1.Impact of cytochrome P450 CYP2C9 variant allele CYP2C9 * 3 on the pharmacokinetics of glibenclamide and lornoxicam in Chinese subjects.
Yi-Fan ZHANG ; Xiao-Yan CHEN ; Ying-Jie GUO ; Da-Yong SI ; Hui ZHOU ; Da-Fang ZHONG
Acta Pharmaceutica Sinica 2005;40(9):796-799
AIMTo investigate the impact of CYP2C9 * 3 on the pharmacokinetics of glibenclamide and lornoxicam.
METHODSCYP2C9 * 3 was measured in 83 non-related Chinese subjects by PCR-RFLP. The pharmacokinetics of lornoxicam and glibenclamide were investigated in 18 subjects (7 with CYP2C9 * 1/* 3 genotype and 11 with * 1/* 1 genotype). Glibenclamide and lornoxicam in plasma were determined by the sensitive liquid chromatography-tandem mass spectrometry, separately.
RESULTSAfter a single oral dose of 2.5 mg glibenclamide, C(max) was (70.0 +/- 11.5) microg x L(-1) in CYP2C9 * 1/ * 3 subjects and (51.9 +/- 12.3) microg x L(-1) in * 1/ *1 subjects. AUC(0-infinity) were (435 +/- 47) vs (287 +/- 95) microg x h x L(-1) (in * 1/ * 3 vs * 1/ *1 subjects), and CL/F were (96 +/- 9.3) vs (160 +/- 51) mL x min(-1), respectively. Statistic analysis results indicated that glibenclamide AUC(0-infinity) was significantly higher (1.5-fold) and subsequently CL/F was significantly lower (40%) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.01). After a single oral dose of 8 mg lornoxicam, C(max) was (1.54 +/- 0.24) mg x L(-1) in CYP2C9 * 1/ * 3 subjects and (1.19 +/- 0.37) mg x L(-1) in * 1/ * 1 subjects. AUC(o-infinity were (14.9 +/- 2.2) vs (6.92 +/- 1.48) mg x h x L(-1) (in * 1/ *3 vs * 1/ * 1 subjects), and CL/F were (9.1 +/- 1.2) vs (20.1 +/- 4.6) mL x min(-1), respectively. Statistic analysis results indicated that lornoxicam AUC(0-infinity) was significantly higher (2. 2-fold) and subsequently CL/F was significantly lower (55% ) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.001).
CONCLUSIONCYP2C9 * 3 greatly affects both the pharmacokinetic profiles of glibenclamide and lornoxicam. The elimination of these drugs significantly decreased in subjects with CYP2C9 * 1/ * 3 genotype, especially lornoxicam.
Adult ; Alleles ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacokinetics ; Area Under Curve ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; China ; Cytochrome P-450 CYP2C9 ; Genotype ; Glyburide ; pharmacokinetics ; Humans ; Hypoglycemic Agents ; pharmacokinetics ; Male ; Piroxicam ; analogs & derivatives ; pharmacokinetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length
2.Studies on TLC fingerprint of flavonoids in rhizome of Polygonatum odoratum.
Xian-guo YANG ; Si-bao CHEN ; Shi-lin CHEN ; Da-jian YANG ; Ta-si LIU
China Journal of Chinese Materia Medica 2005;30(2):104-106
OBJECTIVETo study the thin layer chromatographic (TLC) fingerprint of flavonoid constituents from Polygonatum odoratum, to set up the identification protocol of the herbal and provide scientific information for its quality control.
METHODThe ethanol extracts were separated on silica gel G precoated plate with a mixture of toluene-ethylacetate-formic acid (5:4:1) as the mobile phase. The spots were visualized with ammonia vapor, then were examined under ultraviolet light (365 nm). The plate was scanned at wavelengths of lambdaR = 500 nm, lambdaS = 280 nm.
RESULTA fingerprint of flavonoids of P. odoratum, with 10 specific fluorescent spots while examined under ultraviolet light, was set up.
CONCLUSIONThe method can be used for quality control of P. odoratum.
