0.05).The gene frequencies of ACG-T235M and ACE-DD plus AGT-TT were significantly higher in the patients with CAD than in the controls respectively(all P

Combining the structural features of picotamide and linotroban, a series of N,N'-bis-(halogenophenyl)-4-methoxybenzene-1, 3-disulfonamides were designed and synthesized on the basic principles of drug design. The structures of target compounds were confirmed by IR, 1H NMR and HR-MS, and the in vitro antiplatelet aggregation activity was evaluated by Born turbidimetric method with adenosine diphosphate (ADP) as the platelet aggregation inducers. The assay results showed that twelve compounds (4b, 4f, 4l, 5b, 5d-5g, 5j, 5k, 5m and 5n) were found to have superior anti-platelet aggregation activities than the positive drug picotamide. The preliminary structure-activity relationship (SAR) has been explored.
Adenosine Diphosphate ; Drug Design ; Phthalic Acids ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; chemical synthesis ; chemistry ; Structure-Activity Relationship ; Sulfonamides ; chemical synthesis ; chemistry

Objective To establish the HPLC characteristic chromatogram of Shenshitong Granules. Methods The chromatographie fingerprints were obtained through Thermo Hypersil GOLD-C18 column (4.6 mm×250 mm, 5μm) with the gradient elution solvent system composed of acetonitrile-0.2% phosphoric acid (0-20 min, 5%→10% acetonitrile;20-40 min, 10%→12%acetonitrile;40-60 min, 12%→14%acetonitrile;60-90 min, 14%→20%acetonitrile;90-120 min, 20%→28%acetonitrile). The detective wavelength was set at 280 nm;the flow rate was 1.0 mL/min;the column temperature was maintained at 30 ℃;the analysis time was 120 min. Results The HPLC characteristic chromatogram was built on basis of 10 batches of Shenshitong Granules, including 27 common peaks which contain the characteristic peaks of 6 Chinese herbal medicines, such as Radix Salvia Miltiorrhizae, Herba Lysimachiae, etc. Conclusion The established HPLC fingerprint has high sensitivity and good repeatability, and can be available for quality evaluation of Shenshitong Granules.

Combining the structural features of picotamide and linotroban, a series of N,N'-bis-(halogenophenyl)-4-methoxybenzene-1, 3-disulfonamides were designed and synthesized on the basic principles of drug design. The structures of target compounds were confirmed by IR, 1H NMR and HR-MS, and the in vitro antiplatelet aggregation activity was evaluated by Born turbidimetric method with adenosine diphosphate (ADP) as the platelet aggregation inducers. The assay results showed that twelve compounds (4b, 4f, 4l, 5b, 5d-5g, 5j, 5k, 5m and 5n) were found to have superior anti-platelet aggregation activities than the positive drug picotamide. The preliminary structure-activity relationship (SAR) has been explored.

Objective To observe the effects of electro-acupuncture (EA) at “Weizhong” (BL40) on expressions of Fas and FasL in rat models with lumbar disc degeneration; To discuss its mechanism of action.MethodsThirty SD rats were randomly divided into sham-operationgroup, model group and EA group, with 10 rats in each group. The sham-operation group was treated with sham operation to incide local skin; the model and EA groups established rat model of lumbar disc degeneration by puncturing the annulus fibrosus. Four weeks after modeling, rats in the sham-operation and model groups received fixed treatment under identical condition, and rats in the EA group were treated with EA at “Weizhong” (BL40) in 20 minutes, once a day, for 4 weeks. After treatment, Western blot and RT-PCR technology were used to test the protein and mRNA expression levels of Fas and FasL.ResultsThe expressions of Fas and FasL in the model group were higher than those in the sham-operation group (P<0.05); protein and mRNA expression levels of Fas and FasL in the EA group were lower than those in the model group (P<0.05). ConclusionEA at “Weizhong” (BL40) can reduce the expressions of Fas and FasL to inhibit the development of lumbar disc degeneration.

Objective To establish a pre -column derivatization and HPLC method for the determination of free amino acids in serum and urine with phenyl isothiocyanate ( PITC ) as derivatization reagent . Methods The determination was performed on waters e 2695 sys-tem.Sample was separated by Shim -pack VP-ODS column(250 mm × 4.6 mm,5 μm ) with a gradient elution of mobile phases composed of methanol/acetate/H2 O( pH 6.5 ) , the content of amino acid were tested by UV at 254 nm.Results The developed method had a good linear ( r>0.991 8 ) in the content range of 2-200 μg· mL-1 , with an aver-age recovery ranged from 88.5% to 123.4%.The precision was within 0.12%-3.42%.Conclusion PITC pre-column derivatization and HPLC method was developed and validated , which had good accuracy , suitable for the determination amino acid in serum and urine of patients with diabetes .

