Table of Content

Volume 14 Issue 6
26 June 2009

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Advances in quantitative pharmacology

HUANG Xiao-hui, XIE Hai-tang, SHI Jun, SONG Jian-guo, ZHENG Qing-shan

2009, 14(6):  601-612. 

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Quantitative pharmacology, also termed as pharmacometrics, is the scientific discipline that uses mathematical and statistical methods to quantify the interactions between therapeutic drugs and patients.It increasingly plays a critical role in drug development and pharmacotherapy.Model-based drug development (MBDD)is a paradigm and a mindset which promotes the use of modeling to delineate the path and focus of drug development.The utilization of MBDD remains at an early stage in China, but it is clear that Chinese scientists embrace the discipline, and are keen to apply this methodology to drug development.In this review, we first introduce the definition and developmental history of quantitative pharmacology.Furthermore, we discuss the major areas that the present research focuses and the technological advances in the filed, such as population pharmacokinetics/pharmacodynamics, exposure-response (PK-PD)modeling, clinical trial simulation, novel clinical trial designs, biomarker, disease model, trial model, and M&S methodology.Following that, we give a brief introduction to MBDD.Finally, some challenges that pharmacometrican are currently facing, and the possible solutions are discussed.

Effects of methylamine irisolidone on mitochondrial membrane potential in H₂O₂-induced rat cadiocyte injury

HAO Yan-jie, WANG Yuan-shu, MU Yan-ling, XIE Yan-ying, ZHANG Qiang, ZHOU Ling

2009, 14(6):  613-616. 

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AIM: To investigate the protective effect of methylamine irisolidone(MMI)preconditioning on mitochondrial membrane potential in H₂O₂-induced rat cardiomyocytes injury. METHODS: With the pretreatment of methylamine irisolidone for 12 h in the model of H₂O₂-induced injury, the cell viability was determined by MTT assay, and the morphology change was examined with Wright's staining and Giemsa's staining, and the change of mitochondrial membrane potential was analyzed by flow cytometry. RESULTS: Compared with the normal group, the cell viability of model group was significantly decreased (P<0.01). Pretreated with methylamine irisolidone (0.5, 1, 5, 10 μmol/L)the cell viabilities were increased significantly (P<0.05, P<0.01), but MMI 0.1 μmol/L group had the similar cell viability compared with the model group (P>0.05).Moreover, pretreated with methylamine irisolidone (1, 5, 10 μmol/L)the mitochondrial membrane potential were increased (P<0.05, P<0.01), and 10 μmol/L group reduced the cell morphology injury. CONCLUSION: Methylamine irisolidone can improve the morphology injury of cadiocytes induced by H₂O₂ and increase the mitochondrial membrane potential, which can decrease the cadiocyte apoptosis.

Anti-breast cancer experiment research on heparan sulfate proteoglycan and heparan sulfate proteoglycan without heparan sulfate-glycosaminoglycan chain in vitro

XIE Qiang, JIANG Zhi-wen, ZHU Xiao-guang, LIU Hao

2009, 14(6):  617-623. 

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AIM: To compare the antiproliferative effect and apoptosis-inducing activity by HSPG and HSPG without heparan sulfate chains on human mammary cancer cell MDA-MB-231 in vitro. METHODS: HSPG was isolated and purified, the heparan sulfate chains of HSPG was hydrolyzed by heparitinase1.The changes of two components cell morphology were observed by light microscope, the anti-proliferation of HSPG and HSPG without HS chains was measured by MTT assay, the cell growth curve was drawn and the apoptosis was detected by Annexin V PI double staining and flow cytometry. RESULTS: MCF-7 type HSPG induced the exfoliation and suspension of MDA-MB-231 cells.MTT assay showed that different concentrations of HSPG inhibited MDA-MB-231 cells proliferation in a concentration-dependent manner.There was inhibition effect only in high concentrations of HSPG without HS chains.HSPG induced MDA-MB-231 cells'apoptosis at the early stage, however, 4 mg/mL HSPG without HS chains had some effects on the apoptosis at the early stage. CONCLUSION: HSPG could induce MDA-MB-231 cells' apoptosis at the early stage and distinctly inhibit the growth of MDA-MB-231 cells, the mechanism may be related to HS chains of HSPG.

