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

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 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.

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

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.

OBJECTIVETo observe the effect of IPS-B2 on mouse peritoneal macrophages and the transcription of IL-1beta, IL-6, TNF-alpha and iNOS.

METHODELISA method and Griess method were used to detect the effect of mouse peritoneal macrophages produce cytokines IL-1beta, IL-6, TNF-alpha and cytotoxic effectors NO. The transcription of IL-1beta, IL-6, TNF-alpha and iNOS was detected by real-time RT-PCR method.

RESULTIPS-B2 could not promote mouse peritoneal macrophage production, but it could significantly improve the IL-1beta, IL-6, TNF-alpha content in mouse peritoneal macrophages culture supernatant, and increase the gene expression of IL-1beta, IL-6, TNF-alpha and iNOS.

CONCLUSIONIPS-B2 can enhance the ability of peritoneal macrophages to excrete bioactive substances and promote the transcription of bioactive substances to antitumor.

Agaricales ; chemistry ; Animals ; Gene Expression Regulation ; drug effects ; Interleukin-1beta ; biosynthesis ; genetics ; Interleukin-6 ; biosynthesis ; genetics ; Macrophages, Peritoneal ; drug effects ; metabolism ; Mice ; Nitric Oxide ; biosynthesis ; Nitric Oxide Synthase Type II ; metabolism ; Polymerase Chain Reaction ; Polysaccharides ; pharmacology ; RNA, Messenger ; biosynthesis ; Transcription, Genetic ; drug effects ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics

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

OBJECTIVET o summarize the clinical effects of the repairing methods for skin and soft tissue defection of heel.

METHODSFrom June 1998 to June 2009,42 patients with skin and soft tissue defection of heel underwent the repairing treatment,including 23 males and 19 females, with an average age of 37 years old ranging from 18 to 65. The causes of injuries included mangled injury in 22 cases, high fall injury in 10 cases, cut injury in 5 cases,melanoma in 3 cases, decubital ulcer in 2 cases. Of the 42 cases, 27 were on left side and 15 on right side. The defect area of skin ranged from 3 cm x 2 cm to 18 cm x 16 cm. The time between the injury and surgery ranged from 8 hours to 10 years. The wounds were repaired separately by medial plantar flap in 13 cases, lesser saphenous sural nerve vascular island flap in 18 cases, saphenous neurocutaneous vascular flap in 11 cases. The patients' outcome were evaluated with appearance,blood supply, texture, resilience and two points discrimination of the flaps.

RESULTSAll of the 42 flaps were survived. The distal skin necrosis occurred in 2 flaps, but healing occurred after debridement and intermediate thickness skin grafting. Three patients with sinus formation healed after 5 to 12 months of dressing change. All patients were follow-up for 8 months to 6 years. The flaps of all patients gained a satisfied shape after operation. The patients had a normal gait, the flaps had a good sense and a resistance to wearing,and no ulcer occurred. The two point discrimination of the flap was 4 to 12 mm.

CONCLUSIONIt is convenient and effective to repair the heel skin and soft tissue defects using medial plantar island skin flap when the defects is less then 8 cmx6 cm. As reliable blood supply,major artery preservation and high survival, the lesser saphenous sural nerve vascular island flap and saphenous neurocutaneous vascular flap can be transferred to repair the large soft tissue defect of heel.

Adolescent ; Adult ; Aged ; Female ; Foot Injuries ; surgery ; Heel ; abnormalities ; surgery ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; Soft Tissue Injuries ; surgery ; Surgical Flaps ; Young Adult