Ebola virus, the cause of severe and fatal hemorrahagic fever in humans, belongs to filovirus family. This study was designed to establish a cell-based screening and evaluation system in the pharmacological study of antivirus compounds. Three reporter systems were established with recombinant pseudoviral luciferase of HIV core (pNL4-3.Luc.R(-)E(-)) packed with filovirus glycoprotein (EBOV-Zaire GP/HIV-luc, EBOV-Sudan GP/HIV-luc and Marburg GP/HIV-luc), which are required for virus entry of cells. The level of filovirus entry was determined by the expression of luciferase reporter gene in the infected cells. For screening of filovirus entry inhibitors, the vesicular stomatitis G packed pseudovirions (VSVG/HIV-luc) was used to determine the compound specificity. The results of known filovirus entry inhibitors demonstrated successful establishment of the new model systems, which would be useful in high throughput screening of anti-filovirus drugs in the future.
Antiviral Agents ; pharmacology ; Drug Evaluation, Preclinical ; methods ; Ebolavirus ; drug effects ; physiology ; Genes, Reporter ; Glycoproteins ; genetics ; Hemorrhagic Fever, Ebola ; Humans ; Luciferases ; Viral Proteins ; genetics ; Virus Internalization ; drug effects

OBJECTIVE:To promote the rational drug use in our hospital.METHODS:The in-patient and out-patient drug use in our hospital was monitored and analyzed.RESULTS:The income from pharmaceuticals accounted for 38% of the total income in our hospital and the drug use tend to be more rational after the practice of dynamic monitoring on drug use.CONCLUSION:Dynamic monitoring on drug use played a positive role on the rational use of drugs meanwhile it brings the proportion of drug consumption under effective control.

OBJECTIVE:To determine the dissolution of puerarin and 2,3,5,4'-tetrahydroxy-stibene-2-O-?-D-glycoside in Xinnaokang capsules.METHODS:The contents of puerarin and 2,3,5,4'-tetrahydroxy-stibene-2-O-?-D-glycoside were determined by HPLC and the dissolution rates of puerarin and 2,3,5,4'-tetrahydroxy-stibene-2-O-?-D-glycoside in Xinnaokang capsules were determined by basket-rolling method.RESUTLS:With water as releasing media,at a rotation rate of 100 r?min-1,the dissolution rate at 45 min was above 75% of the labeled amount.CONCLUSION:The method can be used for evaluation and control of the internal quality of Xinnaokang capsules.

9.0 mmol/L, and well controlled group if FPG0.05). However, in each group, the incidence rate of different algesic severity decreased with the increasing algesic severity. Conclusion EIP will occur in DM patients within a week after RCT. Well controlling of the blood glucose can reduce the incidence rate of EIP.

Background Scarring of the filtering bleb is a main cause of filtering surgical failure in glaucoma.It has been reposed that tetrandrine could suppress the proliferation of cultured human fibroblast of Tenons capsule in vitro and thus has the potential effect to prevent scarring after the filtering surgery. Objective Present study was to investigate the anti-cicatricial effect of tetrandrine drug delivery system(Tet DDS)during filtration surgery. Methods Filtration surgery was performed in bilateral eyes of 18 New Zealand white rabbits.The Tet DDS with 0.3 mg Tet,0.2 mg Tet or free-Tet were implanted subcunjunctially during the surgery.The filtering blebs were scored in 1 day,4,7,10,14 days after referring to the corneal thickness and bleb range under the slit-lamp biomicroscopy.The morphology of filtering bleb was assessed by in vivo confocal microscopy in 7 and 14 days after operation.The filtering bleb specimen was prepared in 7 and 14 days for the histopathological examination. Results The filtering bleb scores in Tet DDS implantation groups were significantly higher than those in free-Tet DDS group from 4 days through 14 days after trabeculectomy(P＜0.01),and the scores showed a considerably increase in 0.3 mg Tet DDS group compared with 0.2 mg Tet DDS group from 7 days through 14 days after trabeculectomy(P＜0.05).The filtering blebs of Tet DDS implantation groups were found with distinct subepithelial cystic spaces under the light microscopy and in vivo confocal microscopy on the 7th day and 14th day after surgery.Compared with free-Tet DDS group,the numbers of subepithelial mierocysts were much more(P＜0.01)and the area of microcysts was larger(P＜0.01)in Tet DDS group.The filtering tissue presented with more subepithelial microcysts and larger microcysts range in 0.3 mg Tet DDS group than 0.2 mg Tet DDS group in 7 and 14 days after operation(P＜0.05).The inflammatory cell infiltration wag milder in 0.3 mg Tet DDS group in comparison with 0.2 mg Tet DDS group and free-Ted DDS group.Conclusion Tet DDS has strong inhibitory effects on inflammatory cells activity and fibroblagt activity the early stage after filtering surgery and therefore improve the surgery success rate.