Chromatography, Thin Layer ; methods ; Flavonoids ; analysis ; chemistry ; Plants, Medicinal ; chemistry ; Polygonatum ; chemistry ; Quality Control ; Rhizome ; chemistry
4.GVHD Following Autologous Peripheral Blood Stem Cell Trasplantation Reduced Malignancy Relapse
Da-Si GUO ; Xiao-Lin LI ; Su ZHANG ; Jie FU ; Yang YANG ; Yue YIN
Journal of Experimental Hematology 2001;9(3):287-288
Administration of the immunosuppressive drug cyclosporine (CSA) after autologous peripheral blood stem cell transplantation (APBSCT) induces a systemic auto-immune syndrome resembling graft-versus-host disease (GVHD), this syndrome termed autologous GVHD has significant antitumor activity, it can reduce the incidence of tumor relapse after APBSCT. The antitumor effect of this auto-aggression syndrome can be enhanced by the administration of gamma-interferon (gamma-IFN). Five consecutive patients who received APBSCT received therapy inducing autologous GVHD. Intravenous administration of CSA [1 mg/(kg.d) for 28 days] was begin on the day of transplantation. gamma-interferon (0.025 mg/m(2) qod) was administered sub-cutaneously from days 7 throngh 28 after transplatation. Results showed that four of five occured autologous GVHD-skin demage, five in control didn't occur autologous GVHD. The relapse rate of the treated cases was 20% (1/5) versus 60% (3/5) of the control, and the median survival time of the treated cases was 20 (4 - 30) months versus 10 (2 - 20) months of the control. The data indicates that autologous GVHD results in low relapse rate of the patients rececving APBSCT.
5.Preparation of paclitaxel-loaded polybutylcyanoacrylate nanoparticles.
Ru-da CHEN ; Fei REN ; Guo-feng LI ; Si-jia LIU
Journal of Southern Medical University 2010;30(4):763-766
OBJECTIVETo evaluate the effect of different preparation methods on the encapsulation efficiency (EE) and drug loading (DL) of paclitaxel-loaded polybutylcyanoacrylate nanoparticles (PTX-PBCA-NPs) and optimize the preparation of PTX-PBCA-NPs.
METHODSWith DL and EE as the major indexes, the qualities of PTX-PBCA-NPs produced by the interfacial polymerization and emulsion polymerization method were compared. The optimized prescription was obtained by orthogonal design.
RESULTSThe ranges of EE of PTX-PBCA-NPs with the two methods were both 94.39%-99.23%. The highest DL with interfacial polymerization was (1.07-/+0.03)%, as compared to (0.86-/+0.01)% with emulsion polymerization. The optimized preparation conditions resulted in the mean size of PTX-PBCA-NPs of 235.6 nm, DL of 0.80%, and EE of 95.71%.
CONCLUSIONThe EE of PTX-PBCA-NPs prepared by the above two methods is consistent with the requirement of the Pharmacopoeia of China, and PTX-PBCA-NPs containing higher DL can be obtained via interfacial polymerization.
Delayed-Action Preparations ; chemical synthesis ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Enbucrilate ; chemistry ; Nanoparticles ; chemistry ; Paclitaxel ; administration & dosage ; Polymerization
6.Effects of storage time on magnolol and honokiol contents in bark of Magnolia officinalis.
Da LV ; Jin-ping SI ; Zai-kang TONG ; Bao-lin GUO ; Yan-feng JIANG ; Yu-qiu ZHU
China Journal of Chinese Materia Medica 2008;33(17):2087-2089
OBJECTIVETo reveal the relationship between the storage time of the bark of Magnolia officinalis and the content of phenols in it, and lay a theoretical foundation for the harvest, processing, management and storage.
METHODThe contents of magnolol and honokoiol in 15 bark samples, collected from the main producing areas in China, were determined in the time of freshly harvest and 3 and 10 years after respectively by HPLC method.
RESULTIt showed that within a certain period of time, bark storage was favorable to conversion and accumulation of phenols, that the content of magnolol tended to increase from year 0 to year 3, then followed by slight decrease with years on account of volatilization of phenols, but was still higher when the bark was stored for 10 years than that that when the bark was freshly harvested, and the content of honokoiol still tended to increase when the bark had been stored for 10 years.
CONCLUSIONThe phenols in bark of M. officinalis is quite stable and the bark can be stored for 10 years or longer.
