Objective:To study the pharmacokinetics and relative bioavailability of isosorbide 5 mononitrate(5 ISMN)sustained release capsules in 12 male healthy volunteers. Methods: A capillary gas chromatography method with electron captured detector was established for the determination of 5 ISMN in plasma, after administrating a daily dose of 40 mg 5 ISMN domestic and imported sustained release capsules in a randomized crossover design.The fluctuation of 5 ISMN valley concentrations observed and the steady state pharmacokinetics was characterized in a multiple dose schedule of 40 mg 5 ISMN sustained release capsules.Results:The steady state of 5 ISMN plasma concentrations reached at the fourth oral administration.The steady state pharmacokinetic parameters after multiple oral dose of 40 mg 5 ISMN domestic and imported sustained release capsules were as follows: t max were (4.8?0.6) and (4.8?0.9) h, c max were (802.46?94.45) and (807.09?109.16) ?g/L, c min were (127.83?23.76) and (121.85?22.00) ?g/L, AUC ss were (8 114.7?1 393.4) and (8 174.8?1 219.7) ?g?h/L, c av were (338.12?58.06) and (340.62?50.82) ?g/L,the degree of fluctuation (DF) were (2.04?0.39) and (2.03?0.33), respectively. Conclusion:The relative bioavailability of multiple oral dose of 40 mg domestic 5 ISMN sustained release capsules is (99.07?5.45)%, there are no significant differences in the main steady state pharmacokinetic parameters between domestic and imported sustained release capsules, and so the 2 capsules are bioequivalent.

Object To estabish a method for the quantitative analysis of osthol in LOTIO FRUCTUS CNIDII COMPOSITA by RP HPLC Methods Megestrol acetate was used as the internal standard Results Chromatographic separation of osthol and megestrol acetate was accomplished within 12 min on Hypersil ODS 2(200 mm? 4 0 mm, 5 ?m) column and acetonitrile 0 01 mol/L sodium dihydrogen phosphate (48∶52) as mobile phase The flow rate was 1 2 mL/min and the detection wavelength was 320 nm A good linearity was obtained in the range of 0 123 8～2 970 ?g/mL (r=0 999 6) for osthol and the average method recovery was (98 4?0 90) % with RSD=0 91% Conclusion The method was simple, rapid, accurate, reliable, and suitable for the quality control of LOTIO FRUCTUS CNIDII COMPOSITA

Objective: To evaluate pharmacokinetic and pharmacodynamic of repaglinide tablets in Chinese subjects.Methods: Twenty healthy male volunteers were enrolled in the study. A single dose (4 mg) of repaglinide tablets was givenorally. Plasma concentrations of repaglinide were determined by HPLC method. Blood glucose and serum insulin leve1s weremeasured by biochemistry and radioimmunoassay methods respectively. Results: Plasma concentration-time curve conformedto one-compartment open model. The pharmacokinetic parameters were as follows: tmax (0. 75?0.43 ) h,cmax (54.44?24.97)ng/ml, t1/2 (0. 80?0. 31) h, MRT (1. 55?0. 41) h, C1/F (61. 43?20. 10) L/h and AUC (73. 34?29.95) h? ng/ml. Thelevel of serum insulin was raised and the level of blood glucose decreased after administration of repaglinide. The highest levelof serum insulin was (l26. 24?95.93) mU/L at 0.75h and blood glucose level reached its lowerest vaIue (2. 34I0.44) mmol/L 1 h after oral administration. Conclusion: Repaglinide is characterised by fast-acting and short effects on in-sulin secretion. It decreases serum glucose level by stimulating insulin secretion from the pancreatic ?-cells. It is a novel oralprandial glucose regulator for the treatment of type 2 diabetes mellitus.

OBJECTIVE:To compare the qualities of six kinds of Nimodipine tablet in terms of dissolubility METHODS:According to Appendix of Chp(2000),the dissolubilities of six kinds of Nimodipine tablet in ethanol,artificial gastric juice and artificial intestinal juice were determined respectively RESULTS:The dissolubility of domestic dispersion tablets was not as good as that of imported products but was obviously superior to that of other domestic products CONCLUSION:Owing to the use of advanced solid dispersion technic,Nidaer tablet is better than other domestic Nimodipine tablets in quality and its price is lower than that of similar imported product