Objective To investigate the medical care conducts of community residents of Dongying and analyze the main problem in order to provide the evidence for optimizing the community health service model.Methods Stratified cluster sampling method was used,and 330 community residents in 4 communities were investigated with questionnaire about the medical care conducts.Results Among 330 residents,63％ of them did not attend medical clinics after getting minor illnesses,only 12.7％ of them chose to check up in large hospitals,and 14.2％ went to the community services.However,there were 10.1％ of the population attended private clinics.These medical care conducts were significantly related to gender,age,education level,and the payment patterns (x2 =51.0,106.5,16.3,31.8;P ＜0.05).Health condition has no effect on the residents' medical care conducts (x2 =11.3;P ＞ 0.05 ). Residents with different ages had significantly different influencing factors of choosing medical institution,and different their satisfaction on community service center ( x2 =15.7,44.7 ;P ＜ 0.01 ).Conclusions It should be encouraged to integrate the medical resources in order to establish the effective community services.The charge standards of medical procedures should be restricted by authority policies,and the residents should be guided to attend clinics in an appropriate way with reasonable payment.

Objective To investigate the vitamin D (VD) level and determinants among young children aged 6 to 23 months in 4 poverty-stricken ethnic minority areas of Yunnan Province. Methods Multistage stratified cluster sampling method was used. 1 255 young children aged 6-23 months from 3 to 4 towns of Jianchuan County, Yiliang County, Mojiang County and Lushui County. Questionnaires on caregivers, physical and serum 25(OH)D measure were achieved. VD level and influencing factors were described and analyzed. Results Overall VD level was 20.6(16.3,25.4) ng/ml. The proportion of VD deficiency, VD insufficiency and VD sufficiency were 7.1%, 39.2% and 53.7% respectively. The risk of VD insufficiency elevated with children’age increasing or no VD supplement (P<0.05). Hani minority can decrease the risk of VD deficiency and insufficiency (all P<0.05). Thus, the risk of VD deficiency and insufficiency in children of female, Lisu or Bai minority, or in children who had no nutritional package supplement would increase (all P<0.05). Conclusions The VD level of children aged 6-23 months in poverty-stricken ethnic minority areas of Yunnan Province was low. VD insufficiency was dominating. The intervention of VD deficiency and insufficiency may focus on the children of female, Lisu minority, Bai minority or older than 18 months. This study highlight that enhancing caregivers’ knowledge of VD nutrition, adding VD and nutritional package supplement actively are beneficial to improve VD nutrition of young children in minority poverty areas of Yunnan.

The paper is to report the pharmacokinetic character of a series of chemical compounds in vitro and in vivo. Metabolism stability of a series of chemical compounds was screened by using rat liver microsomes. The samples of different chemical compounds were combined and then simultaneously detected by LC-MS/MS. Compounds y13, y12 and y11 were screened out by microstability assay in vitro. The pharmacokinetics of compounds y11, y12 and y13 was evaluated by using SD rat. The plasma samples were pooled at the same time. The plasma concentrations were determined by LC-MS/MS. The pharmacokinetic character of two compounds y13, y11 was good by screening in vivo, so they were developed for further research. High-throughput screening of drug candidates in vitro and in vivo was effective, to provide information for the chemical structure information and lower the drug development risk.
Animals ; Chromatography, Liquid ; methods ; Drug Evaluation, Preclinical ; methods ; Female ; High-Throughput Screening Assays ; methods ; Male ; Microsomes, Liver ; metabolism ; Pharmaceutical Preparations ; administration & dosage ; blood ; metabolism ; Pharmacokinetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; methods

OBJECTIVETo investigate the effects of endothelial microvesicles (EMVs) induced by calcium ionophore A23187 on H9c2 cardiomyocytes.

METHODSHuman umbilical vein endothelial cells (HUVECs) were treated with 10 micromol/L A23187 for 30 min. EMVs from HUVECs were isolated by ultracentrifugation from the conditioned culture medium. EMVs were characterized using 1 and 2 microm latex beads and anti-PE-CD144 antibody by flow cytometry. For functional research, EMVs at different concentrations were cocultured with H9c2 cardiomyocytes for 6 h. Cell viability of H9c2 cells and the activity of LDH leaked from H9c2 cells were tested by colorimetry. Moreover, apoptosis of H9c2 cells was observed through Hoechst 33258 staining and tested by FITC-Annexin V/PI double staining.

RESULTSEMVs were induced by A23187 on HUVECs, and isolated by ultracentrifugation. We identified the membrane vesicles (< 1 microm) induced by A23187 were CD144 positive. In addition, the EMVs could significantly reduce the viability of H9c2 cells, and increase LDH leakage from H9c2 cells in a dose dependent manner (P < 0.05). Condensed nuclei could be observed with the increasing concentrations of EMVs through Hoechst 33258 staining. Furthermore, increased apoptosis rates of H9c2 cells could be assessed through FITC-Annexin V/PI double staining by flow cytometry.

CONCLUSIONMicrovesicles could be released from HUVECs after induced by A23187 through calcium influx, and these EMVs exerted a pro-apoptotic effect on H9c2 cells by induction of apoptosis.

Annexin A5 ; Apoptosis ; Calcimycin ; pharmacology ; Calcium ; metabolism ; Cell Line ; Cell Membrane ; drug effects ; Coculture Techniques ; Flow Cytometry ; Fluorescein-5-isothiocyanate ; analogs & derivatives ; Human Umbilical Vein Endothelial Cells ; Humans ; Myocytes, Cardiac ; drug effects ; Staining and Labeling