Biphenyl Compounds ; analysis ; Drug Storage ; methods ; Drugs, Chinese Herbal ; chemistry ; Lignans ; analysis ; Magnolia ; chemistry ; Plant Bark ; chemistry ; Time Factors
7.Prospective study of coverage of left subclavian artery during thoracic endovascular aortic repair in a single center.
Yi SI ; Wei-guo FU ; Yu-qi WANG ; Xin XU ; Da-qiao GUO ; Bin CHEN ; Jun-hao JIANG ; Jue YANG ; Zhen-yu SHI ; Ting ZHU ; Yun SHI ; Zhi-hui DONG
Chinese Journal of Surgery 2009;47(24):1868-1872
OBJECTIVETo describe observation of security and availability of covering left subclavian artery during thoracic endovascular aortic repair (TEVAR) in follow-up.
METHODSFrom December 2007 to December 2008, 111 consecutive patients received stent grafts to treat lesions involving thoracic aorta. According to the covering of left subclavian artery, four groups including total covering (TC), less-than 50% covering (LTC), more-than 50% covering (MTC) and non-covering (NC) were formed. Difference of blood pressure between two upper extremities was required before TEVAR and 1st, 3rd, 5th, 30th day after TEVAR. Patients were evaluated postoperatively and at follow-up for stroke as well as symptoms of paraplegia, hemiparalysis or left upper extremity claudication.
RESULTSFifty-five (49.6%), 18 (16.2%), 7 (6.3%) and 31 (27.9%) cases were divided into TC, LTC, MTC and NC groups, respectively. Difference of blood pressure between TC and the 3 latter groups were significantly different (P<0.01). Complications appeared as followed during one week after TEVAR: 13 patients in dizziness, among which 5 patients suffered from amaurosis and spotted vision, and 7 patients in left upper extremity claudication. No stroke, paraplegia or hemiparalysis in TC. Thoracic aortic lesions were successfully excluded in all patients.
CONCLUSIONSIntentional coverage of left subclavian artery to obtain an adequate proximal landing zone during TEVAR is safe and well-tolerated. But it may be managed expectantly with some exceptions for further lasting efficacy.
Aorta, Thoracic ; surgery ; Aortic Aneurysm, Thoracic ; surgery ; Blood Vessel Prosthesis Implantation ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stents ; Subclavian Artery ; surgery ; Treatment Outcome
8.Study on growth of height among students during their adolescence in Zhongshan, Guangdong
Ci-He CAI ; Jun MA ; Zhi-Da HUANG ; Bin DONG ; Si-Zhe HUANG ; Li-Mei WANG ; Xiao-Ying GUO ; Feng-Hua LI ; Chao-Jun CHEN
Chinese Journal of Epidemiology 2012;33(7):717-721
Objective To discuss characteristics of height growth such as Peak Height Velocity (PHV) and Age at Peak Height Velocity (PHA) during adolescence,and to compare the results with other research findings.Methods Primary and middle school students' annual physical examination data of Zhongshan in 2005-2010 was used.The height velocity by age,PHV,PHA,height velocity by PHA were calculated.Results The average peak height velocity boys was ( 10.03 ± 1.67 ) cm/yr.and that of the girls was ( 8.39 ± 1.05 ) cm/yr.Both findings were close to the results from previous similar findings.The average age at which peak height velocity reached 12.28± 1.30 years for boys and 10.78 ± 1.04 years for girls,both lower than the previous findings.The correlation coefficients,between height level and PHA were -0.357 (P<0.001) for boys and -0.338 (P<0.001) for girls.Conclusion The height levels were positively related to the height velocity before PHA.The Zhongshan students' PHA was lower than the Beijing,Shanghai and Shenyang students,also lower than American and Britain students',but their PHVs were similar.
9.Over-expression in Escherichia coli and characterization of apolipoprotein AI.