Effects of Tougu Xiaotong Granula(TXG)-containing serum on proliferation of rabbit chondrocytes in vitro

YE Hong-zhi, LI Xi-hai, LIANG Wen-na, ZHENG Chun-song, CHEN Wen-lie, LIU Xianxiang

2009, 14(6):  624-628. 

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AIM: To investigate the effects of Tougu Xiaotong Granula(TXG)-containing serum on proliferation of rabbit chondrocytes in vitro. METHODS: The chondrocyte was obtained from the arthrodial cartilage of 4-week-old New Zealand rabbit by collagenase Ⅱdigestion, so as to establish the system of chondrocyte culture in vitro.The 3rd passage of chondrocyte in vitro was randomly divided into five groups which were respectively cultured with medium, medium with serum and the high, medium, low doses of TXG-containing serum.After cultured for 24, 48 and 72 hours, the cell cycle changes were detected by the flow cytometry. RESULTS: The high, medium doses of TXGcontaining serum could stimulate the chondrocyte through G₀/G₁ phases into S and G₂/M phases in a time-dependent manner by flow cytometry.Compared with the control and low-dose groups, the proportions of cells in G₀/G₁ phase in the high-and medium-dose groups were significantly lower, meanwhile those in S and G₂/M phases were significantly higher after 48 hours(P<0.05). CONCLUSION: TXG-containing serum could effectively promote the cell proliferation of chondrocytes.

Synergistic protective effects of sesamin in combination with vitamin E on nephropathy in rats with metabolic syndrome

YANG Jie-ren, WU Xiang-qi, ZHOU Yong, HUANG Kai, XIONG Ke-ren, CHEN Guo-xiang

2009, 14(6):  629-636. 

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AIM: To study the renoprotective and synergistic effects of sesamin in combination with vitamin E on nephropathy in rats with the metabolic syndrome. METHODS: Nephropathy of metabolic syndrome in rats was induced by high-fat and high-carbohydrate diet.Sesamin (30 mg·kg^-1·d^-1), sesamin+vitamin E [(15+20) mg·kg^-1·d^-1), sesamin+vitamin E (30+20) mg·kg^-1·d^-1] and vitamin E (20 mg·kg^-1·d^-1) were given to rats with metabolic syndrome at 9th week and lasted for 16 weeks.After 24 weeks, the body weight, left kidney humid weight, blood glucose (BG), blood lipids (BL), systolic blood pressure (SBP), renal function, and indexes of oxygenation and antioxygenation for renal cortex were measured.Pathological changes, collagen deposition and iNOS protein and nitrotyrosine expression of kidney were observed by HE-stain, Masson-stain and immunohistochemical method, respectively. RESULTS: (1) In high-fat and refined-sugar diet group (HFS):the levels of BG, BL, SBP, and MDA, OH^- and NO₂^-/NO₃^-in renal cortex were increased;the activities of T-SOD, CAT and GSH-Px in renal cortex were decreased;the expressions of iNOS protein and nitrotyrosine in kidney were up-regulated;the inflammatory cell infiltration and collagen deposition in renal glomerulus and renal interstitium were severe;the glomerular sclerosis and renal interstitial fibrosis were obvious;the renal function was deteriorated.(2) In sesamin+vitamin E [(30+20) mg·kg^-1·d^-1] group:the decreases in BG, BL, SBP, MDA, OH^- and NO₂^-/NO₃^-in renal cortex were obviously observed;the activities of T-SOD, CAT and GSH-Px in renal cortex were increased;the expressions of iNOS protein and nitrotyrosine in kidney were down-regulated;the inflammatory cell infiltration and collagen deposition in renal glomerulus and renal interstitium were improved;the glomerular sclerosis and renal interstitial fibrosis were reversed;the renal function was ameliorated.The therapeutic effect of sesamin+vitamin E [(30+20) mg·kg^-1·d^-1] surpassed that of using sesamin or vitamin E alone (P<0.01 or P<0.05). CONCLUSION: Sesamin and vitamin E have synergistic antioxidant activity and protective effect against renal disease in metabolic syndrome rats.

Regulatory effect of ligustrazine on the dynamic change of thromboxane/prostacyclin in renal ischemia reperfusion injury rabbits

MAO Chao-ming, CHEN Hui-le, WANG Wan-tie, JIN Ke-ke, QIU Xiao-xiao, XIE Ke-jian

2009, 14(6):  637-641. 

