AIM:To establish HPLC method for the determination of amodiaquine in human plasma.METHODS: Amodiaquine and internal standard(hydroxychloroquine) were analyzed on C18 column(150 mm ×4.6 mm, 5 μm) with methanol: water:triethylamine: orthophosphoric acid (21:77.5:1:0.5 )as mobile phase at the flow rate of 1.0 mL · min-1The UV detector was set at 294 nm. RESULTS: The retention times of amodiaquine and internal standard were 5.82, 8.56 min, respectively. The calibration curve was linear in the range from 10 to 1 000 μg ·L- 1 ( r = 0.999 8, n = 9 ). The limit of quantitation was5 μg· L-1. The extraction recovery was between 75.5 % and 82.7 %, and the methodological recovery was between 97.0 % and 104.8 %. The intra-day and inter-day RSD were less than 6.0 % and 7.5 %, respectively. CONCLUSION: This HPLC method is simple, sensitive and suitable for pharmacokinetic study of amodiaquine.

OBJECTIVE: To establish a HPLC method for content determination of gatifloxacin in human plasma.METHODS: The Analytical column was C18,the mobile phase consisted of acetonitrile-30mmol/L ammonium acetate-triethylamine-orthophosphoric acid (20∶80∶1.0∶0.7) with a flow rate of 1.0ml/min,the detection was performed at UV 294nm.RESULTS: The calibration curve was linear in the concentrations ranging from 0.1 to10.0?g /ml (r=0.9 992).The detection limit was 0.05?g/ml.The intraday RSD was less than 8% and interday RSD was less than 10%.The average recovery was (101.67?3.06)%.CONCLUSION: The method is simple, sensitive, accurate and suitable for determination of gatifloxacin in human plasma and pharmacokinetic study.

Aim To investigate the reversal effect of cinobufacine(Cino)on adrimycin(ADM)resistant human breast cancer cell line MCF-7/ADM.Methods The cytotoxic effect of Cino or ADM and the sensitivity of ADM to cells was determined by MTT assay.The intracellular concentration of ADM was detected by HPLC. The expression of P-glycoprotein(P-gp)was examined by flow cytometric(FCM) .Results The maximum non-toxic dose Cino(15 mg?L-1) increased the sensitivity of ADM in MCF-7/ADM,decreased the IC50 of ADM in MCF-7/ADM from 38.14 mg?L-1 to 12.93 mg?L-1, and significantly increased the intracellular concentration of ADM in MCF-7/ADM and reduced the expression of P-glycoprotein.Conclution The results showed that Cino can partially reverse multidrug resistance(MDR)of MCF-7/ADM cells and the mechanism might be associated with the increase of intracellular accumulation of ADM and the reduced expression of P-glycoprotein(P-gp)in MCF-7/ADM cells.

OBJECTIVETo observe the effect of heart protection on diabetic cardiomyopathy in rats by tripterysium glucosides.

METHODThe rat diabetic cardiomyopathy rats model are made by streptozotocin, then divided into tripterysium glucosides group (n=8) and model group (n=8). In addition, the control group is established (n=8). Glucosides group was orally administrated tripterysium glucosides (18 mg x kg(-1)), the control groups was orally administrated same volume NS for 3 months. Blood sugar, heart function and cardiac index were detected after 3 months. Immunohistochemical techniques were used to detect NF-kappaB and ICAM-1 expression. Ultrastructure of cardiac muscle cell were observed by electronmicroscope.

RESULTCompared with model group, cardiac index was decreased after tripterysium glucosides administration, and LVSP, LVEDP, + dp/dtmax, -dp/dtmax, were improved, and the expression of nuclear Factor-kappaB (NF-kappaB) and intercellular adhension molecule-1 (ICAM-1) was inhibited. Ultrastructure of cardiac muscle cell such as mitochondrion and cardiac muscle fibers was atttenuated.

CONCLUSIONTripterysium glucosides could protect rat diabetic cardiomyopathy rats heart. These function may be related to inflammatory reaction inhibition and immunosuppression of tripterysium glucosides.

