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Population pharmacokinetic model of valproate and prediction of valproate serum concentrations in children with epilepsy

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Acta Pharmacologica Sinica 2004年第12期25卷 10-17页

作者： De-chun JIANG, Li WANG2.Department of Pediatrics, peking university {2. Hospital, TherapeuticDrug Monitoring and Clinical Toxicology, Center of peking university, Beijing 100034, China Department of Pediatrics Peking University First Hospital Therapeutic Drug Monitoring and Clinical Toxicology Center of Peking University 北京 100034

AIM: Using sparse data of valproate (VPA) serum concentrations to build a population pharmacokinetic (PPK) model of VPA in Chinese children with epilepsy and to predict serum concentrations for new patients using a Bayesian approach. METHODS: Two hundred epileptic children, whose VPA serum concentrations were collected, were divided randomly into two groups (A and B, n=100 each). The PPK parameter values of group A were calculated to establish a PPK Model by using the NPEM Program of USC*PACK software. Based on it, VPA serum concentrations of group B were predicted with the Bayesian Fitting Program of the USC*PACK software. To assess the accuracy and precision of prediction, a paired-comparisons t-test was run between predicted and ob- served concentrations, and then the mean prediction error (MPE), mean square prediction error (MSPE), root mean square prediction error (RMSPE), and coincidence rates for different percentages of prediction error were all calculated. RESULTS: Optimum PPK parameters were: Ka, 2.52.±2.743 h-1; Vs, 0.32.±0.496 L/kg; and Kel, 0.0438±0.0384 h-1. For group B, there was no significant difference between predicted and observed concentrations. MPE was -0.43 mg/L, MSPE was 115.40 (mg/L)2. and RMSPE was 5.47 mg/L. The coincidence rates for percent- ages of prediction error, which were less than 5 %, 10 %, 15 %, 2. %, 2. %, and 30 %, were 62.%, 74 %, 82.%, 85 %, 89 %, and 93 %, respectively. CONCLUSION: A PPK model of VPA in epileptic children was successfully established. Based on it, VPA serum concentrations can be predicted accurately with a Bayesian approach.

关键词： pharmacokinetics valproic acid epilepsy Bayes theorem USC*PACK software

Changes of brain neuropeptide Y and its receptors in rats with flurazepam tolerance and dependence

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Acta Pharmacologica Sinica 2005年第11期26卷 1290-1296页

作者： Li-ping ZHANG, Li WANG~2.Department of Pediatrics, peking university {2. Hospital, Beijing 100034, China DepartmentofPediatrics PekingUniversityFirstHospitalBeijing100034China

Aim: Anticonvulsant tolerance and dependence are two obstacles that restrict the clinical use of benzodiazepines (BDZ). In order to explore the mechanism of these two adverse reactions, changes of neuropeptide Y (NPY) and its receptors in the hippocampus of rat models, in relation to flurazepam (FZP, a member of BDZ) tolerance and dependence, were investigated. Methods: The mRNA of preproNPY and its receptors (Y1, Y2. and Y5) in the hippocampus were determined by competitive RT-PCR, and the distribution of NPY in the hippocampus was examined by immunohistochemistry. Results: A decrease of preproNPY mRNA in the hippocampus was found in tolerant and dependent rats. The level of preproNPY mRNA in the hippocampus was reversely correlated with the degree of tolerance and dependence, measured by the threshold of pentylenetetrazol-induced seizures. Immunohistochemistry indicated a decrease of NPY-immunoreactive material in neurons of the CA1, CA3, and dentate gyrus regions of both tolerant and dependent rats. The mRNA of NPY receptors Y,and Y5decreased in tolerant rats but did not change in dependent rats. The mRNA of NPY receptor Y2.ncreased in tolerant rats but decreased in dependent rats. Conclusion: A decrease of NPY in the hippocampus might be involved in anticonvulsant tolerance and dependence following long-term treatment with FZP. Y,, Y2. and Y5mRNA were also altered in FZP tolerance and dependence.

关键词： benzodiazepines neuropeptide Y flura zepam

Density-functional formula for strongly correlated systems

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Progress in Natural Science:Materials International 2005年第5期15卷 395-401页

作者： WANG Huaiyu1*, HAN Rushan2.and CHEN Nanxian1(1. Department of Physics, Tsinghua university, Beijing 100084, China 2. Department of Physics, peking university, Beijing 100871, China) Department of Physics Tsinghua University Beijing 100084 China Department of Physics Peking University Beijing 100871 China

Density functional method is applied for strongly correlated systems. Based on the assumption that the systems are composed of electrons in singly-occupied orbitals and those in doubly-occupied orbitals, a set of self-consistent equations are obtained by standard variation procedure. The equations consist of two parts. One part is to solve the wave functions of the electrons in singly-occupied orbitals and the other is to solve the wave functions of the electrons in doubly-occupied orbitals. The physical meanings of the terms appearing in the equations are discussed.