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AIM: To investigate the dynamic change of thromboxane prostacyclin in renal ischemia reperfusion injury rabbits, and approach the regulatory effects of ligustrazine injection on renal ischemia reperfusion injury and its mechanisms. METHODS: Thirty rabbits were divided into three groups randomly:sham operation group (group S), ischemia reperfusion injury group (group IR) and ischemia reperfusion injury plus ligustrazine injection group (group LZ), each group had ten rabbits.The renal ischemia reperfusion injury model of rabbit was established in vivo.The content of thromboxane B₂ (TXB₂), 6-keto-prostaglandin F_1α(6-keto-PGF_1α) were detected in the blood plasma gathered from common carotid artery at times:pre-ischemia, ischemia 1 h, reperfusion 1, 3 and 5 h, the ratio of TXB₂ and 6-keto-PGF_1αwere calculated.The content and the ratio of TXB₂ and 6-keto-PGF_1α in kidney tissue were detected at the end of the experiment. RESULTS: The content of TXB₂ in plasma showed a time-dependent ascensus in group IR during ischemia reperfusion, it was significant higher than that in group S at all time points (all P<0.01).Compared withgroup IR and with group S, the content of TXB₂ in plasma was decreased significantly in group LZ at each time point during ischemia reperfusion (all P<0.01). Compared with group S, there was not different significance for the TXB₂ 6-keto-PGF_1α in group LZ(all P> 0.05).Compared with group IR, it was significant lower in group LZ at each of time point (all P<0.01). Compared with group IR, in group LZ, the TXB₂ level and TXB₂ 6-keto-PGF_1α in kidney tissue were decreased remarkably (all P<0.01), there was no different significances in 6-keto-PGF_1α (P>0.05). CONCLUSION: Ligustrazine could inhibit platelet to release TXA₂, regulate the balance of TXA₂/PGI₂, restrain no reflow phenomenon, so it could prevent renal ischemia reperfusion injury.

Protective effects of diammonium glycyrrhizinate phospholipid complex on chronic liver injury

RU Ren-ping, CHEN Xiao-jin, YOU Lin-ya, TANG Hong-ying, CAI Han-ping, KUANG Rong

2009, 14(6):  642-645. 

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AIM: To approach the protective effects of diammonium glycyrrhizinate phospholipid complex injection (DG-PC)on chronic and immunological liver injury. METHODS: The chronic and immunological hepatic liver injury was established in C57BL/6J mice, the levels of ALT, AST, TP,ALB and HA in serum were determined, the contents of SOD,GSH and collagen 1 (C.I)in liver homogenate were detected, and the liver tissue sections were observed by electron microscope. RESULTS: Compared with DG, DG-PC could significantly improve the AST level, increase the content of ALB, increase the A/G, decrease the content of HA(P<0.01), improve the activities of SOD and GSH(P<0.01).The therapeutic efficacy of DG-PC was better than that of DG.As to microstructure, DGPC could protect the hepatic cell and organelle, and relieve the fibrosis level. CONCLUSION: DG-PC has protective effects on chronic and immunological liver damage to C57 BL/6J mice, which maybe relate to the antioxidant effects.

Research on ATR-FTIR finger prints of volatile oil in herbal pair Chuanxiong Rhizome-Paeonia Albiflora Pall and its single herb

ZHENG Chun-song, YE Hong-zhi, LIU Xian-xiang, LIN Zhi-feng

2009, 14(6):  646-649. 

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AIM: To study the chemical characteristics of volatile oil finger print of herbal pair Chuanxiong Rhizome-Paeonia Albiflora Pall(HP CXR-PAP). METHODS: Based on attenuated total reflectance-Fourier transform infrared (ATR-FTIR)spectroscopy, the FTIR spectrum of volatile oil in Chuanxiong Rhizome, Paeonia Albiflora Pall, and HP CXR-PAP were established, respectively.The spectra graphics of volatile oil inHP CXR-PAP were evaluated by the peak position, the peak shape and the peak intensity compared with the graphics of its single herb. RESULTS: The spectra of HP CXR-PAP was similar to that of its single herb, while the absorbance values of some kinds of chemical constituents were minished after compatibility. CONCLUSION: This is a direct, quick and accurate method to obtain the sample FTIR graphics, which reveals directly the chemical characteristics of HP CXR-PAP.

A Meta analysis on the effectiveness and safety of Mailuoning injection on cerebral infarction system

SHI Qing-ping, DING Feng, ZHU Jin-xiu, CHENG Peng, XU Shan-chu, LIU Yan

2009, 14(6):  650-654. 

