This investigation describes a new precise, sensitive and accurate stereoselective RP-HPLC method for determination of the enantiomers of a novel alpha- and beta-receptor blocking agent, 1-[4-(2-methoxyethyl) phenoxy]-3-[[2-(2- methoxyphenoxy) ethyl]amino]-2-propanol (TJ0711), in rat plasma. GITC was used for precolumn derivatization of TJ0711 enantiomers. Enantiomeric resolution was achieved on a Eurospher-100 C18 column (250 mmx4.6 mm ID, 5-mum particle size), with UV detection at 255 nm, and the mobile phase consisted of acetonitrile and water (58:42, v/v) containing 0.02% glacial acetic acid (v/v). Using the chromatographic conditions described, TJ0711 enantiomers were well resolved with mean retention time of 10.2 and 11.5 min, respectively. Linear response (r>0.999) was observed over the range of 0.125-12.5 mug/mL of TJ0711 hydrochloride enantiomers. The mean relative standard deviation (RSD%) of the results of within-day precision was [Symbol: see text] 10%. The proposed method was found to be suitable and accurate for the quantitative determination of TJ0711 enantiomers in rat plasma, and it can be used in pharmacokinetic studies.

Objective To compare the clinical efficacy of catheter directed thrombolysis(CDT ) ,thrombectomy(ST ) and system‐atic anticoagulant(SA) in treating acute iliofemoral deep vein thrombosis(AIFDVT ) of lower limb using Meta analysis method . Methods The systematic review was initialted by electronic literature searches (PUBMED ,MEDLINE ,ELSEVIER ,etc .) for stud‐ies comparing catheter directed thrombolysis ,thrombectomy and systematic anticoagulant clinical effects published from January 1984 to January 2014 based on the keyword such as iliofemoral deep vein thrombosis;thrombolysis;anticoagulant therapy ;throm‐bectomy ;RCTs;Meta analysis.A Meta analysis was conducted to estimate early vein patency ,post thrombotic syndrome(PTS) , venous reflux(VR) rate ,venous obstruction(VO) rate ,etc .Results Ten RCTs were included in this analysis ,including 626 pa‐tients .The early vein patency rate was higher in the CDT group and the difference was statistically significant(OR=4 .61 ,95% CI 1 .93-10 .98 ,P<0 .05);there was no statistically difference between ST and SA group(OR= 2 .54 ,95% CI 0 .49 -13 .24 ,P>0 .05) .The post thrombotic syndrome rate was less both in the CDT group(OR=0 .18 ,95% CI 0 .07 -0 .43 ,P< 0 .05) and ST group(OR=0 .50 ,95% CI 0 .28 -0 .87 ,P< 0 .05);the difference was statistically significant .The difference of the venous reflux rate was not statistically significant in both two groups .The venous obstruction rate was less in the CDT group(OR=0 .19 ,95% CI 0 .11-0 .34 ,P<0 .05) and the difference was statistically significant ;while the difference was not statistically significant between ST and SA group (OR=1 .53 ,95% CI 0 .72-3 .26 ,P>0 .05) .Conclusion For acute iliofemoral deep vein thrombosis(AIFDVT) , short term (< 7 d) outcomes of catheter directed thrombolysis was better than anticoagulant therapy ,but thrombolysis brought more bleeding .In long term(>6 m) outcomes ,the post thrombotic syndrome rate was less both in the thrombolysis group and the thrombectomy ,and catheter directed thrombolysis could diminish the vein obstruction rate .

To further explore the result of bilingual teaching in pediatrics,we randomly chose 200 undergraduates of 4 class and released students'questionnaires about bilingual teaching with teaching content before and after class to assess students'understanding of bilingual teaching and analysed appraisal result.We found no significant difference of student score between students accepting bilingual teaching and not accepting the bilingual teaching,but there was difference for English tests and expression level.So we think that students can fully accept the bilingual teaching of pediatrics under the premise with selecting appropriate teaching methods and means.

This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate. The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium. In vitro release was detected by a dialysis method in reverse. The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes. The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique. The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting. Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500. The MDZ was completely released in 10 h. A significant decrease in the formation of 1'-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed. A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250. This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.

