水蛭活性溶液脱腥脱色工艺研究

目的：采用不同方法对3种水蛭活性溶液进行脱腥脱色处理,评选出最优工艺方法。方法：采用羟丙基-β-环糊精、β-环糊精、粉末（颗粒）活性炭、高岭土、酵母粉为脱腥脱色材料研究了3种水蛭活性溶液的脱腥脱色工艺方法,并以感官评分、有效肽含量、物质活力单位为指标,得出最优脱腥脱色方法。结果：粉末活性炭-高岭土方法、酵母粉发酵方法的脱腥脱色效果良好,有效肽含量可以达到80%左右,活力基本不变,达到了脱腥脱色的目的。结论：粉末活性炭-高岭土方法、酵母粉发酵方法的脱腥脱色效果良好,为水蛭的后期开发利用奠定基础。     

基于网络药理学和分子对接法研究参七解郁方治疗双心疾病的分子机制

目的通过网络药理学与分子对接法研究参七解郁方治疗双心疾病的潜在有效成分和作用通路。方法通过中药系统药理学数据库分析平台 TCMSP和 TCMID数据库查找该方所用药物的活性成分以及作用靶标,在 Gene Cards数据库下载双心疾病靶点;以 String平台数据为基础,利用 Cytoscape软件构建参七解郁方与双心疾病共同靶点的蛋白质 -蛋白质相互作用网络( PPI);绘制“活性成分 -靶点 -通路”网络图;采用 Auto Dock Tools工具进一步对接药物活性成分及可能作用的靶点。结果参七解郁方有 89个主要活性成分, 56个主要靶点,与 30个信号通路有关。将度值大于5的前 7个活性成分的分子配体与前5个靶点进行分子对接,结果显示活性成分与靶点分子对接能力均较好。结论参七解郁方通过多成分、多靶点、多通路参与双心疾病的治疗。     

源于补肾中药及其复方的抗骨质疏松活性成分及机制的研究

目的对作者研究组多年来从补肾中药、药食两用药材及复方中寻找抗骨质疏松活性成分的研究结果进行总结,为进一步研究提供参考依据。方法应用成骨细胞、破骨细胞、PTH诱导的骨吸收培养系统筛选及活性追踪,应用动物体内实验确证活性部位。用各种化学手段分得活性成分,用细胞培养和E lisa的方法研究其作用机制。结果通过以上研究,得到了一系列抗骨质疏松活性成分,并为药食两用药材和临床验方的抗骨质疏松应用提供依据。     

基于网络药理学探讨固肾安胎方治疗先兆性流产的作用机制

目的:通过网络药理学方法探讨固肾安胎方治疗先兆性流产的作用机制.方法:运用TCMSP、SwissTarget等数据库筛选化学成分、获取潜在靶点,构建药材-成分-靶点网络图,并进行信号通路的富集与分析,利用分子对接技术探究潜在靶点与活性成分的相互作用.结果:获得固肾安胎方的核心成分89个和作用靶点34个,涉及Steroi...     

Evaluation of the analgesic and anti-inflammatory activities of some thiazolo[4,5-d]pyrimidines

Some thiazolo[4,5-d]pyrimidine-7(6H)-one derivatives were evaluated in vivo for their analgesic and anti-inflammatory activities. The results were compared with that of acetyl salicylic acid and phenylbutazone. Compounds 3b and 3h were the most active in the anti-inflammatory paw edema inhibition test. In terms of the analgesic activity (acetic acid writhing test), the most active compound was 2a followed by 31. The most active members of the series were investigated for their ED50 values and ulcerogenic potential.     

