The aim of the study is to prepare flurbiprofen axetil nanoemulsion-in situ gel system (FBA/NE-ISG) and observe its ocular pharmacokinetics, rheological behavior, TEM images, irritation and cornea retention. Production of nanoemulsion was based on high-speed shear and homogenization process, and then mixed with gellan gum to prepare FBA/NE-ISG. Rheological study showed that FBA/NE-ISG possesses strong gelation capacity and its viscosity and elastic modulus increases by 2 Pa*s and 5 Pa respectively when mixed with artificial tear at the ratio of 40 : 7. TEM images suggested no significant changes in particle morphology of the pre and post gelation. Good ocular compatibility of FBA/NE-ISG was testified by the irritation test based on histological examination. In vivo fluorescence imaging system was applied to investigate the characteristics of cornea retention, and the results indicated that the nanoemulsion-in situ gel (NE-ISG) prolonged the cornea retention time significantly since K(NE-ISG) (0.008 5 min(-1) was much lower compared with flurbiprofen sodium eye drops (FB-Na, 0.03% w/v) of which the K(Eye drops) was 0.105 2 min(-1), indicated that the cornea retention time of NE-ISG was prolonged significantly. Pharmacokinetics of FBA/NE-ISG in rabbit aqueous humor was studied by cornea puncture, the MRT (12.3 h) and AUC(0-12h) (126.8 microg x min x mL(-1)) of FBA/NE-ISG was 2.7 and 2.9 times higher than that of the flurbiprofen sodium eye drops respectively, which meant that the ocular bioavailability was improved greatly by the novel preparation. Therefore, FBA/NE-ISG can enhance the ocular bioavailability by prolonging drug corneal retention significantly. What's more, encapsulated by emulsion droplets prodrug flurbiprofen (FBA) instead of flurbiprofen (FB) can reduce the ocular irritation.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; adverse effects ; pharmacokinetics ; Aqueous Humor ; metabolism ; Biological Availability ; Cornea ; cytology ; drug effects ; Emulsions ; Female ; Flurbiprofen ; administration & dosage ; adverse effects ; analogs & derivatives ; pharmacokinetics ; Gels ; Male ; Nanoparticles ; Ophthalmic Solutions ; Rabbits ; Rheology ; Viscosity

The aim was to prepare a novel ocular cationic microemulsion-in situ gel (CM-ISG) system with vitamin A palmitate (VAP) as model drug, and investigate the corneal retention behavior and corneal irritation of the system. VAP/CM was prepared by a process based on supply of energy, and the before-and-after gelation rheology of VAP/CM-ISG was investigated. In vitro VAP release and gel dissolution of both VAP/CM-ISG and Oculotect Gel was determined. And in vitro corneal retention behavior of both formulations was evaluated by captive bubble technique. Ocular irritation test was carried out based on the Draize method. Images of TEM showed that homogenous VAP/CM was made, and no significant differences of particle size were found between the VAP/CM and VAP/CM in Poloxamer 407 gel. Rheology study illustrated that VAP/CM reduced the phase transition temperature of Poloxamer 407 gel by 1.5 degrees C, and the elastic modulus increased about 15.7 times. The in vitro release and gel dissolution profile of both formulations exhibited the characteristics of zero order kinetics. Comparing with Oculotect Gel, desorption kinetics study of VAP/CM-ISG exhibited longer corneal retention time and smaller contact angle. Irritation test showed a good ocular compatibility of VAP/CM-ISG. Therefore, VAP/CM-ISG combined both advantages of the cationic microemulsion and in situ gel system, provided better wettability and longer ocular retention time. It might be a promising ocular drug delivery system.
Animals ; Cornea ; drug effects ; metabolism ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Emulsions ; Ophthalmic Solutions ; Poloxamer ; chemistry ; Rabbits ; Random Allocation ; Viscosity ; Vitamin A ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; toxicity

Abdominal Pain ; etiology ; Adult ; Chemical and Drug Induced Liver Injury ; etiology ; Drug Eruptions ; complications ; therapy ; Humans ; Male ; Nausea ; etiology ; Treatment Outcome

Abdominal Neoplasms ; secondary ; surgery ; Abdominal Wall ; Antiporters ; metabolism ; Choriocarcinoma ; pathology ; Diagnosis, Differential ; Epithelioid Cells ; pathology ; Female ; Gestational Trophoblastic Disease ; metabolism ; pathology ; secondary ; surgery ; Humans ; Pregnancy ; Uterine Neoplasms ; metabolism ; pathology ; surgery ; Young Adult