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AIM: To evaluate the effectiveness and safety of Mailuoning injection on cerebral infarction system. METHODS: A systematic review of randomized controlled trials (RCT)of Mailuoning injection on cerebral infarction system was performed.Trials were identified by searching the Cochrane Library (issue 12, 2008),MEDL I NE (1966-2008), BMBASE (1984-2008) and CNKI (1979-2008).Two authors assessed the quality and reviewed the data independently.Statistical analysis was performed by using Rev Man 5.0.17.0. RESULTS: Thirteen trials ranked high quality were included.Meta-analysis of the treatment of Mailuoning injection on cerebral infarction system showed there were no significant differences between Mailuoning injection and the control group [OR 0.72, 95%CI 0.47 to 1.11), P=0.23].No serious systematical adverse reaction was recorded in the two trails. CONCLUSION: Mailuoning injection is an more effective and safe regimen for the treatment of cerebral infarction system than control group probably, but not certain.

Approach on Ch'an su dosage-effect relationship based on the human equivalent dose

MA Hong-yue, DUAN Jing-ao, ZHOU Jing, TANG Yu-ping, PAN Su-hua, DING An-wei

2009, 14(6):  655-658. 

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AIM: To approach the clinical dosageeffect relationship of Ch'an su. METHODS: The paper was performed by quoting/Literature data with animal effective doses to converse Ch'an su human equivalent dose (HED) range according to body surface area law. RESULTS: Ch'an su anti-inflammationHED was 9.8-39.2 mg/d, Ch'an su anti-tumor HED was 53.7-104.7 mg/d, the adverse reaction HED was 162-585.4 mg/d. CONCLUSION: Ch'an su anti-inflammation HED was smaller than the recommended dosage (15-30 mg/d), which suggested the clinical dosage is scientific and reasonable.But the anti-tumor HED was high, the upper limit and the HED dosege of secnetio bufonis poisoning were close, which suggested the dosage of Ch'an su for the clinical treatment of tumor should be designed cautiously.

Pharmacokinetic study on different compatibilities of Dangguibuxue Tang

WANG Wen-ping, CAO Qi-chen, WANG Hua-wei, LV Yu-ping

2009, 14(6):  659-663. 

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AIM: To explore the changed regularity of the pharmacokinetic parameters in animal plasma of astragaloside Ⅳ and ferulic acid when Astragalus and Angelica were used solely or compatibly in Dangguibuxue Tang, and to study the rationality of herbaceous compatibility of Dangguibuxue Tang. METHODS: The New Zealand white rabbits or SD rats were administrated with Astragalus, Angelica or Dangguibuxue Tang, respectively.The blood concentrations of ferulic acid in rabbits administrated with Dangguibuxue Tang or Angelica were analysised by HPLC, while the blood concentration of astragaloside Ⅳ in rats administrated with Dangguibuxue Tang or Astragalus were analysised by HPLC/MS/MS and the main pharmacokinetics parameters were calculated. RESULTS: Compared with single administration of Angelica, the pharmacokinetic parameters of ferulic acid in rabbit plasma almost did not show any change when administrated with Dangguibuxue Tang.Compared with administration with Astragalus alone, the t_max of Astragaloside Ⅳ in rat plasma was decreased significantly[from (4.00±1.54)h to (2.00±0.95)h] when given Dangguibuxue Tang, and its peak concentration was increased doublely [C_max from (60±7)μg/L to (146±27)μg/L)]. CONCLUSION: Angelica increases the vitality of Astragaloside Ⅳ in Astragalus in the body after the combination, and it advances the process of effectiveness of astragaloside Ⅳ, which embodies the adjuvant contribution of ministerial drug of Angelica. The experiment proves the rationality of Dangguibuxue Tang in terms of pharmacokinetics.

Effects of vitamin D receptor Fok I polymorphism on the transcriptional control of CYP3A4

WANG Guo, XIE Hai-tang, LI Bao-qun, FAN Lan, QIAN Rong-hua, HU Dong-li, LI Zhi

2009, 14(6):  664-669. 

