therapeutic regimens, which are frequently tested in the nude mouse model.Abbreviations used RCC renal cell carcinoma - HPC larynx or hypopharynx carcinoma - LI labelling index - PLM percentage of labelled mitoses - t _s S-phase duration - t _c cycle time - t _pot potential doubling time This work was supported by the Deutsche Forschungsgemeinschaft (Ma 876/2-1)     

Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4

Interleukin (IL)-2 and IL-4 are considered as important regulators of growth and differentiation of lymphocytes. We report that in mice made deficient for both IL-2 and IL-4 by gene targeting all major T cell subsets and B cells were normal, indicating that IL-2 and IL-4 are not essential for development of the immune system. Paradoxically, proliferation of T cells was increased in both IL-2- and IL-4-deficient homozygous mice.