EFFECT OF GONADOTROPINS AND PREGNANCY ON PRORENIN AND RENIN IN THE RAT

1. Stimulation of adult female rats with pregnant mare serum gonadotropin (PMSG) and human chorion gonadotropin (hCG) increased active plasma renin about two-fold, but caused only a slight increase of plasma prorenin. The concentrations of active renin and prorenin in the ovaries, and active renin in the uterus all increased about two-fold 2 days after stimulation with PMSG. The prorenin in the uterus was below detection in unstimulated rats and did not change consistently after PMSG. 2. Active renin and prorenin in plasma were unchanged in relation to pregnancy, except for a slight decrease of prorenin in the third trimester. In the first and third trimester the concentration in the ovaries of active renin and prorenin was decreased to about one-third of that in normal female rats. In contrast active renin in the uterus was increased about two-fold in the first trimester, whereas prorenin did not change consistently. 3. Our results confirm that gonadotropins and pregnancy affect the renin-angiotensin system in rats. However, the changes in the plasma seem to be much smaller than those previously reported in humans. Accordingly, our results do not support a systemic role of prorenin for reproduction in the rat.     

Anticoccidial activity of crown polyethers

Anticoccidial activity in vitro against Eimeria tenella is reported for crown polyethers with ring sizes from 14 to 30 atoms. The most potent compounds, 4 and 9, were found active at 0.33 ppm, but none were active in vivo. Test results are discussed in terms of lipophilic shielding of complexed cations.     

Changes in plasma active renin and prorenin after endoscopic retrograde pancreatography

Plasma active renin, total renin (active renin plus prorenin) and immunoreactive trypsin were measured simultaneously before and after endoscopic retrograde pancreatography (ERP) in 9 subjects suspected of having pancreatic or biliary disease. After ERP, their plasma immunoreactive trypsin level increased significantly (p less than 0.02) from 12.4 +/- 1.5 to 163 +/- 57 ng/ml (means +/- SEM), while their plasma renin activity, total renin activity and ratio of active renin to total renin did not change. Individual values for the ratio of active renin to total renin correlated significantly (p less than 0.01) with those for immunoreactive trypsin in the basal condition (before ERP), but not after ERP. These results suggest that plasma trypsin is involved in activation of prorenin to active renin in the basal condition, and that ERP-induced increase in plasma trypsin has no effect on activation of prorenin.     

Alkylthiocolchicines and N-deacetyl-alkylthiocolchicines and their antileukemic activity.

A series of alkylthiocolchcines (methyl, ethyl, n-butyl, n-hexy, n-octyl, and pinanyl) was prepared from colchicine by treatment with the appropriate alkyl mercaptan and p-toluenesulfonic acid. Some of these compounds (methyl-, ethyl-, and n-butylthiocolchicines) were deacetylated in good yields with 2 N hydrochloric acid in methanol. These compounds were tested for their antileukemic activity in an in vitro assay against L-1210 (mouse leukemia). Preliminary results showed that methylthiocolchicine is more active and the other alkylthiocolchicines are much less active than colchicine. N-Deacetyl-methylthiocolchicine is as active as colchicine.     

Evaluation of antibacterial activity in experimental meningo-encephalitis in mice

Mice infected intracerebrally (ic) or intraperitoneally (ip) with Pseudomonas aeruginosa were treated subcutaneously with graded doses of five antibiotics all of which displayed anti-pseudomonal activity in vitro. The analysis of MIC, ED50 in the ip infection model (ED50-ip) and that in the ic system (ED50-ic) for each agent showed: gentamicin, the most active agent in vitro, was also active in vivo, with an ED50-ic nearly six-fold higher than ED50-ip; ceftazidime, considerably active both in vitro and in vivo, showed comparable values of ED50 in the two systems; ceftriaxone, also active in vitro, showed limited activity in vivo, its two ED50 values being similar; aztreonam, moderately active both in vitro and in vivo, showed comparable activity in the two infection models; carbenicillin, the least active agent in vitro, gave poor results in vivo, with an ED50-ic 2.6-fold higher than ED50-ip.     