Objective To explore the significance and the change of miRNAs expression profile in different period of HBV infection.Methods Establish the detection method of microRNA(miRNA) by RNA DNA probe liquid chip (flexible multi-analyte profiling,xMap) and estimate the specificity,repeatability and accuracy of this method.From October 2010 to October 2011,collect HBV infected patients' periphcral blood of the First affiliated hospital of SooChow University,including acute hepatitis B,chronic hepatitis B,hepatits B liver cirrhosis,liver cancer patients and health control,each group contains 40 cases.The levels of miR-191,-223,-222,-145,-21,-31,-126,-20a,-372 of peripheral blood mononuclear cell were detected by xMap liquid chiptechnology.The level of miR-103 was taken as reference.The ratio of (the mean fluorescence intensity of target miRNAs-corresponding backgroud mean fluorescence intensity)/( the mean fluorescence intensity of miR-103-corresponding backgroud mean fluorescence intensity) as a valid data and analysis the characteristics of miRNAs expression.The SPSS 17.0 was used as statistical software.The single factor analysis of variance was used as the method to analysis group comparison,and make multiple comparison by the LSD-t method if the result with a significant difference.Results The specificity of Xmap liquid chip method to detect miRNAs was 100％ ;The repeated experiment proved that the CV value was less than 5％ in the high value reference miRNA test,less than 10％ in the low value reference miRNAs test;the accruracy experiment proved that the recovery rate was ( 100 ± 5)％ in the nine miRNAs.There were no statistically differences with miR-222 ( F =1.32,P ＞ 0.05),-191 ( F =1.98,P ＞ 0.05),-145 ( F =0.78,P＞0.05),-21(F=0.64,P ＞0.05),-31 (F =0.83,P ＞0.05),-372(F =1.75,P ＞0.05)in different groups; There was statistically significant differences in miR-223 ( F =14.56,P ＜ 0.05) among different groups,with the highest expression level in actue hepatitis B group (15.37 ± 4.01),and the lowest expression level in liver cancer group (6.91 ±3.18) ; There was statistically significant differences in miR126 (F =17.43,P ＜ 0.05)among different groups,with the highest expression level in health control group (6.33 ±2.75) and the lowest expression level in liver cancer group (2.38 ± 1.07).There were statistically significant differences in miR-20a ( F =19.484,P ＜ 0.05) among different groups,with the highest expression level in health control group (0.33 ±0.18) and the lowest expression level in liver cancer group (0.81 ±0.24).Conclusion The detection method of miRNA by Xmap liquid chip has strong specificity,high accuracy and good repeatability,suitable for large throughput clinical testing.The study for miRNA in HBV infected diseases provides a new clue to the research of chronic progress mechanism.

Objective To investigate the effect of recombinant adenovirus mediatied human endostatin (rAD-GFP-ES)on rats with collagen typeⅡinduced arthritis(CIA),and explore the mechanism of inflamma- tion and cytokines inhibition on rats CIA.Methods The rAD-GFP-ES was amplified and purified.The model of rat CIA was induced by intradermal injection of typeⅡcollagen combined with complete Freund's adjuvant(CFA). On the second day after the injection,the therapeutic administration of rAD-GFP-ES(1?10~(11)pfu?kg~(-1)?week~(-1)?4 weeks)were performed to the rats.The mean arthritis index(AI)was scored every week since then.The relative concentrations of ES,IL-I?,TNF-?in sera collected at the fourth week were evaluated by western blotting. Results①The titer of the purified rAD-GFP-ES and rAD-GFP was 6.6?10~(12)pfu/ml and 4.8?10~(12)pfu/ml,re- spectively(A_(260nm)/A_(280nm)＞1.3).②The concentration of ES in sera of the group treated with rAD-GFP-ES was 2.4-lold higher compared to the normal group.③The mean arthritis index of the group treated with rAD-GFP- ES was much lower than that of the model group.The administration of rAD-GFP-ES could significantly de- creas the production of IL-1?and TNF-?in sera.Conclusions①The rAD-GFP-ES is efficiently expressed in vivo.②The rAD-GFP-ES has an inhibitory effect on the arthritis index of rat CIA.③IL-1?and TNF-?are involved in the pathogenesis of RA.The rAD-GFP-ES has an inhibitory effect on the expression of IL-1?and TNF-?in rat CIA.

Congresses as Topic ; Digestive System Diseases ; diagnosis ; therapy ; Humans ; Integrative Medicine

Adenocarcinoma ; pathology ; Aged ; Ciliary Body ; pathology ; Epithelium ; pathology ; Female ; Humans ; Uveal Neoplasms ; pathology

Actins ; metabolism ; Adult ; Antigens, Neoplasm ; metabolism ; Diagnosis, Differential ; Epithelioid Cells ; chemistry ; pathology ; Female ; Humans ; Hysterectomy ; Immunohistochemistry ; Melanoma-Specific Antigens ; Mesenchymoma ; metabolism ; pathology ; surgery ; Neoplasm Proteins ; metabolism ; Uterine Neoplasms ; metabolism ; pathology ; surgery

Objective To understand the status of drinking-water supply and the progress of waterimproving projects in drinking-water-borne endemic fluorosis areas in Henan,and to provide scientific data for related government departments to carry out prevention and surveillance plan for those areas.Methods Questionnaire survey was carried out in all the villages in drinking-water-borne endemic fluorosis areas in Henan in 2010.Each village was given one set of questionnaire.Results By the end of 2010,the total number of fluorosis villages in Henan was 25 434,among them 11 484 villages had been conducted water-improving projects,accounting for 45.15％.Currently,9267 water-improving projects worked properly,accounting for 36.4％(9267/25 434)of all villages surveyed,and 80.7％ (9267/11 484)villages had water-improving projects.The projects in 2217 villages do not work properly,accounting for 19.3％(2217/11 484) of all projects.There were 5832 water-imp.roving projects conducted amnog 2005-2010,accounting for 50.8％ (5832/11 484) of all water-improving projects.Among villages with no such projects,97.5％(15 769/16 167) of them used shallow groundwater,and in villages with water-improving projects,89.6％ (8303/9267) of them used deep groundwater as drinking-water supply.Conclusions After 2005,the water improving progress was significantly speed up in drinking-water-borne endemic fluorosis areas in Henan,but progress of the water improving projects is relatively slow due to changing and expanding of fluorosis areas.The government should increase investment and improve the proportion of waterimproving defluoridation.