Cinobufacino injection is a significant anti-tumor medicine for the treatment of various tumors in clinic, which was made from water extraction of the skin of Bufo bufo gargarizans. In present paper, HPLC-DAD-FT-ICR-MS method was used to identify the major bufadienolides in cinobufacino for the first time. Solid-phase extraction with dichloromethane and silica was used to enrich the total bufadienolides in cinobufacino. Based on the UV and high resolution MS/MS data, 33 bufadienolides were analyzed and characterized. Among them, eight compounds were identified by comparing with standard references unambiguously. This study elucidated the major bufadienolides in cinobufacino, which provided material foundation of cinobufacino and will be benefit for the further pharmacological research.
Amphibian Venoms ; chemistry ; Animals ; Bufanolides ; analysis ; chemistry ; Bufo bufo ; Chromatography, High Pressure Liquid ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

Cinobufacino injection is purified from water extraction of the skin of Bufo bufo gargarizans, which has been widely used for various cancers in clinic with significant anti-tumor effects. Bufadienolides were regarded as the main active constituents of cinobufacino injection in previous reports. In present study, 6 bufadienolides were isolated and purified from Cinobufacino injection. Their structures were identified as 3-epi-ψ-bufarenogin (1), ψ-bufarenogin (2), 3-epi-arenobufagin (3), arenobufagin (4), 3-epi-gamabufotalin (5), and 3-oxo-arenobufagin (6), separately. Among them, 1 and 3 were new compounds, 5 and 6 were new natural products. Compounds 1, 2 and compounds 3, 4 were two pairs configuration isomers at C-3, separately.
Animals ; Bufanolides ; chemistry ; isolation & purification ; Bufo bufo ; Injections ; Skin ; chemistry

Objective To investigate the expression of peroxisome proliferators-activated receptor ? (PPAR?) in trophoblast and relation between PPAR? ligands and trophoblast invasion.Methods We examined the expression of PPAR? by immunohistochemistry,immunocytochemistry and real time quantitative PCR.We next examined,using the cytotrophoblast culture model,the biological role of PPAR? ligands in vitro.Results PPAR? was mainly localized in the nuclei of villous cytotrophoblast and extravillous cytotrophoblast of cell islands and cell columns.In villous tissue and cultured trophoblast from early first trimester,the level of expression of PPAR? mRNA and protein was 36.0?5.1,13.4?3.1 and 1.35?0.08,1.13?0.11;from late first trimester it was 23.3?5.5,6.1?1.3 and 1.17?0.03,0.86 ?0.05,and the expression of PPAR? was obviously decreased (P

To investigate the inhibitory effect of Pluronic on P-glycoprotein (P-gp) drug efflux pump, Caco-2 cells and animal models were established to study the influence of Pluronic on celiprolol transport across Caco-2 cell monolayer and intestinal mucous membrane with verapamil set as a positive control. Drug concentration was measured by HPLC and the apparent permeability coefficient (P(app)), absorption rate constant (k(a)) and the effective permeability coefficient (P(eff)) were calculated. P(app) of basolateral to apical side and apical to basolateral side was (2.10 +/- 0.13) x 10(-6) and (0.333 +/- 0.018) x 10(-6) cm x s(-1), respectively. Transports of celiprolol across Caco-2 cell monolayer were influenced by both verapamil and Pluronic. The absorption constants (k(a)) of celiprolol at duodenum, jejunum, ileum, and colon were (0.09 +/- 0.03), (0.14 +/- 0.04), (0.11 +/- 0.03) and (0.05 +/- 0.02) h(-1), k(a) of celiprolol in verapamil group were (0.14 +/- 0.03), (0.24 +/- 0.02), (0.25 +/- 0.03) and (0.23 +/- 0.02) h(-1), and k(a) of celiprolol in Pluronic group were (0.13 +/- 0.02), (0.22 +/- 0.02), (0.22 +/- 0.03) and (0.20 +/- 0.03) h(-1), respectively. Pluronic showed significant effect on inhibiting P-gp of Caco-2 cell and intestinal mucosa in rats.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Biological Transport ; drug effects ; Caco-2 Cells ; Celiprolol ; pharmacokinetics ; Excipients ; Humans ; Intestinal Absorption ; drug effects ; Intestinal Mucosa ; metabolism ; Jejunum ; metabolism ; Male ; Permeability ; Poloxamer ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley

