By using the pharmacophore model of mineralocorticoid receptor antagonists as a starting point, the experiment stud- ies the method of traditional Chinese medicine formula design for anti-hypertensive. Pharmacophore models were generated by 3D-QSAR pharmacophore (Hypogen) program of the DS3.5, based on the training set composed of 33 mineralocorticoid receptor antagonists. The best pharmacophore model consisted of two Hydrogen-bond acceptors, three Hydrophobic and four excluded volumes. Its correlation coefficient of training set and test set, N, and CAI value were 0.9534, 0.6748, 2.878, and 1.119. According to the database screening, 1700 active compounds from 86 source plant were obtained. Because of lacking of available anti-hypertensive medi cation strategy in traditional theory, this article takes advantage of patent retrieval in world traditional medicine patent database, in order to design drug formula. Finally, two formulae was obtained for antihypertensive.
Antihypertensive Agents ; chemistry ; pharmacology ; Databases, Factual ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Medicine, Chinese Traditional ; methods ; Mineralocorticoid Receptor Antagonists ; chemistry ; pharmacology ; Models, Molecular

To study the quantitative structure-activity relationship (QSAR) between the stuctures of 29 flavonoids and the inhibitory activity of their multidrug resistance-associated protein (MRP) 1 and 2 by using the comparative molecular similarity index analysis (CoMSIA). By studying the impact of the combination of different molecular force fields, researchers obtained the molecular force fields that played an important role in inhibiting the activity of MRP1 and MRP2, built the optimized QSAR model, and discussed the structural modification method for flavonoids' multidrug resistance-associated protein inhibitor. The results of the study could not only provide the guidance for new drug R&D, but also help partially discuss the synergy mechanism between MRP1 and MRP2 receptors and traditional Chinese medicines containing flavonoids.
Drugs, Chinese Herbal ; chemistry ; pharmacology ; Flavonoids ; chemistry ; pharmacology ; Humans ; Models, Molecular ; Multidrug Resistance-Associated Proteins ; antagonists & inhibitors ; chemistry ; Quantitative Structure-Activity Relationship

Nicotinic acid could increase high density lipoprotein and reduce serum total cholesterol, low density lipoprotein cholesterol and triglycerides in human bodies, thus is frequently applied in treating low high-density lipoprotein cholesterol and hypertriglyceridemia in clinic. However, according to the findings, nicotinic acid could also cause adverse effects, such as skin flush, beside its curative effects. In this study, bioisosterism, fragment-based search and Lipinski's Rule of Five were used to preliminarily screen out potential TCM ingredients that may have similar pharmacological effects with nicotinic acid from Traditional Chinese medicine database (TCMD). Afterwards, homology modeling and flexible docking were used to further screen out potential nicotinic acid receptor agonists. As a result, eleven candidate compounds were derived from eight commonly used traditional Chinese medicines. Specifically, all of the candidate compounds' interaction with nicotinic acid receptor was similar to nicotinic acid, and their docking scores were all higher than that of nicotinic acid, but their druggability remained to be further studied. Some of the eight source traditional Chinese medicines were used to lower lipid according to literature studies, implying that they may show effect through above means. In summary, this study provides basis and reference for extracting new nicotinic acid receptor agonists from traditional Chinese medicines and improving the medication status of hyperlipidemia.
Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; chemistry ; Humans ; Models, Molecular ; Molecular Structure ; Nicotinic Acids ; chemistry ; Nicotinic Agonists ; chemistry ; Protein Binding ; Receptors, G-Protein-Coupled ; agonists ; chemistry ; Receptors, Nicotinic ; chemistry

BACKGROUND: Gene therapy is a popular topic in domestic and overseas studies on biological therapy for brain tumor.OBJECTIVE: By using a newly constructed eukaryotic expression vector of pCR3-TK, the effect of the HSV-TK/ACV system on the proliferative activity of human glioma cells was investigated.DESIGN: Experimental study based on cells.SETTING: Department of neurosurgery and department of oncology in a university hospital.MATERIALS: The study was conducted at the National Key Laboratory of Veterinary Biotechnology of Harbin Veterinary Research Institute from January to April in 2004. The eukaryotic expression vector of pCR3-TK was constructed by the author. The TJ905 strain was a gift from professor Pu Pei-yu, who worked in the Neurology Institute of Tianjin city. The nontransfected cells and the cells transfected with pCR3-Uni vector were set as controls.METHODS: By using Lipofectamine(a cationic liposome), the pCR3-Uni vector and the recombinant pCR3-TK plasmid(inserted with HSV-TK gene)were transfected into the human glioma cell strain-TJ905. Then the positive clones were picked out and were given ACV(50 mg/L) . Totally 72 hours later, the cover slips were collected and silver staining for nucleolus organizer regions(AgNORs) was performed.MAIN OUTCOME MEASURES: After the ACV treatment and AgNORs staining, the numbers of silver-stained granules in TJ905 cells with or without transfections were counted respectively.RESULTS: In those cells transfected with HSV-TK gene, after ACV treatment, a significant decreasing in proliferative activity could be observed, and the average numbers of the silver-stained granules in cells transfected with pCR3-Uni or pCR3-TK were 14.33 and 6.67 respectively( P ＜ 0.01).CONCLUSION: As an easy-to-operate method, AgNOR counting is helpful for the studies on the proliferative activity of cells and the investigations into the potential anti-tumor mechanism of the HSV-TK/ACV system.