Animals ; Blood Glucose ; metabolism ; Cardiomyopathies ; etiology ; metabolism ; pathology ; physiopathology ; Diabetes Mellitus, Experimental ; complications ; Gene Expression Regulation ; drug effects ; Glucosides ; administration & dosage ; pharmacology ; therapeutic use ; Heart ; drug effects ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Myocardium ; ultrastructure ; NF-kappa B ; metabolism ; Rats

Objective: To explore the changes of pulmonary function in type 2 diabetes and its related factors.Methods: The pulmonary functions of 72 patients with type 2 diabetes and 22 healthy objects were measured,and the related factors,such as duration of DM,HbA1c,BMI,were analysed with linear regression analysis.Ninteen of them underwent a 12-week-long intensive insulin therapy and pulmonary function tests before and after the treatment.Results: Vital capacity(VC),forced vital capacity(FVC),forced expiratory volume in the first second(FEV1),total lung capacity(TLC) and carbon monoxide diffusion in the lung(DLco) were significantly decreased in the diabetes patients.Correlation analysis revealed that DLco was negatively correlated with the duration of DM.which was shown by linear regression analysis to be the only significant predictor.After a 12-week-long intensive insulin therapy,DLco and DLco/VA decreased significantly.Conclusion:Patients with type 2 diabetes have abnormal pulmonary ventilatory function and impaired pulmonary diffusive function,and the latter is related to the time of hyperglycemia,and can not ameliorated by short-term glycemic control.

Objective To investigate the anti-tumor effect of ultrasound-targeted microbubble destruction (UTMD) mediated herpes simplex virus thymedine kinase (HSV-TK) on mice ovarian cancer.Methods Forty female BALB/c-nu mice were randomly divided into four groups after the models of subcutaneous transplantation tumors were established:(A)HSV-TK + Microbubbles + Ultrasound (HSV-TK+ MBs + US);(B) HSV-TK+ Ultrasound (HSV-TK + US);(C) HSV-TK;(D) PBS.TheTK protein and mRNA expression were separately detected by western-blot and real time RT-PCR.TUNEL staining was used to detect the tumor cell apoptosis.The inhibition rates and survival time of the animals were compared among all groups.Results The HSV-TK gene transfection efficacy and tumor inhibitory effect of HSV-TK on mice transplantable tumor in group A (HSV-TK + MBs + US) were significantly improved compared with group B (HSV-TK + US),group C (HSV-TK) and group D (PBS) (P ＜0.05).However,group A has no significant difference (P ＞0.05) with other groups in improving the survival time of tumor-bearing mice.Conclusions Ultrasound-targeted microbubble destruction can effectively transfect HSV-TK gene into target tissues and play a significant inhibition effect on ovarian cancer in mice.However,this new method is not able to improve the survival time of mice for a short-term observation.

0.05)in healthy volunteers.

OBJECTIVETo study the effects of Ginkgo biloba extract (GBE) on the pharmacokinetics and pharmacodynamics of warfarin and observe the anticoagulant activity of GBE.

METHODA randomized, double-blinded, placebo-controlled, two-way cross-over trial was conducted. Twelve healthy volunteers (sex ratio was 1: 1) were randomized into two groups and received GBE (three pill, tid) or placebo (three pill, tid) for 5 weeks respectively. the subjects received a single dose of warfarin (5 mg) on the day 29. Blood samples for pharmacokinetics and pharmacodynamics assessment were collectd.

RESULTCompared with placebo, BE had no significant pharmacodynamics effects on warfarin and had no effects on prothrombin time (PT) and activated partial thromboplastin time (APTT). GBE extract increased C(max), AUC(0-144 min), AUC(0-infinity), t1/2, of warfarin significantly and decreased CL(F) of warfarin significantly (P < 0.05), and there were no singnificant difference of V(d) (F).

CONCLUSIONGBE has limited effects on the pharmacokinetics but no effects on the pharmacodynamics of single dose warfain in health subjects. GBE has no effects on clotting process alone.

Adult ; Anticoagulants ; pharmacology ; Double-Blind Method ; Female ; Ginkgo biloba ; Herb-Drug Interactions ; Humans ; Male ; Plant Extracts ; pharmacology ; Warfarin ; blood ; pharmacology ; Young Adult

Objective:To establish the fingerprint analysis method for the root of Rosa laevigata Michx from different regions by UPLC. Methods:The column was ACQUITY UPLC? Phenyl(2.1 mm × 100 mm,1.7 μm). The mobile phase consisted of methanol-water with gradient elution. The flow rate was 0. 2 ml·min-1 , the detection wavelength was 210 nm, the column temperature was 30℃, and the injection volume was 3 μl. Results:The fingerprint consisted of 15 common peaks. The range of similarity for twelve bat-ches of the root of R. laevigata Michx was 0. 489-0. 942. And the reference fingerprint of the root of R. laevigata Michx was estab-lished by UPLC. Conclusion:The fingerprint method is simple and reproducible, which can provide basis for the quality control and the medicinal resources exploration.

PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEPO6 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.