This study was designed to discover filovirus entry inhibitors in a drug library of commercial medicines. One thousand and six hundred drugs were screened using the ZEBOV-GP/HIV model, a pseudovirus formed by an HIV-core packed with the Zaire Ebola virus glycoprotein. We identified 12 gonadal hormone drugs with inhibitory activities in ZEBOV-GP/HIV entry at final concentration of 10 μmol x L(-1). Among them, three drugs exhibited strong activities with IC50 < 1 μmol x L(-1), such as toremifene citrate (IC50: 0.19 ± 0.02 μmol x L(-1)), tamoxifen citrate (IC50: 0.32 ± 0.01 μmol x L(-1)) and clomiphene citrate (IC50: 0.53 ± 0.02 μmol x L(-1)); seven drugs had moderate activities with IC50 between 1 and 10 μmol x L(-1), such as estradiol benzoate (IC50: 1.83 ± 5.69 μmol x L(-1)), raloxifene hydrochloride (IC50: 3.48 ± 0.07 μmol x L(-1)), equilin (IC50: 4.00 ± 9.94 μmol x L(-1)), estradiol (IC50: 5.26 ± 9.92 μmol x L(-1)), quinestrol (IC50: 6.36?5.37 gmol-L1), estrone (IC50: 6.87 ± 0.03 μmol-L1) and finasteride (IC50: 9.94 ± 0.45 μmol x L(-1)); two drugs, hexestrol (IC50: 14.20 ± 0.55 μmol x L(-1)) and chlormadinone acetate (IC50: 24.60 ± 0.36 μmol x L(-1)), had weak activities against ZEBOV. Further, toremifene citrate, tamoxifen citrate, clomiphene citrate, raloxifene hydrochloride and quinestrol could block both pseudovirus type Sudan ebola virus (SEBOV-GP/HIV) and Marburg virus (MARV-GP/HIV) entries.
Antiviral Agents ; pharmacology ; Drug Evaluation, Preclinical ; Ebolavirus ; drug effects ; physiology ; Hemorrhagic Fever, Ebola ; Humans ; Marburgvirus ; drug effects ; physiology ; Selective Estrogen Receptor Modulators ; pharmacology ; Virus Internalization ; drug effects

BACKGROUND:Many foreign studies confirm that recombinant human growth hormone (rhGH) is a safe and effective agent for treatment of idiopathic short stature (iSS), but there are no long-period and systematical researches reported in China.OBJECTIVE: To observe the promoting effect of rhGH on the growth of children with ISS.DESIGN: Case-control observation.SETTING: Department of Pediatrics, the Affiliated Hospital of Medical College of Qingdao University.PARTICIPANTS: Ninety-eight children with ISS who were treated in the Department of Pediatrics, the Affiliated Hospital of Medical College of Qingdao University during December 2004 to March 2006 were involved in this study.Informed consents were obtained from the guardians of these children with ISS. According to the etiological factors, the children were assigned into 2 groups: ISS group (n =30) and growth hormone deficiency (GHD) group (n =68).METHODS : The children in ISS group and GHD group received subcutaneous administration of home-made rhGH (Jinsai Pharmaceutical Co.,Ltd., Changchun at 0.15 IU/(kg ·d) and 0.1 IU/(kg ·d) respectively before sleeping within 6 months.The body height, body mass and bone age were measured before, 3 and 6 months after treatment. The local region of injection was observed and the growth rate was calculated. Bone age was calculated by graphic atlas method and body height was predicated by BP method.MAIN OUTCOME MEASURES: Body height, body mass, bone age and growth rate of children in two groups before, 3 and 6 months after treatment.RESULTS: All the 98 children wereinvolved in the result analysis, without deletion. ①Intragroup comparison: The body height, growth rate of children in two groups 3 and 6 months after treatment were significantly superior to those before treatment [ISS group: body height:(126.5±9.4), (129.1±8.6), (121.1 ±11.0) cm (P ＜ 0.01), growth rate: (7.3±2.9), (7.5±2.7),(3.5±2.1) cm/year (P＜ 0.01); GHD group: body height: (111.0±13.0),(114.0±13.0),(108.0±12.0) cm(P＜ 0.01),growth rate: (13.2±3.5), (13.5±3.6), (4.0±2.9) cm/year(P ＜ 0.01)]. Six months after treatment, body height was increased in 27 of 30 children in ISS groups, and in all the 68 children in GHD group. ② Intergroup comparison: The growth rate of children in GHD group was concurrently higher than that in ISS group 3 and 6 months after treatment. ③Adverse reaction and side effect: During the treatment, hypothyroidism was observed in 2 children within 1 to 3 months of treatment,but there was no influence on growth rate after oral administration of thyroxin tablets. Local red swelling of skin was observed in another patient, which stopped automatically after one week duration, but the injection continued.CONCLUSION: Home-made rhGH is a safe and effective reagent for treatment of ISS. It can obviously enhance the body height and growth rate of children. Whereas the inhomogeneity of treatment effect does exist, what's more, therapeutic effect in ISS children is inferior to that in GHD children.