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AIM: To study whether there is significant difference in the inductive effects on CYP3A4 between human vitamin D Receptor (hVDR) wild type and start codon Fok I mutant. METHODS: Total RNA was extracted from liver samples.cDNA of hVDR wild type was acquired by RT-PCR, and cDNA with hVDR Fok I mutant was acquired using site-directed mutagenesis.Eukaryotic expression vectors of both wild type and mutant of hVDR were constructed according to cDNA.Meanwhile, luciferase reporter gene vector was constructed with proximal ER6 element of CYP3A4. COS-7 cells with hVDR eukaryotic expression vectors, CYP3A4 luciferase reporter gene vector and the internal control vector were transiently transfected for 24 h and then were incubated with 1 nmol/L, 10 nmol/L and 100 nmol/L 1, 25(OH)₂D₃ for 48 h.Finally the cells were lysed and the luciferase activity was detected with cell lysis. RESULTS: hVDR eukaryotic expression vectors of wild type and Fok I mutant, and CYP3A4 luciferase reporter gene vector were successfully constructed.The results of luciferase activity showed that CYP3A4 transcription could be activated by hVDR eukaryotic expression vectors of wild type and Fok I mutant when incubated with 1 nmol/L, 10 nmol/L and 100 nmol/L 1, 25 (OH)₂D₃, respectively.However, there was no significant difference between the luciferease activities of hVDR wild type and mutant. CONCLUSION: Both hVDR wild type and Fok I mutant have inductive effect on CYP3A4 when incubated with vitamin D₃ (VD₃).But Fok I mutant could not significantly change the regulational capacity of wild type VDR on CYP3A4.

Effects of MDR1 gene C3435T polymorphism on the steady-state plasma concentration and hypotensive activity of telmisartan

FAN Xiu-zhen, GUO Xin, WANG Hua-jie, CHENG Ze-neng

2009, 14(6):  670-676. 

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AIM: To study the effects of MDR1 C3435T polymorphism on steady-state plasma concentration and hypotensive activity of telmisartan. METHODS: 61 cases of essential hypertension patients were received oral dose of 40 mg telmisartan per day for 30 days.The genotyping of the MDR1 C3435T polymorphism in the patients was performed by using method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The plasma concentrations of telmisartan were determined by high performance liquid chromatograpy-Fluorescence detector (HPLC-FLD).The blood pressures of the patients were measured before and after treatment.The plasma concentrations and therapeutic effect of telmisartan were compared among the three different genotype groups. RESULTS: Among the 61 cases of elderly hypertension patients, the frequencies of 3435CC, 3435TT and 3435CT were 39.34%, 11.48% and 49.18%, respectively.There were no differences between healthy people and the hypertension patients in allele frequencies of MDR1 C3435T.The telmisartan steady-state concentration and curative effect also had no significant differences among the three genotype groups in the hypertensive patients. CONCLUSION: The MDR1 C3435T polymorphism does not affect the steady-state plasma concentrate and curative effect of telmisartan in hypertension patients.

Research on pharmacokinetics of ropivacaine methanesulfonate in patients

WANG Shao-hua, ZHAO Yan, LIU Zhen-sheng, YAN Mei-xing, LI Zhi-ping, AI Deng-bin, SUN Li-xin

2009, 14(6):  677-680. 

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AIM: To study the pharmacokinetic profiles of ropivacaine methanesulfonate in patients and research the sex differences between these parameters. METHODS: 15 mL ropivacaine methanesulfonate injection was given when the patient had an epidural anesthesia.The concentrations of ropivacaine in plasma were determined by HPLC.The parameters of pharmacokinetics were calculated by DAS software. RESULTS: The pharmacokinetic parameters of male and female after administration with ropivacaine methanesulfonate injection were as follows:the t_1/2β were (4.050±2.548) and (2.088±0.135)h;the t_1/2Ka were (0.085±0.045) and (0.107±0.069)h;the t_max were (0.333±0.118) and (0.417±0.167)h; the C_max were (1.066±0.135) and (1.113±0.317) mg/L;the AUC_0-tn were (2.856±0.321) and (2.369±0.386)mg·L^-1·h;the MRT0-tn were (2.070±0.113) and (2.022±0.089)h, respectively. CONCLUSION: The methodology to determine plasma concentration by HPLC and pharmacokinetic profiles of ropivacaine methanesulfonate injection were achieved. The results showed that there were no sex differences statistically between the pharmacokinetic parameters.