Man-Sheng DING ; Wen-Feng MA ; Mei-Fang ZHANG ; Da-Tao LIU ; Mei-Jin GUO ; Ying-Ping ZHUANG ; Ju CHU ; Si-Liang ZHANG ; Bang-Qiang GONG
Chinese Journal of Biotechnology 2005;21(2):198-203
Apolipoprotein AI (apo AI), the major protein component of human high-density lipoprotein (HDL), is a single-chain polypeptide of 243 amino acids. Several epidemiological studies have shown that the plasma concentrations of HDL has the role of reverse cholesterol transport (RCT) and inversely correlated with the incidence of coronary artery disease. Because apo AI lacks post-translational modifications, it is convenient to express human apo AI in Escherichia coli expression system. However, there is a poor stability of the mRNA and the apo AI protein in E. coli, it is difficult to express mature apo AI in recombinant bacteria, moreover, even as a fusion protein, apo AI is still sensitive to degradation and can not be cleaved efficiently from the fusion tags. In contrast, proapolipoprotein AI (proapo AI, having an additional polypeptide containing the amino acids Arg-His-Phe-Trp-Gln-Gln at the amino-teminal of the mature protein) proved stable and undegraded in Escherichia coli, and therefore, in this research, an expression system of E. coli including a plasmid of P(R)P(L) tandem promoter was adapted to produce proapo AI. Furthermore, site-directed mutagenesis of the proapo AI cDNA was performed to generate a Clu8Asp mutation in the amino-terminal sequence of proapo AI which created an acid labile Asp-Pro peptide bond between amino acid 8 and 9, and permitted specific chemical cleavage to remove pro-peptide. After inducing with a shift of temperature, yields of recombinant proapo AI achieved about 40% of total cell protein and the recombinant proapo AI expressed proved as a form of inclusion body in cells, so protein need to renature. First of all, the protein was dissolved in buffer with denaturant, and renaturation was carried out on a hydrophobic interaction column (Phenyl Sepharose), ion-exchange chromatography and gel-filtration chromatography were then used to further purify the protein. The purified recombinant apo AI was detected by a set of tests including Western-blotting, Circular dichroism spectra and lipid-binding test, the results shown that recombinant apo AI has similar structural and lipid-binding properties identical to those of native plasma apo AI, which facilitates further research and application.
Apolipoprotein A-I
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biosynthesis
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genetics
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Chromatography, Ion Exchange
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methods
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Escherichia coli
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genetics
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metabolism
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Humans
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Mutagenesis, Site-Directed
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Mutation
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Protein Precursors
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biosynthesis
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genetics
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Recombinant Proteins
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biosynthesis
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genetics
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isolation & purification
10.Application of cluster randomization method on typhoid Vi vaccine trails.
Bai-qing DONG ; Jin YANG ; Zhen-zhu TANG ; Hong-hui YANG ; Jun ZENG ; Jie ZHANG ; Ming-liu WANG ; Gui-chen LIANG ; Guo-ai SI ; Cui-yun LI ; Da-bin LIANG ; He-zhuang LIAO ; Rion Leon OCHIAI ; Ali MOHAMMAD ; Camilo J ACOSTA ; John CLEMENS
Chinese Journal of Epidemiology 2005;26(2):97-100
OBJECTIVETo describe the design and application of cluster randomized controlled method on typhoid Vi vaccine trial, and to assess the effect of implementation.
METHODSSimple size calculation of cluster-randomized trial was used to determine the sample size of the two groups and a vaccination campaign was conducted. The study group was given typhoid Vi vaccine and the control group was given meningococcal A vaccine.
RESULTSAccording to sample size calculation, a total sample of 96,121 participants was required and the study areas were divided into 108 clusters. In practice, 53 study clusters with 44,054 participants and 54 control clusters with 48,422 participants were stratified and matched according to size, location (urban or rural), characteristics (school, department, factory, demography) were randomized respectively. Confounding factors of two groups including age, sex, resident area, income, level of education were compared. It was found that the ratio of all confounding factors between the two groups were comparable and balanced.
CONCLUSIONConfounding factors can be better controlled between study group and the control group by applying cluster-randomized method on vaccine trail which enabled the intervention to be more scientifically evaluated; The implementation of cluster randomization trial was simple and easy to be accepted.
Adolescent ; Adult ; Child ; Child, Preschool ; China ; Cluster Analysis ; Female ; Humans ; Male ; Mass Vaccination ; organization & administration ; Middle Aged ; Polysaccharides, Bacterial ; immunology ; Typhoid Fever ; prevention & control ; Typhoid-Paratyphoid Vaccines ; immunology ; Vaccination