This study aimed to investigate the drug susceptibility of wild-type and mutant avian influenza A (H7N9) virus neuraminidase (NA) to oseltamivir and zanamivir. Codon optimized DNA of H7N9 (A/ Hangzhou/1/2013) NA was synthesized and constructed into the pcDNA3.1/His vector (NA(H7N9-WT)). Mutant NA(H7N9-H274Y) and NA(H7N9-R292K) plasmids were constructed by directed mutagenesis PCR using NA(H7N9-WT) plasmid as the template followed by sequencing. NA plasmids were transfected into 293T cells and cell lysates containing NAs were collected 48 h post-transfection. Wild-type and mutant NAs were analyzed by Western blotting and their activities were tested by the 4-MUNANA-based assay. All three NAs were expressed and enzymatic activities were confirmed. The effects of oseltamivir and zanamivir on all three NAs were then tested. It showed that the half maximal inhibitory concentrations (IC50s) of oseltamivir carboxylate on NA(H7N9-WT), NA(H7N9-H274Y) and NA(H7N9-R292K) were 1.6 nM, 15.1 nM, and > 1 000 nM with fold changes of 9 and > 625, respectively. The IC50 values of zanamivir on NA(H7N9-WT), NA(H7N9-H274Y), and NA(H7N9-R292K) were 1.1 nM, 1.4 nM, and 38.0 nM with fold changes of 1.3 and 34, respectively. These results indicated that oseltamivir and zanamivir could significantly inhibit NA(H7N9-WT). NA(H7N9-R292K) showed high-level resistance to both drugs (34-fold and 625-fold) and NA(H7N9-H274Y) was sensitive to both (1.3-fold and 9-fold). These results indicated that both oseltamivir and zanamivir could be used for patients infected with the H7N9 virus. However, when patients carried the H7N9 virus with a NA R292K mutation, other medications would be preferred over oseltamivir or zanamivir.
Antiviral Agents ; pharmacology ; Humans ; Influenza A Virus, H7N9 Subtype ; drug effects ; enzymology ; genetics ; Influenza, Human ; virology ; Microbial Sensitivity Tests ; Mutation ; Neuraminidase ; antagonists & inhibitors ; genetics ; metabolism ; Oseltamivir ; pharmacology ; Viral Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Zanamivir ; pharmacology

Biomedical Research ; Dental Research ; Humans ; Taste ; Taste Buds ; cytology

This study was designed to discover filovirus entry inhibitors in a drug library of commercial medicines. One thousand and six hundred drugs were screened using the ZEBOV-GP/HIV model, a pseudovirus formed by an HIV-core packed with the Zaire Ebola virus glycoprotein. We identified 12 gonadal hormone drugs with inhibitory activities in ZEBOV-GP/HIV entry at final concentration of 10 μmol x L(-1). Among them, three drugs exhibited strong activities with IC50 < 1 μmol x L(-1), such as toremifene citrate (IC50: 0.19 ± 0.02 μmol x L(-1)), tamoxifen citrate (IC50: 0.32 ± 0.01 μmol x L(-1)) and clomiphene citrate (IC50: 0.53 ± 0.02 μmol x L(-1)); seven drugs had moderate activities with IC50 between 1 and 10 μmol x L(-1), such as estradiol benzoate (IC50: 1.83 ± 5.69 μmol x L(-1)), raloxifene hydrochloride (IC50: 3.48 ± 0.07 μmol x L(-1)), equilin (IC50: 4.00 ± 9.94 μmol x L(-1)), estradiol (IC50: 5.26 ± 9.92 μmol x L(-1)), quinestrol (IC50: 6.36?5.37 gmol-L1), estrone (IC50: 6.87 ± 0.03 μmol-L1) and finasteride (IC50: 9.94 ± 0.45 μmol x L(-1)); two drugs, hexestrol (IC50: 14.20 ± 0.55 μmol x L(-1)) and chlormadinone acetate (IC50: 24.60 ± 0.36 μmol x L(-1)), had weak activities against ZEBOV. Further, toremifene citrate, tamoxifen citrate, clomiphene citrate, raloxifene hydrochloride and quinestrol could block both pseudovirus type Sudan ebola virus (SEBOV-GP/HIV) and Marburg virus (MARV-GP/HIV) entries.