Objective To explore the impact of nucleos(t)ide analogue antiviral therapy on anxiety and depression of patients with chronic hepatitis B (CHB),and analyze the related factors.Methods Before nucleos(t)ide analogue antiviral therapy,1 year and 2 years after antiviral therapy,120 CHB patients were investigated with self-rating anxiety scale (SAS) and self-rating depression scale (SDS).The demography data of patients were collected.Serum levels of alanine transaminase (ALT) and hepatitis B virus (HBV) DNA and other biochemical indicators were measured regularly.Results Before nucleos(t)ide analogue antiviral therapy,1 year and 2 years after antiviral therapy,both the mean scores of SAS and SDS became lower gradually (F=12.661 and 22.395,respectively;both P＜0.01).The percentage of patients with SAS and SDS scores more than 50 were 5.8％,4.2％,1.7％ and 13.3％,7.5％,5.0％,respectively.After 2 years of therapy,the anxiety improvement rate of the patients obtained HBV DNA＜1000 copy/mL was 69.0％,while those with HBV DNA≥1000 copy/mL was 22.2％ (x2 =22.325,P＜0.01).Meanwhile,after 2 years of therapy,the depression improvement rate of the patients obtained HBV DNA＜1000 copy/mL was 77.4％,while those with HBV DNA≥1000 copy/mL was 22.2％ (x2 =32.179,P＜0.01).Multiple factors Logistic regression analysis indicated that the odds ratios (OR) of improvement of anxiety and depression in patients with HBV DNA＜1000 copy/mL were 7.751 (95％ CI:3.026-19.853) and 15.069(95％ CI:5.309-42.770),respectively,compared with those with HBV DNA≥1000 copy/mL; and OR of improvement of depression in patients with ALT≤40 U/L waa 4.103 (95％ CI: 1.376 - 12.238).Conclusions Nucleos(t) ide analogue antiviral therapy could improve the anxiety and depression of CHB patients.The HBV DNA negativity is the independent impact factor of improvement of anxiety and depression in CHB the patients.

Objective：To evaluate bioequivalence and relative bioavailability of domestic and imported repaglinide tablets in healthy volunteers. Methods： Twenty two healthy male volunteers were randomized into A and B groups. A single dose (4 mg) of domestic and imported repaglinide tablets were given respectively according to an open 2-way crossover study design. The washout period was 1 week. Plasma concentrations of repaglinide were determined by HPLC method. Results：The pharmacokinetic parameters of domestic and imported drugs were as follows: t1/2 were(0.86±0.24) and (0.83±0.31) h；tmax were( 0.79±0.37) and (0.75±0.41) h；cmax were (52.43±20.92) and (53.32±24.94) μg/L. AUC0-t were (79.87±36.48) and (74.95±30.57) μg*h*L-1，respectively. The relative bioavailability of domestic formulation was (106.55±16.15)%. Conclusion： The results of variance analysis and two one-side t test show that 2 formulations are of bioequivalence.

Objective To construct a fusion protein that used for treatment of resistance and palindromia in leukemia and studied its biological activity. Methods IL-3 and LP gene fragments were amplified by PCR. After enzymatic digestion and T4 ligation, the fusion gene was cloned into expression vector pAYZ. The product was purified by exchange chromatography and anti-Etag affinity chromatography. IL3-G4SLP fusion protein was analyzed by SDS-PAGE and Western blot. Protein biological activity was detected by FACS. Results The fusion protein was expressed as soluble protein by E.Coli 16C9. The protein expression level was about 1 mg/L, its purity was over 95 %, and the expression level was about 1 mg/L. The fusion protein can combined specificely with CD123 on leukemia stem cells. Conclusion Fusion protein IL-3-G4S-LP can target on leukemia stem cells and maybe as a potential drug used for treatment of resistance and palindromia in leukemia.