关键词： density-functional theory strongly correlated systems doubly-occupied orbital two-particle wave function self-consistent equations.

Interaction between hydrogen sulfide/cystathionine γ-lyase and carbon monoxide/heme oxygenase pathways in aortic smooth muscle cells

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Acta Pharmacologica Sinica 2006年第12期27卷 1561-1566页

作者： Hong-fang JIN~2.Jun-bao DU~(2.4)Xiao-hui LI~2.Yan-fei WANG~2.Yin-fang LIANG~2.Chao-shu TANG~3 2.Department of Pediatrics,peking university {2. Hospital,Beijing 100034,China 3 Institute of Cardiovascular Research,peking university {2. Hospital,Beijing 100034,China Department of Pediatrics Peking University First Hospital Beijing 100034 China.

Aim:To investigate the interaction between hydrogen sulfide（H2.）/cystathion-ine γ-lyase（CSE）and carbon monoxide（CO）/heme oxygenase（HO）pathways inaortic smooth muscle cells（ASMC）.Methods:The ASMCs were divided into thefollowing groups:（1）the control group;（2.the zinc protoporphyrin（ZnPP）2.μmol/L group;（3）the propargylglycine（PPG）2.mmol/L,4 mmol/L and 10 mmol/Lgroups;and（4）the sodium hydrosulfide（NariS）1×10-5mol/L,1×10-4mol/L and1×10-3mol/L *** of the groups was further divided into 6h,12.,18hand 2.h *** CO level,represented by carboxyhemoglobin（HbCO）content was measured using a spectrophotometric method and H2. content wasdetected by a sensitive electrode *** and HO-1 expressions were de-tected by Western ***:The H2. content in the medium and CSEexpression by ASMC were markedly increased by ZnPP compared with the con-trol *** content in the medium and HO-1 expression by the ASMCstarted strengthening following 2.h treatment with PPG at 2.mmol/L,but werefurther strengthened following 18h and 2.h treatment with PPG at 4 mmol/Lcompared with the controls（P2. ***,NariS at 1×10-5mol/L and 1×10-4mol/Ldecreased the HbCO level in the medium and HO-1 expression by the ASMC after6h and 12. treatment,while NariS at 1×10-3mol/L decreased them at all timepoints of the ***:The results suggested that endogenousCO/HO and H2./CSE pathways inhibited each other in ASMC under physiologi-cal conditions.

关键词： hydrogen sulfide cystathionine γ-lyase carbon monoxide heme oxygenase

A novel endorectal RF coil for high resolution MRI and spectroscopy of the prostate

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Progress in Natural Science:Materials International 2005年第5期15卷 472-476页

作者： ZHANG Hongjie 1,2. SONG Xiaoyu1, WANG Xiaoying3, XU Pingfang1 and BAO Shanglian1*(1. Beijing Key Laboratory of Medical Physics & Engineering, peking university, Beijing 100871, China 2. Navy General Hospital, Beijing 100037, China 3. peking university first Hospital, Beijing 100034, China) Beijing Key Laboratory of Medical Physics & Engineering Peking University Beijing 100871 China Navy General Hospital Beijing 100037 China peking university {2. Hospital Beijing 100034 China

The diagnosis of prostate diseases by magnetic resonance imaging (MRI) in vivo is sometimes difficult for the lower signal to noise ratio (SNR). To increase the SNR of the prostate image, we designed a RF coil that can be inserted into rectum and was named endorectal coil. The properties of RF coil were evaluated using a network analyzer. Moreover the images and spectroscopy of a special phantom were acquired and the results were compared to those of the commercial TORSO coil (G.E. Medical Systems, USA). Our coil gave a significantly higher SNR at the region of interest (ROI). The achieved high local SNR and resulting high spatial resolution would add more anatomic and biochemical information to the diagnosis of prostate diseases.

关键词： MRI RF coil endorectal coil.

The regular representation and regular covariant representation of crossed products of Woronowicz C^(*)-algebras

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Science China Mathematics 2005年第9期48卷 1245-1259页

作者： ZHANG Xiaoxia~(1,2. & GUO Maozheng~(1,3) 1. School of Mathematical Sciences,peking university,Beijing 100871,China 2. Department of Mathematics,Yantai university,Yantai 2.4005,China 3. LMAM,peking university,Beijing 100871,China School of Mathematical Sciences Peking University Beijing China Department of Mathematics Yantai University Yantai China LMAM Peking University Beijing China

In this paper,it is shown that the regular representation and regular covariant representation of the crossed products A×α G correspond to the twisted multiplicative unitary operators,where A is a Woronowicz C~*-algebra acted upon by a discrete group ***,it is also shown that the regular covariant C~*-algebra is the Woronowicz C~*-algebra which corresponds to a multiplicative ***,an explicit description of the multiplicative unitary operator for C(SU_q(2. )×α (?) is given in terms of those of the Woronowicz C~*-algebra C(SU_q(2. ) and the discrete group G.

