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21.
Kobayashi K Ishii S Kume K Takahashi T Shimizu T Manabe T 《The European journal of neuroscience》1999,11(4):1313-1316
From pharmacological studies, platelet-activating factor (PAF) has been proposed as a retrograde messenger for long-term potentiation (LTP) in the hippocampal CA1 region. We re-examined a possible contribution of PAF to LTP with a more specific approach using mice deficient in the PAF receptor. The PAF receptor-deficient mice exhibited normal LTP and showed no obvious abnormality in excitatory synaptic transmission. We also performed pharmacological experiments on the wild-type mice. Two structurally different antagonists of PAF receptors had no effects on LTP. Furthermore, the application of PAF itself caused no detectable changes in excitatory synaptic transmission. Thus, we conclude that the PAF receptor is not required for LTP in the CA1 region. Introduction 相似文献
22.
Emanuel Noam Kedar Eli Bolotin Elijah M. Smorodinsky Nechama I. Barenholz Yechezkel 《Pharmaceutical research》1996,13(6):861-868
Purpose. To evaluate benefits in tumor localization, availability, and noncancerous organ distribution of doxorubicin (DOX) delivered via small (120 nm) sterically stabilized immunoliposomes targeted against a tumor-associated antigen in fibrosarcoma-bearing mice.
Methods. DOX-loaded liposomes were prepared with (i) specific monoclonal IgG3 antibody (32/2, D-SSIL-32/2); (ii) non-specific IgG3 (D-SSIL-IgG); or (iii) no IgG (D-SSL) on their surface. Equal DOX amounts were injected intravenously via each type of liposome into BALB/c mice carrying experimental lung metastases of a polyoma virus-induced fibrosarcoma (A9 etc 220) expressing a polyoma virus-induced tumor-associated antigen (PAA) on their surface. Metastases occurred mainly in lung. Mice were treated at 3 stages of tumor development (micrometastases, medium-size metastases, and large, necrotic metastases). Performance evaluation was based on time-dependent quantification of DOX and DOX metabolites (DOX-M) in lung tumor, noncancerous organs, and plasma.
Results. (i) DOX delivered via both SSIL retained the prolonged circulation time typical of DOX delivered via D-SSL. (ii) DOX accumulation in noncancerous organs was similar for all preparations. Low levels of DOX-M were obtained for all three preparations in all organs except liver, suggesting a similar processing, (iii) Preparations differed in behavior in lung tumor depending on tumor size and microanatomy. Only at the micrometastases stage were the specifically targeted D-SSIL-32/2 superior to D-SSL and D-SSIL-IgG, delivering 2–4 times more drug into the tumor, (iv) DOX-M level in all three tumor stages was in the following order: D-SSIL-32/2 >> D-SSL >> D-SSIL-IgG, suggesting that DOX delivered as D-SSIL-32/2 is most available to tumor cells.
Conclusions. The advantage of specific targeting of sterically stabilized liposomes is expressed mainly in increasing availability of DOX to tumor cells in a way which is dependent on tumor microanatomy. The impact of this advantage to therapeutic efficacy remains to be determined. 相似文献
23.
Liver Targeting of Interferon Through Pullulan Conjugation 总被引:1,自引:0,他引:1
Xi Keli Tabata Yasuhiko Uno Kazuko Yoshimoto Miwa Kishida Tsunataro Sokawa Yoshihiro Ikada Yoshito 《Pharmaceutical research》1996,13(12):1846-1850
Purpose. The purpose of this study was to actively target interferon (IFN) to the liver through its chemical conjugation with pullulan, a water-soluble polysaccharide with a high affinity for the liver.
Methods. Chemical conjugation of IFN with pullulan was achieved by a cyanuric chloride method. Following intravenous injection of the conjugates to mice, their body distribution and the activity of an IFN-induced enzyme, 2,5-oligoadenylate (2-5A) synthetase in the liver and other organs, were evaluated.
Results. The cyanuric chloride method enabled us to prepare an IFN-pullulan conjugate that retained approximately 7–9 % of the biological activity of IFN. Pullulan conjugation enhanced the liver accumulation of IFN and the retention period with the results being reproducible. When injected intravenously to mice, the IFN-pullulan conjugate enhanced the activity of 2-5A synthetase in the liver. The activity could be induced at IFN doses much lower than those of free IFN injection. In addition, the liver 2-5A synthetase induced by conjugate injection was retained for 3 days, whereas it was lost within the first day for the free IFN-injected mice.
Conclusions. IFN-pullulan conjugation was promising for IFN targeting to the liver with efficient exertion of its antiviral activity therein. 相似文献
24.