BACKGROUND:Both acupuncture and moxibustion and drug ale effective methods to treat simple obesity.Whether electroacupuncture is different from sibutramine to affect adipocyte products in obese organisms?OBJECTIVE:To observe the different effects of electroacupuncture and sibutramine on adipocyte produces in obesity rats and to investigate the mechanism of weight reduction by acupuncture and moxibustion.DESIGN:Layering-randomized controlled study.SETTING:Laboratory of Acupuncture and Pharmacology.Nanjing University of Chinese Medicine.MATERIALS:12045-day-old male SD rats were provided by Shanghai Experimental Animal Center.The experiment was in accordance with animal ethics standards.Sibutramine hyrdrochloride capsule was made in Fuling Pharmaceutical Factory of Taiji Group(batch number:X20010279).Electro-acupuncture apparatus(LH402A acupoint neutoelectrical stimulation equipment)was made in Beijing Huawei Chanye Developing Company.METHODS:This study was performed at the Laboratory of Acupuncture and Pharmacology,and Expefimental Animal Center,Nanjing University of Chinese Medicine from October 2004 to November 2006.①100 male SD rats underwent high-fat diet.Fifty-four alimentary obesity rats were randomly divided into electroacupuncture group,sibutramine group and obesity group.wim 18 rats in each group.Another 18 rats were regarded as a normal group.②Rats in the electroacupuncture group were given electrical stimulation(2/15 Hz,4 mA)at lateral Housanli and Neiting acupoints,contralateral alternation every other day.Rats were fixed with self-made binding instrument,and rats maintained a consciousness but not an intense struggle.The electricai stimulation lasted for 15 minutes every day,one day was an interval every 6 days.and the electroacupuncture was given for 49 days and 42 times in total.Rats in the sibutramine group were ingragastrically administrated with 0.2 g/L sibutramine hydrochloride(2.0 mg/kg/d).Rats in the control group and obesity groups were fixed the same as electroacupuncture group but not given electrical stimulation.MAIN OUTCoME MEASURES:①Obese marker:To detect body mass,body length,weight reduction rate and body mass/body fat mass,and to measure total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and triacylglycerol (TG)with biochemical chromatometry;②insulin sensitivity index:To measure fasting blood glucose,insulin and insulin sensitivity index with enzyme-linked immunosorbent assay;③adipocyte secreting regulatory substance level:To measure serum resistin,leptin,adiponectin,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and its soluble receptor level with enzyme-linked immunosorbent assay.RESULTS:Among 120 rats,54 alimentary obesity rat models and 18 normal rats were included in the final analysis.①Obesemarker:Bodymass,bodyfatmass,cholesterol and TG levels in the obesity group were significantly higher than in the normal group(P＜0.01).Body mass,body fat mass,body mass/body fat mass,cholesterol and TG levels in the electroacupuncture group were significantly lower than in the obesity group(P＜0.01).TG level in the sibutramine group was significantly lower than in the obesity group(P＜0.01).Weight reduction rate in the electroacupuncture group was significantly higher than in the sibutramine group(P＜0.01).Body mass/body fat mass in the electroacupuncture group was significantly lower than in the sibutramine group(P＜0.01).②Insulin sensitivity:Blood glucose and serum insulin levels in the obesity group were significantly higher than in the normal group,and insulin sensitivity index was significantly lower than in the normal group(P＜0.01).Blood glucose and insulin levels in the electroacupuncture and sibutramine groups were significantly lower than in the obesity group,but insulin sensitivity index was significantly higher than in the obesity group(P＜0.01).③Adipocyte secreting regulatory substance level:Adiponectin in the electroacupuncture group was significantly higher than in the obesity group (P＜0.01).Resistin and TNF-αin the electroacupuncture group was significantly lower than in the obesity grollp(P＜0.01).Resistin level in the sibutramine group was significantly lower than in the obesity group(P＜0.01).CONCLUSION:The effect of electroacupuncture on abnormally secretary products of adipose tissues in obesity rats is superior to the effect of sibutramine.This may be one of important mechanisms of weight reduction by acupuncture and moxibustion,and prevention and cure of obesity and its related diseases.

Aim To construct and express anti-CD20Fab-LDP,generate anti-CD20Fab-LDM and identify its biological activity.Methods PCR and overlapping PCR were used to construct anti-CD20Fab-LDP.DNA sequence was analyzed by the Terminus of Dideoxy Nucleotide.The product was purified by affinity chromatography and analyzed by Western blot and its antigen-binding activity was examined by FACS.Specific killing activity in vitro of anti-CD20Fab-LDM was analyzed by MTT.Results The data of DNA sequence showed that anti-CD20Fab-LDP was correct.The fusion protein was recovered in high yield(up to 4 mg·L~(-1))after proteinG purification.The fusion protein could bind to Raji cells(CD20+),and similar affinity data were obtained with anti-CD20Fab.Anti-CD20Fab-LDP showed potent cytotoxicity to Raji cells with IC_(50) values of 0.9×10~(-10) mol·L~(-1).Conclusions Anti-CD20Fab-LDP with high level expression was successfully obtained and could bind to Raji cells cells.Anti-CD20Fab-LDM showed specific killing activity to Raji cells in vitro.

Objective To investigate the relationship between the urinary albumin excretion (UAE) and serum uric acid in general population. Methods The study participants were derived from the epidemiological study on the association of metabolic syndrome and chronic kidney disease (CKD) in Pinggu district, Beijing. A total of 992 participants (463 men and 529 women) aged from 30 to 75 years were enrolled in this study. For each participant, UAE, serum uric acid, serum creatinine, and serum lipids were detected and other potential risk factors for CKD were surveyed. Results ( 1 ) The frequencies of microalbuminuria, macroalbuminuria and hyperuricemia were 12.9% , 1.8% and 4.3% respectively. The persons with hyperuricemia had significantly higher frequency of albuminuria than those without hyperuricemia (37. 2% vs 13. 7% , P ＜0. 01). (2) The participants were divided according to the quartiles (25% , 50% , 75% ) of serum uric acid level, and the frequencies of albuminuria in males were 13. 2% , 13. 9% , 17. 2% and 25.4% , while those in females were 8. 4% , 6. 2% , 9. 6% and 24. 8%. ( 3 ) Multivariate logistic regression analysis showed, hyperuricemia was significantly associated with albuminuria in females (OR =2. 31, 95% CI 1. 15-4. 68; P=0.02), but not in males. If the persons with reduced renal function were excluded, similar result still could be gained. Conclusions The prevalence of albuminuria increases gradually with uric acid elevation. Serum uric acid is an independent risk factor of elevated UAE, especially in females.