Slow self-activation enhances the potency of viridin prodrugs

When the viridin wortmannin (Wm) is modified by reaction with certain nucleophiles at the C20 position, the compounds obtained exhibit an improved antiproliferative activity even though a covalent reaction between C20 and a lysine in the active site of PI3 kinase is essential to Wm's ability to inhibit this enzyme. Here we show that this improved potency results from an intramolecular attack by the C6 hydroxyl group that slowly converts these inactive prodrugs to the active species Wm over the 48 h duration of the antiproliferative assay. Our results provide a guide for selecting Wm-like compounds to maximize kinase inhibition with the variety of protocols used to assess the role of PI3 kinase in biological systems, or for achieving optimal therapeutic effects in vivo . In addition, the slow self-activation of WmC20 derivatives provides a mechanism that can be exploited to obtain kinase inhibitors endowed with physical and pharmacokinetic properties far different from man-made kinase inhibitors because they do not bind to kinase active sites.     

The impact of low levels of amorphous material (<5%) on the blending characteristics of a direct compression formulation.

During the manufacture of tablets for registration stability studies, it was observed that blends manufactured using milled active frequently failed the blend content uniformity criteria (actual relative standard deviation (RSD) of 4-15%) at the prelubrication stage, whereas unmilled active batches were consistently giving very good blend uniformity results (RSD<3.5%). The addition of magnesium stearate dramatically improved the blending characteristics of the milled batches, suggesting that milling had altered the surface properties. A hypothesis was presented that amorphous material was created during the milling of the active batches, which subsequently recrystallised over a short period of time e.g. days/hours. Following recrystallisation the batches did not exhibit the same physical properties as the unmilled actives, and this resulted in the drug product batches failing to meet their pre-lubrication acceptance criteria for blend content uniformity. This paper describes the results of a laboratory scale study to investigate this hypothesis and therefore explain the processing issues that were observed during the manufacture of the registration stability batches with milled active batches.     

乙型肝炎患者血清可溶性肿瘤坏死因子受体的检测及临床意义

应用酶联免疫吸附试验法测定了３０例慢性活动型肝炎及２４例慢性重型肝炎患者血清可溶性肿瘤坏死因子受体（ｓＴＮＦＲ）水平。结果显示：慢性理型肝炎及慢性活动型肝炎患者ｓＴＮＦＲ水平显著升高，尤发慢性重型肝炎患者为甚，升高程度与总胆红素呈正相关，与凝血酶原活动度呈负相关。对２４例慢性重型肝炎患者进一步分析表明：伴有感染或肝肾综合征时，ｓＴＮＦＲ水平显著高于无感染或肝肾综合征患者，最终死亡者其水平也显著高于     

Comparison of the effect of substituted benzamides on midbrain dopamine neurones after treatment of rats for 21 days

We have tested five different substituted benzamides (nemonapride, D,L-sulpiride, remoxipride, raclopride and zacopride) for their potential to decrease the number of spontaneously active dopamine neurones in the rat midbrain after treatment for 21 days. Nemonapride, D,L-sulpiride, and remoxipride significantly reduced the number of spontaneously active dopamine neurones in the ventral tegmental area, indicating an antipsychotic potential, while raclopride and zacopride induced but minor effects. The number of active dopamine neurones in the substantia nigra pars compacta was reduced by nemonapride at higher doses which should indicate the propensity for developing extrapyramidal side-effects. In conclusion, several of the substituted benzamides showed an antipsychotic profile in this test model. In addition, some of the benzamides also showed a propensity for extrapyramidal side-effects and these results are in accordance with the profile reported from clinical trials. However, the results obtained with this model indicate that raclopride neither has antipsychotic potential nor induces extrapyramidal side-effects. The reason for this discrepancy is at present not known.     

Natural Products: Effects of Sho-saiko-to Extract on Fibrosis and Regeneration of the Liver in Rats

Sho-saiko-to, one of the most widely used Chinese herbal preparations, has long been used for the treatment of chronic liver diseases. We have investigated its effect in retarding the process of liver fibrosis and accelerating liver regeneration, especially its effect on Ito cells that are thought to be deeply involved with liver fibrosis. Sho-saiko-to extract and its active constituents were orally administered to rats with dimethy lnitrosamine-induced liver-injury. After treatment with sho-saiko-to extract hepatic function improved, histopathological results confirmed repair of liver tissue, and retinoid levels increased. On the other hand, when active constituents of sho-saiko-to extract were administered alone, liver retinoid levels remained low, implying that interaction among active constituents of the extract was suppressing Ito cell activation. When sho-saiko-to extract was administered to 70% hepatectomized normal and liver-injured rats, liver weight, the number of S-phase-cells and retinoid levels increased with time. However, these changes were different for normal and liver-injured rats, suggesting that the site of action of sho-saiko-to extract in regenerating liver is different for normal and liver-injured rats. These results show that sho-saiko-to extract was useful for suppressing the activation of Ito cells.     

