979 resultados para Chronic problems
Resumo:
An augmented immersed interface method (IIM) is proposed for simulating one-phase moving contact line problems in which a liquid drop spreads or recoils on a solid substrate. While the present two-dimensional mathematical model is a free boundary problem, in our new numerical method, the fluid domain enclosed by the free boundary is embedded into a rectangular one so that the problem can be solved by a regular Cartesian grid method. We introduce an augmented variable along the free boundary so that the stress balancing boundary condition is satisfied. A hybrid time discretization is used in the projection method for better stability. The resultant Helmholtz/Poisson equations with interfaces then are solved by the IIM in an efficient way. Several numerical tests including an accuracy check, and the spreading and recoiling processes of a liquid drop are presented in detail. (C) 2010 Elsevier Ltd. All rights reserved.
Resumo:
Numerical simulations of the multi-shock interactions observable around hypersonic vehicles were carried out by solving Navier-Stokes equations with the AUSMPW scheme and the new type of the IV interaction created by two incident shock waves was investigated in detail. Numerical results show that the intersection point of the second incident shock with the bow shock plays important role on the flow pattern, peak pressures and heat fluxes. In the case of two incident shocks interacting with the bow shock at the same position, the much higher peak pressure and more severe heat transfer rate are induced than the classical IV interaction. The phenomenon is referred to as the multi-shock interaction and higher requirements will be imposed on thermal protection systems.
Resumo:
何首乌为常用中药,由何首乌及含何首乌的中成药制剂所引起的不良反应也时见报道,科学阐明不良反应的物质基础并提出解决方案对何首乌的使用十分重要。本论文研究了何首乌炮制前后KM小鼠肝脏毒性基因表达谱、生物活性及化学成分的变化。所获结果支持何首乌炮制的目的是减毒、改性(改变药效),何首乌生、熟异治的观点。制首乌对抑郁症的效果显著优于生首乌,这与本草所记载的何首乌炮制后补肝肾、益精血,归肝、肾经一致。 主要结果如下: 1、 生、制首乌的毒理基因芯片研究结果 何首乌的不良反应主要表现在肝损害方面。本研究建立了生何首乌和制何首乌不同剂量的肝毒性作用模型,体重指标统计发现生何首乌各剂量组平均体重显著下降,中剂量组(10 g/kg.d)体重下降20 %,高剂量组(20 g/kg.d)体重下降42%,50%动物死亡,提示动物机体能量代谢障碍;基因芯片研究结果表明何首乌是CYP450的抑制剂,生何首乌相对于制何首乌CYP3A4、CYP4A5显著下调,导致毒性成分在体内的吸收增加,服用大剂量的生何首乌后产生明显的肝毒性;主要对以下六条Pathway产生影响:①PPAR signaling pathway,主要毒性靶基因有RXRB CYP7a1、Acadl、Apoa2、Cyp4a、 FABP2 、MAPKKK5等基因。②Calcium signaling pathway,主要毒性靶基因有CAMK2B、CACNA1F、S100A1、 F2R、Ryr1、Slc8a2、Camk4 ③Neuroactive ligand-receptor interaction,主要毒性靶基因有Chrm4、 Ntsr2 、 GABRR1、 GRIK3、F2R等基因。④Wnt signaling pathway,主要毒性靶基因有Daam2、Rac1 等基因。⑤Complement and coagulation cascades,主要毒性靶基因有F2R、Serpina1b、Cfi 、FGA等基因。⑥Oxidative hosphorylation,主要毒性靶基因有Atp5e、NDUFA1等基因。生何首乌毒性明显强于制首乌,且生何首乌水煎液的毒性大于生何乌首丙酮提取物的毒性,这一结果表明,何首乌主要的毒性成分很可能并不仅仅是传统所认为的以大黄素为代表的蒽醌类化合物,而是何首乌中大量存在的有效组分二苯乙烯苷与大黄素相互作用的结果,这一研究结果与前述的何首乌对肝药酶的影响是一致的。后续生、制首乌的化学成分差异研究表明,炮制后二苯乙烯苷含量明显降低:生首乌为5.512 %、清蒸制首乌为3.811 %、豆制首乌为3.538 %,大黄素的含量炮制后显著升高,生首乌为0.094 %、清蒸制首乌为0.119 %、豆制首乌为0.126 %。 2 生、制首乌药效差异研究结果 本文采用慢性中等强度不可预知应激刺激模型(chronic unpredictable mild stress, CUMS)和动物行为绝望实验法,研究生、制首乌抗抑郁活性的差异,制首乌(5 g/kg.d)与模型组相比有显著差异(P< 0.01),生首乌制首乌(5g/kg.d)与模型组相比无显著差异,这一结果表明制首乌抗抑郁活性显著优于生首乌。 本文比较了生、制首乌对四氧嘧啶糖尿病模型小鼠血糖的影响的差异,生首乌(5 g/kg.d)与模型组相比有显著差异(P< 0.01),制首乌(5 g/kg.d)与模型组相比无显著差异,这一结果表明生首乌降糖活性优于制首乌。这一结果与历代中医古书中生首乌治疗消渴症(糖尿病)的记载一致。 3生、制首乌化学成分差异的研究结果 本文选用HPLC-DAD指纹图谱技术结合药效成分含量测定来研究生、制首乌化学成分的差异。炮制后,何首乌中的主要化学成分并未消失,只是其含量发生了改变。炮制后二苯乙烯苷含量明显降低:生首乌为5.512 %、清蒸制首乌为3.811 %、豆制首乌为3.538 %,大黄素的含量炮制后显著升高,生首乌为0.094 %、清蒸制首乌为0.119 %、豆制首乌为0.126 %。 综上所述,炮制前后何首乌中二苯乙烯苷和大黄素含量比的变化可能是何首乌炮制减毒、改性的物质基础。 根据上述结果我们建立了生、制首乌的质量控制新模式。 In recent years, some adverse drug reactions (ADR) about some traditional Chinese medicine were reported at times. As a Chinese medicine most in use, the ADRs of Radix Polygoni multiflori (RPM) and the medicines containing the RPM were also mentioned. The resolution of the problems caused by the ADRs is very important for the use of the RPM as a medicine. The process (or preparation) is a significant feature for the clinical use of the Chinese medicine and an important technology for the safe use and good effect of the Chinese medicine. By processing, the toxicity of the Chinese medicine can be reduced, its properties can be changed and curative effect can be enhanced at the same time. The changes of the gene expression profiles for KM mice hepatotoxic effects, and the change of the biological activity and the chemical composition after being processed of the RPm were studied in the present dissertation. The RPm heatotoxicity mechanism and the toxicity target genes were explained on the gene level for the first time. With the antidepressant activity, and the hypoglycemic effect as the target, the differences on the pharmacodynamics between the processed RPm and unprocessed RPm, for