Objective:To study the anti-inflammatory and analgesic effects of the volatile oil from Piper puberulum ( Benth. ) Max-im. in Guizhou. Methods:Fifty KM mice were randomly divided into five groups (10 ones in each), the model control group (sa-line), low concentration volatile oil group (0. 125 ml/100 ml), medium concentration volatile oil group (0. 25 ml/100ml), high con-centration volatile oil group (0. 5 ml/100 ml) and aspirin group (3 mg·ml-1). Mouse ear swelling induced by xylene and skin capil-lary permeability were used to evaluate anti-inflammatory activity of the volatile oil from Piper puberulum ( Benth. ) Maxim. in Guizhou. Acetic acid-induced abdominal eonstrietion test and hot-plate test were applied to evaluate anti-analgesic activity of the vola-tile oil from Piper puberulum ( Benth. ) Maxim. In Guizhou. Results:Compared with that in the model group, the mouse ear swelling in the medium concentration volatile oil group, high concentration volatile oil group and aspirin group was significantly reduced ( P<0. 05). The skin capillary permeability in the high concentration volatile oil group and aspirin group was significantly reduced (P<0. 05 or P<0. 01). Compared with that in the model group, the writhing times in the medium concentration volatile oil group, high concentration volatile oil group and aspirin group were significantly reduced (P<0. 05 or P<0. 01). The pain threshold in the high concentration volatile oil group was effectively reduced (P<0. 05 or P<0. 01). Conclusion: The volatile oil from Piper puberulum ( Benth. ) Maxim. in Guizhou has promising anti-inflammatory and analgesic activities.

The amounts of iron and amino acids in dried pig powder were determined. It contained a large quantity of iron (230-260m/100g) and all essential amino acids. The blood fortified wheat flour biscuit containing 15mg Fe/100g was made and 30?2g of the biscuit was given to 65 primary school students (age 8-10) per capita per day during school day break for 40 days from Sep to Oct in 1984. For the control group, equal amount of the same biscuit without blood fortification was given to 34 subjects of the same age. Finger blood was taken for determination of hemoglobin, hematocrit, RBC count and serum ferritin before and after the experiment.there were significant differences (P

ObjectiveTo study the effect of heat stress on the cytoskeleton and cell cycle of human umbilical vein endothelial cell (HUVEC) in vitro.Methods HUVEC was cultured in vitro in 5%CO2 medium at 37℃ (control group) or 43℃ (heat stress group) for 1 hour. Coomassie brilliant blue R-250 staining was used to determine the effect of heat stress on the cytoskeleton. The cells in heat stress group were subsequently cultured at 37℃in 5%CO2 medium after heat stress for 1 hour, and cell cycle of HUVEC was determined at 0, 6, 12, 18 and 24 hours with flow cytometry.Results Under light microscopy normal cytoskeleton was observed in control group, but thicker and shorter cytoskeleton was found after a rise of temperature, and stress fibers were found in heat stress group. The DNA content of HUVEC at all time points in G0/G1 stage was 38.07%-55.19% after heat stress. The DNA content in control group was 48.57%, and it was 54.06%, 55.19%, 48.23%, 38.07%, and 41.03% at 0, 6, 12, 18, 24 hours in G0/G1 stage in heat stress group. DNA content in S phase was 35.33%-48.18%. The DNA content in control group was 44.62%, and it was 35.33%, 39.50%, 42.50%, 48.18%, and 47.99% at 0, 6, 12, 18, 24 hours in S stage in heat stress group. DNA content in G2/M phase was 5.31%-13.75%. The DNA content in control group was 6.81, and it was 10.61%, 5.31%, 9.27%,13.75%, and 10.98% at 0, 6, 12, 18, 24 hours in G2/M stage in heat stress group. It was demonstrated that compared with control group, the DNA content in G0/G1 stage was significantly increased when the HUVEC were separated from heat stress within 6 hours, and it recovered at a similar level as control group at 12 hours.Conclusion Heat stress can change the cytoskeleton of HUVEC, and cause stagnation at G0/G1 stage in cell cycle.