Therapeutic effects of the new compound codonopsis tablets against deacclimatization to high altitude

ZHANG Dong-xiang, NIE Hong-jing, ZHANG Yan-kun, ZHANG Ru-jun, CUI Jian-hua, CHENG Yue, ZHANG Yan-fang, CUI Wen-yu, XIAO Zhong-hai, WANG Yin-hu, YIN Zhaoyun, LIU Jia-ying, WANG Hai

2009, 14(6):  681-685. 

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AIM: To study the therapeutic effects of new compound codonopsis tablets against deacclimatization to high altitude. METHODS: Forty-three male soldiers stayed at 5200 m altitude for one year were randomly divided into two groups:control group (15 men) and treatment group (28 men).Single blind trial was used in this study.Five days before they return to plain (1400 m), they were taken placebo and new compound codonopsis tablets respectively until they arrived in for one week.The questionnaire of symptoms of deacclimatization to high altitude was used on the 2nd, 4th, 6th day after they returned to 1400 m altitude.On the 7th day after returning to 1400 m, FVC (forced vital capacity), FEV_1.0 (forced expired volume in one second), FEV1% (FEV_1.0 FVC), FEF25%-75%, PEF (peak expiratory flow) and MVV (maximal voluntary ventilation) were determined with a spirometer (SriroAnalyzer ST-75), total frequency of hands cross movement and memory of order numbers were tested with a neurosychological monitoring system (DDX-200). RESULTS: Compared with control, symptoms of deacclimatization to high altitude of treatment group were reduced significantly on the 2nd, 4th, and 6th day after returning to 1400 m (P<0.01).The degree of symptoms of deacclimatizating to high altitude in treatment group was distinctly different from that of control (P<0.01).The proportion of slight symptoms in treatment group was high, and that of relative serious symptoms was low.Compared with control, FVC, FEV_1.0, PEF and MVV of treatment group were increased significantly (P<0.05, P<0.01).Ttis, Ctis in treatment group were increased (P<0.05), Atime was decreased markedly (P<0.05).There was no statistically significant difference in Etis and Sum between the two groups. CONCLUSION: New compound codonopsis tablets could decrease the incidence of deacclimatization to high altitude, mitigate the symptoms of deacclimatization to high altitude, improve the breathing function and fingers movement function.New compound codonopsis tablets have a significant effect on prevention and treatment of deacclimatization to high altitude.

Effects of activated Vitamin D₃ treatment on microinflammation state in maintenance hemodialysis patients

WANG Bi-fei, ZHU Sheng-lang, YANG Jing-xing, XIE Chu-neng, LIU En-bo

2009, 14(6):  686-690. 

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AIM: To explore the effect of activated Vitamin D₃ treatment onmicroinflammation state in maintenance hemodialysis patients. METHODS: 33 maintenance hemodialysis patients with intact parathyroid hormone(iPTH) levels above 300 pg/mL were received activated Vitamin D₃ orally pulse therapy for 12 weeks. Serum iPTH, calcium, phosphorus and inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) were tested before and 4, 12 weeks after the treatment.Echocardiographic parameters of left ventricular hypertrophy were examined before and after the the treatment. RESULT: Both 4 weeks and 12 weeks after 1, 25(OH)₂D₃ treatment, serum IL-6 and CRP levels were reduced significantly.4 weeks after the treatment, serum iPTH levels had no significant change.12 weeks after the treatment, serum iPTH levels were decreased remarkably compared to that before 1, 25 (OH)₂D₃ treatment.Compared with before treatment, the iPTH level was decreased after 12 weeks treatment, 48.5% of the patients reached end-point parameter (iPTH<300 pg/mL).Left ventricular hypertrophy parameters determined by echocardiography were significantly improved after 12 weeks treatment. CONCLUSION: Activated vitamin D₃ can attenuate the microinflammation state in maintenance hemodialysis patients and improve left ventricular hypertrophy.These data suggest that activated vitamin D₃ may have broad application other than modulating calcium, phosphorus metabolism and controlling iPTH in maintenance hemodialysis patients.

Analysis of bacteria and their drug resistance in intensive care unit

WANG Yu-ping, LI Xiao-ning, WANG Ming-hua, LIU Chun-sheng

2009, 14(6):  691-694. 