The relative purgative activities of 1,8-dihydroxyanthracene derivatives

The purgative activities of twelve different 1,8-dihydroxyanthracene derivatives including free anthraquinone, anthrone and dianthrone forms, anthraquinone O-glycosides and dianthrone O-glycosides were compared with senna pod powder using the production of wet faeces by mice as a criterion of purgation. The higher purgative activity of the dianthrone glycosides was confirmed for the compounds based on rhein. Sennidin (rhein dianthrone) was more active than had previously been reported. These highly active compounds had parallel dose response curves which were not parallel to those of the less active rhein anthrone, rhein, aloe-emodin and chrysophanol. Emodin and chrysazin were inactive in mice. The highly active compounds exerted a high activity during the initial 3 h after dosage while the less active compounds were virtually inactive during this period. Rhein anthrone appeared to act initially like the highly active primary sennosides, sennoside A and sennidin and later as the less active rhein. The results are discussed in relation to the mode of action of orally administered 1,8-dihydroxyanthracene derivatives.     

一株具有抗肿瘤活性的土壤放线菌的筛选与菌种鉴定

目的快速高效的筛选到有抗肿瘤活性的土壤放线菌。方法初筛采用MTT法检测样品作用后A549细胞、HGC-27细胞和正常对照细胞N9的成活率,PI染色流式细胞检测技术复筛可能致细胞凋亡的菌株,以及对活性菌株进行种属鉴定。结果与结论从350株土壤放线菌中初筛得到16株菌种,它们的代谢产物对A549及HGC-27细胞有抑制作用,但对N9细胞生长无影响;复筛得到1株编号为1070的菌株的代谢产物能使A549细胞经过处理后,经流式细胞仪检测到亚二倍体峰,峰高为32.07%。从菌株菌落形态、孢子丝形态、生理生化特性及16SrDNA序列、系统进化分析鉴定该菌种为Streptomyces capillispiralis。     

The mechanism of the rearrangement of 1-benzyl-1,2-dihydroisoquinolines (author's transl)

The Mechanism of the Rearrangement of 1-Benzyl-1,2-dihydroisoquinolines Based on new findings on the dependence of the rearrangement on external parameters, in agreement with earlier results, a bimolecular cyclic synchronous mechanism is formulated as a possible pathway for the rearrangement. This mechanism is supported by the reaction of the optically active acetal 6 , which gives the optically active rearrangement product 9 .     

Evaluation of false positive rate based on exposure–response analyses for two compounds in fixed-dose combination products

We explored the type I error rate (false positive rate) associated with exposure–response (ER) analyses for two compounds in a fixed-dose combination product through simulations. In the simulations, at least one compound was assumed to be inactive, whereas the active compound followed E_max model at different concentration ranges. The simulated data were independently evaluated by pre-specified univariate or multivariate linear, log-linear models, and mixed linear log-linear models. The type I error rate was evaluated by comparing the total number of falsely identified significant slope estimates with the total number of models with successful convergence. We demonstrated that ER analyses results based on data from fixed-dose combination products at various dose levels should be interpreted with caution. A univariate analysis, even though is appropriate to guide dose selection, is inadequate to identify the active compound. Multivariate analyses can be applied to determine the active compound only when the underlying ER relationship for each compound (especially for the active compound) has been adequately defined or approximated. The false positive rate in determining a significant ER relationship is elevated, when the underlying ER relationship (especially for the active compound) is erroneously or inadequately defined. Without the assurance of the correct structural models, the identified significant ER relationship does not necessarily indicate that the compound associated with the significant slope estimate is pharmacologically active.