关键词： multiplicative unitary operator, Woronowicz C*-algebra, crossed product.

Nitric oxide modulates hypoxic pulmonary smooth muscle cell proliferation and apoptosis by regulating carbon monoxide pathway

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Acta Pharmacologica Sinica 2007年第1期28卷 28-35页

作者： Yan-fei WANG~2.Hong TIAN~2.Chao-shu TANG~(3,4) Hong-fang JIN~2.Jun-bao DU~(2.4,5)2.Department of Pediatrics,peking university {2. Hospital,Beijing 100034,China 3 Institute of Cardiovascular Diseases,peking university {2. Hospital,Beijing 100034,China,4 Key Laboratory of Molecular Cardiovascular Diseases,Ministry of Education,Beijing 100034,China DepartmentofPediatrics PekingUniversityFirstHospitalBeijing100034China InstituteofCardiovascularDiseases PekingUniversityFirstHospitalBeijing100034China KeyLaboratoryofMolecularCardiovascularDiseases MinistryofEduc

Aim:To explore the role of carbon monoxide(CO)in the regulation of hypoxicpulmonary artery smooth muscle cell(PASMC)proliferation and apoptosis bynitric oxide(NO).Methods:PASMC of Wistar rats was cultured in vitro in thepresence of a NO donor,sodium nitroprusside,or an inhibitor of heine oxygenase(HO),zinc protoporphyrin-IX,or under both normoxic and hypoxic *** and carboxyhemoglobin in PASMC medium were detected *** proliferating and apoptotic percentage of PASMC wasmeasured by flow *** expression of HO-1 mRNA in PASMC wasanalyzed by fluorescent real-time quantitative PCR,and the proliferating cell nuclearantigen and caspase-3 were examined by immunocytochemical ***:The results showed that hypoxia suppressed NO generation from PASMC,whichpromoted hypoxic PASMC proliferation and induced ***,hy-poxia induced HO-1 expression in PASMC and promoted CO production fromPASMC,which inhibited PASMC proliferation and regulated PASMC *** upregulated the expression of HO-1 mRNA in hypoxic PASMC;NO also inhib-ited proliferation and promoted apoptosis of hypoxic PASMC,possibly by regu-lating the production of ***:The results indicated that CO couldinhibit proliferation and regulate apoptosis of PASMC,and NO inhibited prolifera-tion and promoted apoptosis of hypoxic PASMC,possibly by regulating the pro-duction of CO.

关键词： hypoxia proliferation apoptosis carbon monoxide nitric oxide

Paleoceanographic evolution recorded in the northern South China Sea since 4 Ma

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Science China Earth Sciences 2005年第12期48卷 2166-2173页

作者： HUANG Baoqi1,2. JIAN Zhimin2.& WANG Pinxian2.1. School of Earth and Space Sciences, peking university, Beijing 100871, China 2. Laboratory of Marine Geology, Tongji university, Shanghai 2.0092. China School of Earth and Space Sciences Peking University Beijing China Laboratory of Marine Geology Tongji University Shanghai China

Upper water structure over the last 4 million years in the northern South China Sea (SCS) was reconstructed by sea surface temperature (SST) and primary productivity estimated by changes in the abundance of planktonic foraminifer, planktonic foraminifer transfer function, and the accumulation rate of benthic foraminifera. Results of SST and primary productivity show that SST gradually decreased since 4 Ma, but differential seasonal temperature and primary productivity increased in steps mainly at about 3.1, 2.7, 2.1, 1.6, 0.9 and 0.5 Ma. Comparison with tectonics and orbital variations indicates that phased rising of the Tibet since 3.6 Ma, closing of Panama and Indonesian seaways, and orbital changes were responsible for the changes of upper water structure in the SCS, respectively.

关键词： northern South China Sea, upper water structure, Late Pliocene, planktonic foraminifer, ODP 1146.

THE OPTICALLY PUMPED CESIUM BEAM FREQUENCY STANDARD AT peking university

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计量学报 1991年第S1期12卷 12-16页

作者： Wang Yiqiu and Yang Donghai(peking university,Beijing 100871,P.R.China)

An optically pumped cesium beam frequency standard with bias-saturated absorption lock of laser diodes has been built up at peking *** frequency stability of 1.2.10-11/t1/2.was obtained.A new idea of sharp angle incidence of probing laser beam has been tested experimentally and fairly good results were *** improvements are discussed.

关键词： pumped optically fairly saturated peking probing sharp locked BEAM automatically