Adrian L. Harris Huatang Zhang Amir Moghaddam Steve Fox Prudence Scott Adam Pattison Kevin Gatter Ian Stratford Roy Bicknell 《Breast cancer research and treatment》1996,38(1):97-108
Summary Several groups have shown that quantitation of tumor angiogenesis by counting blood vessels in primary breast cancer gives an independent assessment of prognosis. Poor prognosis is associated with high blood vessel counts. We have shown that the rate of cell division in endothelial cells is much higher in breast tumours than in normal breast. Breast cancer cell lines and primary human breast tumours express a wide range of vascular growth factors, including VEGF, placenta growth factor, pleiotrophin, TGF1, acidic and basic FGF, and platelet-derived endothelial cell growth factor. Inhibiting angiogenesis by blocking vascular growth factors would be difficult with highly specific agents, but drugs with a broader spectrum of antagonism may be effective. We have developed several suramin analogues which are less toxic than suraminin vivo but more potent in inhibiting angiogenesis, and these have been developed for Phase I. A combination of anti-angiogenesis agents with drugs activated by hypoxia may also be useful, because anti-angiogenesis alone may not kill cells, whereas activation of hypoxic drugs could synergize.New endpoints may be necessary because inhibition of new blood vessel formation may not cause tumour regression. Thus, the endpoint of stable disease and biochemical assessment of inhibition of angiogenesis may be much more important in therapeutic studies and for drug development in the future. The prognostic importance of angiogenesis suggests that this should be a major new therapeutic target.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb. 相似文献
25.
The treatment of infections caused by obligate or facultative intracellular microorganisms is difficult because most of the available antibiotics have either poor intracellular diffusion and retention or reduced activity at the acidic pH of the lysosomes. The need for antibiotics with greater intracellular efficacy led to the development of endocytosable drug carriers, such as liposomes and nanoparticles, which mimic the entry path of the bacteria by penetrating the cells into phagosomes or lysosomes. This Review assesses the potential of liposomes and nanoparticles in the targeted antibiotic therapy of intracellular bacterial infections and diseases and the pharmaceutical advantages and limitations of these submicron delivery systems. 相似文献
26.
中药和天然药靶向制剂的研究进展 总被引:6,自引:0,他引:6
靶向制剂可以提高靶组织的药理作用强度和降低全身的不良反应 ,是一种比较理想的给药方式 ,为第四代的药物剂型。采用脂质体作为药物载体是研究的重点 ,磁靶向 ,酶靶向制剂也是研究热点。此外 ,口服结肠靶向给药系统 (OCDDS)也是靶向制剂的一个重要部分 ,其是经口服将药物运送到回盲肠后释放并发挥局部或全身的治疗作用。中药靶向制剂的研究在我国还仅处于试探阶段 ,目前中药和天然药物的靶向制剂的研究大多数是以天然单一有效成分为原料药物 ,而用中药有效部位研制的靶向制剂屈指可数 ,这与制定中药有效部位的质量标准及制剂工艺难度大有关。中药新剂型和新技术的开展是中药国际化的关键 ,需要有组织地开展多学科合作 ,靶向制剂是中药今后发展的一个重要课题。 相似文献
27.
28.
纳米载体药物应用的研究进展纳米载体药物应用的研究进展 总被引:4,自引:0,他引:4
载体药物是随着药物学研究、生物材料科学和临床医学的发展而新兴的给药技术。药物通过载体进入人体 ,载体对药物吸附、包裹和键合 ,使药物释放部位、速度和方式等具有选择性和可控性 ,实现药物的缓释和靶向传输 ,从而更好地发挥药物治疗效率。载体药物技术的关键是载体材料的选择 ,目前已有各种高分子材料和无机材料被用于载体药物的研究 ,但对材料的选择必须满足组织、血液、免疫等生物兼容性的要求[1] 。此外 ,载体药物的制备也很重要 ,因为这将影响到载体药物的给药效率。最近已有很多方法应用于这一领域 ,纳米技术的应用已引起关注。纳… 相似文献
29.
RMP-7对两性霉素B脂质体跨血脑屏障能力的药效学研究RMP-7对两性霉素B脂质体跨血脑屏障能力的药效学研究 总被引:3,自引:0,他引:3
目的研究两性霉素B脑靶向脂质体对小鼠脑膜炎的治疗作用。方法用薄膜超声法制备两性霉素B脂质体和两性霉素B脑靶向脂质体,测定其包封率和浓度;建立小鼠的脑膜炎模型,研究了两性霉素B脂质体的疗效。结果两性霉素B脂质体的包封率为(93.3±1.8)%;脑内注射白色念珠球菌2 h使小鼠形成脑膜炎模型;将两性霉素B制成脑靶向脂质体,能显著延长脑膜炎小鼠的生存期。结论与普通两性霉素B脂质体相比,两性霉素B脑靶向脂质体能显著提高对小鼠脑膜炎的治疗作用,使小鼠的存活期延长一倍。 相似文献
30.
新药研究中的前药原理 总被引:2,自引:0,他引:2
前药具有改变药物的理化性质 ,提高生物利用度 ,增加水溶性 ,减少不良反应 ,定位到达靶器官等特性。前药保持或增强原药的药效 ,同时又克服了原药的缺点。本文主要综合前药原理在新药设计中的典型实例 ,介绍前药原理的应用规律 相似文献