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排序方式: 共有1331条查询结果,搜索用时 31 毫秒
1.
《药学学报(英文版)》2020,10(7):1294-1308
A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents. 相似文献
2.
顺铂聚乳酸微球的药物释放特性及肝动脉栓塞研究 总被引:5,自引:0,他引:5
对顺铂聚乳酸微球进行了体外药物释放和家犬肝动脉栓塞研究。该微球粒径范围为50~200μm,平均粒径为115.76±35.94μm,顺铂含量为37.16%(W/W);体外药物释放机制符合Higuchi方程;肝动脉栓塞后8h,肝组织顺铂浓度高达21.55±12.18μg/g,明显高于肝动脉灌注顺铂组:3.16±0.09μg/g(P<0.05);肝动脉栓塞组的顺铂血浓峰值、各取血点浓度及曲线下面积AUC皆低于肝动脉灌注顺铂组。可望达到提高栓塞部位的药物疗效,降低全身毒副反应的作用。 相似文献
3.
为了了解吉林省长白县山区所产卫矛科雷公藤属植物黑蔓的药理作用,扩大它的药用部位和应用范围,我们从无机元素与中药药效有密切关系的角度出发,实验测出黑蔓含有Ba、Si、Cu、Fe、Zn、Sn、Co、Mn、Mg、Ca、Se等无机元素,本文重点对其中人体必需的微量元素Cu、Fe、Zn、Se作了定量分析。 相似文献
4.
5.
空管药物疗法治疗牙髓病和根尖周病疗效观察 总被引:1,自引:0,他引:1
用SMTD复合药物对牙髓病和根尖周病实施空管药物疗法。78例103颗获得完整随访资料患牙经两年观察,92.2%治愈率。文章介绍了治疗方法,讨论了空管药物疗法的愈合机理、优点、失败原因及其预防措施。 相似文献
6.
Lomber SG Payne BR Hilgetag CC Rushmore J 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2002,142(4):463-474
A contralateral hemineglect of the visual field can be induced by unilateral cooling deactivation of posterior middle suprasylvian (pMS) sulcal cortex of the posterior parietal region, and this neglect can be reversed by additional cooling deactivation of pMS cortex in the opposite hemisphere. The purpose of the present study was to test whether an enduring hemianopia induced by removal of all contiguous visual cortical areas of one hemisphere could be reversed by local cooling of pMS cortex in the opposite hemisphere. Two cats sustained large unilateral ablations of the contiguous visual areas, and cooling loops were placed in the pMS sulcus, and in contact with adjacent area 7 or posterior ectosylvian (PE) cortex of the opposite hemisphere. In both instances cooling of pMS cortex, but neither area 7 nor PE, restored a virtually normal level of orienting performance to stimuli presented anywhere in the previously hemianopic field. The reversal was highly sensitive to the extent of cooling deactivation. In a third cat, cooling deactivation of the superficial layers of the contralateral superior colliculus also restored orienting performance to a cortical ablation-induced hemianopia. This reversal was graded from center-to-periphery in a temperature-dependent manner. Neither the cortical ablation nor any of the cooling deactivations had any impact on an auditory detection and orienting task. The deactivations were localized and confirmed by reduced uptake of radiolabeled 2-deoxyglucose to be limited to the immediate vicinity of each cooling loop. The results are discussed in terms of excitation and disinhibition of visual circuits. 相似文献
7.
Visual evoked potentials (VEPs) elicited by foveal presentation of words were compared to brain potentials evoked by the same words in a condition where subjects had to make a saccadic eye movement in order to perceive the words (saccade-related brain potentials, SRPs). Subjects had to categorize the words responding with a button press to stimuli belonging to the target (infrequent, P = 0.2) category. The VEP and SRP waveforms showed divergences in the early (up to 250 ms) components, but a marked similarity between the late components. Principal Component Analysis also revealed the same relationship between the two types of brain responses. Peak latency of the late SRP components measured from saccade offset showed an apparent processing advantage over the corresponding late components of VEPs. The N3 component, indexing semantic processing of visual patterns, peaked between 310 and 375 ms in the SRPs, while in the VEPs it appeared between 410 and 470 ms. The P4 component, associated with final stimulus evaluation, showed a similar latency benefit in favour of SRPs (420-500 ms vs 530-590 ms in VEPs). The mean reaction time was 74 ms shorter in the eye movement condition (measured from saccade offset) than in the VEP condition (703 vs 777 ms). The question of what kind of processes may contribute to the differences in mean RTs and to the latencies of the late components between the two conditions are discussed. We suggest that the late components (P3, N3 and P4) of the VEP and the SRP, respectively, index identical brain processes. 相似文献
8.
Urethane anesthetized (< 1 .3 g/kg), Sprague-Dawley (SD) rats spontaneously cycled between a cortically desynchronized state (State I) and a cortically synchronized state (State III), which were very similar to awake and slow wave sleep (SWS) states in unanesthetized animals, based on EEG criteria. These low levels of urethane anaesthesia did not cause significant respiratory depression or reductions in sensitivity to hypoxia (10% O2 in nitrogen) or hypercapnia (5% CO2 in air) in rats in either State I or State III. Thus, breathing frequency (fR), tidal volume (VT) and total ventilation (VTOT) all increased on cortical activation in urethane-anaesthetized rats whether breathing air, the hypoxic or the hypercapnic gas mixture, in a manner that was very similar to that observed in unanaesthetized animals. The relative sensitivity to hypoxia was greater in State III than State I, the relative sensitivity to CO2, overall, was equal in both states, State III occurred less often during hypoxia and hypercapnia, and hypoxic, urethane-anaesthetized rats sighed frequently, particularly in State I. This is also similar to the situation seen in unanesthetized rats. Given the similarities seen between urethane anesthetized rats in the present study and literature values for unanesthetized rats, the data suggest that urethane-anaesthetized rats provide a good model system for studying respiratory patterns and chemoreflexes as a function of cortical activation state. 相似文献
9.
We have determined cutaneous DTH reactions to SK-SD and PPD and peripheral blood lymphocyte profiles in a group of asbestos workers in two consecutive surveys. It was found that asbestosis and, to a lesser extent, the presence of ANA are significantly correlated with the lack of response to the above antigens. 83% of asbestos workers when tested at a 4 year interval fell into the same two categories of responsiveness (lack of response or response at least to one antigen).The asbestosis cases had lower total lymphocyte count as well as proportions and absolute number of E-RFC as compared to asbestos workers without asbestosis and/or ANA. Furthermore, the latter group showed the lower percentages and absolute number of E-RFC than the matched controls. The presence of ANA is also correlated with lower proportions of E-RFC. However, this is related at least in part to asbestosis. 相似文献
10.
An autoradiographic method combined with a rosette technique was used to assess the bactericidal activity of individual control and inflammatory peritoneal macrophages (PM phi) in the presence or absence of expression of Fc receptor for IgG (FcR). There was a lack of FcR reactivity in a certain percentage of both categories of PM phi exposed to E. coli X43, a bacterium which is readily phagocytosed in the presence of specific antibody. Both rosetting and non-rosetting PM phi were capable of phagocytosing E. coli X43, but inflammatory PM phi showed a marked reduction in their capacity to ingest these bacteria compared with control PM phi. Once ingested the E. coli X43 were killed equally well by non-rosetting and rosetting control and inflammatory PM phi. 相似文献