Objective To investigate the effects of selective cyclooxygenase 2 inhibitor on the hyperplasia of parathyroid glands from uremic rats. Methods Sixty-five 5/6-nephrectomized (Nx) and fifteen sham operated rats were assigned to 4 groups: (1)Sham group (n=14):shamoperated +normal phosphate diet (P 0.8％,Ca 1.2％)； (2) Nx-HP group (n=17):Nx+high phosphate(HP) diet (P 1.2％,Ca 1.2％)； (3)Prophylactic COX2 inhibition group (Prey group,n=18):Nx+HP+celecoxib 100 mg· kg-1·d-1 for 3 months； (4)Therapeutic group (Ther group,n=18):Nx+HP+celecoxib 100 mg·kg-1·d-1 starting at the second month of the 5/6 nephrectomy.At the end of 3 month,blood,urine and parathyroid samples were collected.The expressions of COX2 and PCNA were determined by immunohistochemistry,Western blotting and real-time PCR. Results All of the Nx rats fed with high phosphate diet for 3 months manifested progressively increasing serum creatinine,serum iPTH as well as augmentation of parathyroid gland volume,suggesting that secondary parathyroid hyperplasia animal model was established successfully.Celecoxib significantly decreased serum iPTH levels [Sham (34.77±0.83),Nx-HP(100.73±4.35),Prey (87.36±2.18),Ther (87.47±1.76) ng/L,P＜0.05],the size of the parathyroid glands in Nx rats [Sham (0.461±0.089),Nx-HP (2.436±0.372),Prey (0.987±0.254),Ther (1.27±0.305) mm2/kg,P＜0.05] and PCNA expression in PG determined by Western blotting (decreased to 52.91％ in Prev group and 34.68％ in Ther group respectively,P＜0.05).No significant difference was observed between the two COX2 inhibition groups.The levels of COX2 expression in parathyroid gland were greatly increased in three Nx groups compared with that in sham group (2.47-fold in Nx-HP,2.34-fold in Prey group,3.04-fold in Ther group,P＜0.05).COX2 inhibitor had no effects on COX2 expression in PGs.Real-time PCR analysis demonstrated the same trends of mRNA expression of COX2 and PCNA in PGs of rats. Conclusion Selective inhibition of COX2 may help to suppress the hyperplasia of parathyroid glands in uremic rats.

To evaluate the effects of p-octyl polyethylene glycol phenyl ether (Triton X-100), polyoxyl 35 caster oil (EL35) and polyoxyl 40 hydrogenated caster oil (RH40) on the activity of Cytochrome P450 3A (CYP3 As) in vivo. Rats were administered with saline, ketoconazole (75 mg x kg(-1) x d(-1)), Triton X-100 (30 mg x kg(-1) x d(-1)), EL35 (150 mg x kg(-1) x d(-1)) and RH40 (150 mg x kg(-1) x d(-1)) intragastrically for 5 consecutive days, and then given midazolam 10 mg x kg(-1) 20 min after the last treatment of ketoconazole or three surfactants with the same dose through duodenal administration. Pharmacokinetics parameters for midazolam and its metabolite 1'-hydroxymidazolam were estimated from the plasma concentration-time data by a noncompartmental approach. The results showed that multiple dose administration of Triton X-100, EL35 and RH40 decreased the ratios of 1'-hydroxymidazolam and midazolam AUC0-infinity from 1.14 to 0.90, 1.03 and 0.64, respectively. In contrast, multiple dose administration of ketoconazole caused the ratios of 1'-hydroxymidazolam and midazolam a significant decrease to 0.50. This study indicated that Triton X-100 and EL35 would have no inhibition on CYP3A, while RH40 had significant inhibition on CYP3A. Therefore, RH40 might be used to prepare drug formulations in pharmaceutical industry and would increase the bioavailability of some drugs transformed by CYP3As and further lead to significant clinical pharmacologic effects.
Animals ; Area Under Curve ; Biological Availability ; Biotransformation ; Cytochrome P-450 CYP3A ; metabolism ; Ketoconazole ; pharmacology ; Male ; Midazolam ; analogs & derivatives ; pharmacokinetics ; Octoxynol ; pharmacology ; Polyethylene Glycols ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Surface-Active Agents ; pharmacology