Objective:To evaluate the effect of continuing intervention on prophylactic application of antibiotics in sterile operation in urology department by clinical pharmacist to provide reference for the clinical prophylactic application of antibiotics. Methods:All cases of discharged patients underwent sterile operation in urology department of our hospital from July 2010 to June 2014 were divided into three groups according to the intervention time and methods: non-intervention group(n=141), stage Ⅰ intervention group(n=139), stage Ⅱ intervention group (n=162) and stage Ⅲ intervention group (n=137). The prophylactic application of antibiotics was statistically analyzed. Results:After the continuing intervention, the prophylactic application rate of antibiotics in the three inter-vention groups was decreased significantly from 100% before the intervention respectively to 34. 5%,18. 5% and 14. 6% after the in-tervention (P<0. 01). The rationality rate of prophylactic application was improved significantly from 36. 9% before the intervention respectively to 58. 3%, 63. 3% and 85. 0% after the intervention (P<0. 01). The course of prophylactic application was decreased significantly from (138.2 ±31.6)h respectively to (89.9 ±48.0)h,(72.8 ±32.5)h and(45.1 ±29.5)h (P<0.01) and the post-operative infection rate was decreased from 2. 8% respectively to 2. 1%,1. 8% and 1. 4%. Conclusion:The pharmaceutical interven-tion is feasible and valid to improve the rational prophylactic use of antibiotics in urological surgery.

Objective To investigate the relationship between insulin resistance and erythrocyte in- sulin receptors in patients with gout associated with macroalbruminuria(MAU).Methods FBG,PBG,FINS, P2hINS,CH,TG,HDL,LDL-c,UA and erythrocyte insulin receptors were determined in 44 patients with MAU,62 patients with normal MAU(NMAU).Results In MAU,the levels of FINS,TG,LDL-c and HOMA-IR were(16?4)mU/L,(2.5?0.6)retool/L,(3.2?0.5)mmol/L and 3.6~1.2 respectively.While they were(13?3) mU/L,(2.3?0.8)mmol/L,(3.0?0.5)mmol/L and 3.0~0.4 in NMAU group.The levels of FINS,TG,LDL-c and HOMA-IR were significantly higher in the MAU patients than those in NMAU patients(P

BackgroundPosterior capsule opacification(PCO) is the main cause inducing low vision after extacapsular cataract extraction. Our previous study determined that polylysine-ethylene diamine tetraacetic acid (EDTA) (PLE) can suppress the incidence of PCO. ObjectiveThe goal of this experiment was to investigate the inhibition of polylysine-EDTA on rabbit lens epithelial cells (LECs)proliferation in vitro and the effective concentrations of polylysine-EDTA. MethodsThe anterior capsular membranes from 10 3-month-old clean New Zealand white rabbits were digested and then cultured to obtain the LECs. The second and third generation of LECs were inoculated on the 96-hole culture plate with the cell density of the 1 × 105/ml. 12.5,25.0,50. 0,100. 0 μmol/Lof PLE were added into the culture medium for 48 hours respectively,and the DMSO medium was used at the same way as the control group. The proliferation of the LECs was then detected by MTT method and the inhibitory rate of PLE on LECs growth was calculated. ResultsLECs grew at a near normal state in ≤25.0 μmol/L PLE groups,however,cultured LECs were out of shape and the numbers decreased with the weakened adhesion ability in ≥50.0 μ mol/L PLE groups. The A490 values of LECs were 0. 278±0. 013,0. 266±0. 028,0. 260±0. 022 and 0. 247±0. 012 in 12. 5,25.0,50. 0, 100. 0 μmol/L polylysine-EDTA groups respectively and were lower than 0. 311 ±0. 038 of DMSO control group( P=0. 035,0. 011,0. 009,0.013 ). The inhibitory rates of 12. 5,25.0,50. 0, 100.0 μmoL/L PLE on LECs proliferation were 10.61％ , 14.47％ , 16.40％ and 20. 58％ respectively. ConclusionsPolylysine-EDTA can inhibit the growth and proliferation of LECs in vitro at a dose-dependent manner.