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AIM: To study the distribution of infectived bactarial In ICU and analyze their drug resistant rates. METHODS: 228 specimens were cultivated, the identification of bacteria and drug susceptibility were tested in the positive specimens. RESULTS: 186 specimens including bacteria were detected from 228 (accounted for 81.6%), which 42 specimens including gram positive coccus(accounted for 18.4%), and 144 specimens including gram negative bacilli(accounted for 63.2%), the staphylococcus aereus was primary in gram positive coccus, the first three bacilli were acinetobacter, pseudomonas aeruginosa, klebsiella pneumonice in gram negative bacilli, the resistant rates of the gram positive bacterium to other drugs were more than 80% except perfectly susceptibility to vancomycin, the decreasing susceptibility order among gram negative bacilli was cefoperazone sulbactam, piperacillin tazobactam, Meropenem.The resistant rate of pseudomonas aeruginosa to ceftazidime was 31%, the resistant rates to other drugs were more than 60%. CONCLUSION: There is higher infected rate, more kinds of infected bactiria and more serious resistant rates to ICU patients, it is necessary to choose antibiotic reasonably according to the results of drug susceptibil.

Research progress on traditional Chinese medicine affecting the metabolism of cytochrome P450

XIE Rui-fang, ZHOU Xin

2009, 14(6):  697-700. 

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Cytochrome P450 is one of the microsomal mixed function oxidase, and plays an important role in the metabolism of exogenous and endogenous material.Lots of domestic and overseas relative literatures were red, the article summarized the research progress of traditional Chinese medicine affecting the metabolism of CYP in recent years.Eight main drugmetabolizing enzymes were respectively introduced, including CYP1A1, CYP1A2, CYP2A6, CYP2C, CYP2D6, CYP2E1, CYP3A4 and CYP3A4.It is important to research CYP450 for drug screening, individual administration.

Advancement on pharmacogenomics of partial antitumor drugs

HUA Zhi-hui,HOU Ying, SONG Hong-tao

2009, 14(6):  701-706. 

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Recently, diverse effects and side effects of antitumor drugs induced by individual difference have received considerable attention.Studies on pharmacogenomics show that genomic polymorphism is closely associated with individual difference and side effects of antitumor drugs.The paper summarizes the advancement on pharmacogenomics of partial antitumor drugs.

Advancement on the therapy of somatostatin on liver fibrosis

XU Xiao-bing, YANG Miao-fang, ZHU Ren-min

2009, 14(6):  707-710. 

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Somatostatin, a cyclopeptide hormone, is generally distributed in vivo.Some studies have indicated that somatostatin can reduce proinflammatory cytokine in hepatic stellate cells and extracellular matrix, and inhibit their proliferation and contraction, promote their apoptosis.It can also regulate the function of Kupffer cells, influence the homing of hepatic stem cells.Somatostain has therapeutic effect on liver fibrosis, especially on the liver fibrosis caused by schistosoma mansoni.

Regulation of β amyloid protein level in the brain

WANG Ying-yu, WU Jing, HONG Hao, JI Hui, WU Yu-lin

2009, 14(6):  711-714. 

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β amyloid protein (Aβ) including Aβ₄₀ and Aβ₄₂ are the important bioactive substances in vivo.Their toxic and beneficial attributes in the body depend on its concentration.The brain Aβ level is maintained by two balances under the physiological condition.The first balance is the generation involved in β-secretase and γ-secretase and the degradation involved in neprilysin (NEP) and insulin-degrading enzyme (IDE) of Aβ.The second one is the balance between the receptor for advanced end glycation products (RAGE)-mediated influx and low-density lipoprotein receptor related protein 1 (LRP1)-mediated eff lux of Aβ across the blood-brain barrier (BBB).Breakdowning any one of the two balances would result in the aggregation and precipitation of Aβ in the brain, which is a crucial event in the pathogenesis of Alzheimer's disease (AD).This paper reviews the regulation of brain Aβ level under the physiological condition and the reducing strategies on the level of brain Aβ under the pathological condition for developing new drugs in the treatment of AD.

Quantitation of drug concentration in hair and its application in drug monitoring

ZHANG Yu-shan, SONG Jian-guo

2009, 14(6):  715-720. 

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Hair can be easily collected, the collection method does not cause any harm to body.It can provide long and convinced information about drug uses.It possess irreplaceable advantages of blood, urine and other biological samples.The review summarizes the basic information and recent studies of hair analysis.It introducs the hair-shaft structure, the mechanisms of drug incorporation, extraction/purification methods and all kinds of analytical techniques.The advantages, drawbacks and promising prospects about hair in drug monitoring are also discussed.