the first time, were investigated. The results obtained show that the antidepressant activity of the processed RPM is far higher than the ones of unprocessed RPm. As we know, the results were reported for the first time. The quality control systems (QCS) for the processed and the unprocessed RPm were founded. The HPLC-DAD was used in the systems founded on the basis of the toxicology and the pharmacodynamics experiments. As we know, the OCSs were reported for the first time. The above-mentioned experimental results confirm that the unique process theory of the traditional Chinese medicine (TCM) used for the process of the Radix Polygoni multiflori (RPm) is correct, i.e after being processed the toxicity of the RPm decreases and its Pharmacodynamic effects change. It is known to author that there have been no similar reports in the literatures up to now. The main experimental results are summarized as follows: 1 The results on the mice toxicology gene chip for the unprocessed and processed RPm The KM mice hepatotoxic model caused by the RPm at the different dosages was established in the present study. The results obtained show that the mouse average body weight obviously decreased in the groups at the different dosages of the unprocessed RPm: the 10 g/kg.d .group decreased 20%; 20 g/kg.d. group decreased 42%, and 50% mice died at 20 g/kg.d. group. The main experimental results on the mice toxicology gene chip The RPm is the CYP450 inhibitor. As compared with the processd RPm, the CYP3A4, CYP4A5 of the unprocessed RPm demonstrate the marked downregulation, which leads to the increase of the poison absorbtion into the body with the result that the unprocessed RPm yields the marked hepatotoxication. The hepatotoxication was produced because the following 6 pathways were affected: ①PPAR signaling pathway, the chief toxicity target genes are RXRB, CYP7a1, Acadl, Apoa2, Cyp4a, FABP2 and MAPKKK5 etc. ②Calcium signaling pathway, the chief toxicity target genes are CAMK2B, CACNA1F, S100A1, F2R, Ryr1,Slc8a2 and Camk4 etc. ③Neuroactive ligand-receptor interaction, the chief toxicity target genes are Chrm4, Ntsr2, GABRR1, GRIK3 and F2R etc. ④Wnt signaling pathway, the chief toxicity target genes are Daam2, Rac1 etc. ⑤Complement and coagulation cascades, the chief toxicity target genes are F2R, Serpina1b, Cfi and FGA etc. ⑥Oxidative phosphorylation, the chief toxicity target genes are Atp5e, NDUFA1 etc. The above experimental results, for the first time , demonstrate on the gene level that the unprocessed Rpm toxicity is far stronger than the processed RPm one, and the toxicity of the water decoction of the unprocessed RPm is greater than the one of its acetone extracts, which shows that the chief toxicity components of the RPm are probably not only the anthraquinones, for example, the emodin, but the complex compounds produced by the interaction between the emondin and the stilbene glucoside which is the largest component of the unprocessed RPm. The result is accordance with the above effect of the RPm on the hepatic drugenzyme. Aftter being processed, in fact, the content of the stibene glucoside in the RPm markedly decreases. 2. The results on the pharmacodynamic differences between the unprocessed and processed RPm The results obtained show that the effects of processing on RPm pharmacodynamic behaviour received in the Chinese Material Medica are correct. It is known to author that this is the first experimental result in the research materials now available. The chief results are as follows: For the treatment of the antidepressant, the curative effect of the processed RPm is far better than the one of the unprocessed RPm. By contrast with the above results, the hypoblycemic effect of the unprocessed RPm is better than the one of the processed RPm. 3. The results on the Chemical Composition The results obtained by using HPLC-DAD fingerprint and by the determination of effective component content show that the main chemical components in the RPm after being processed do not disappear, but their contents change. The contents of the stilbene glucoside (SG) and emodin in the different samples were determined as follows: SG contents 5.512 % for the unprocessed RPm 3.811 % for the processed RPm (Steamed) 3.588 % for the processed RPm (black soybean) Emodin contents 0.094 % for the unprocessed RPm 0.119 % for the processed RPm (Steamed) 0.126 % for the processed RPm (black soybean) The combination of above experimental results on the toxicity, the pharmacodynamics and the chemical composition indicates that the changes of the content ratio of SG/emodin may be the substance base of the toxicity decrease and pharmacodynamic changes of the RPM by the processing.