Table of Content

Volume 12 Issue 3
26 March 2007

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Development of clinical nano-particles and oral gene medicine

XU Rui-an

2007, 12(3):  241-249. 

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Oral medicine is one of the main methods for disease prevention and treatment.It is very popular in healthcare due to its convenience, efficiency, comfort and safety.However, there is still a lack of qualitative and quantitative information how about macro-molecules, and nano-particles in particular, are taken up and absorbed in the gastrointestinal tract.This paper systematically describes relationships between features of nano-particles, protein transduction, and uptake cell types at gastrointestinal sites and the uptake and absorbance of nano-particles.Development of the route for orally-delivered gene medicine, and particularly the uptake, distribution, pharmakinetics, feasibility and system evaluation of orally viral vectors is explored.Trends in and obstacles to the delivery, expression, production and release of oral gene medicine are also discussed.

Interactions of intestinal H⁺ oligopeptide cotransporter PEPT1 with drugs and regulation by affecting factors

ZHANG Qing-hao, LIU Ke-xin

2007, 12(3):  250-257. 

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H⁺ oligopeptide cotransporter PEPT1 mainly located at the brush border membrane of intestinal epithelium cell.transports dipeptide tripeptide which is the degradation products of protein in digestive tract. Peptide-like drugs such as β-lactam antibiotics, angiotensin-converting enzyme inhibitor (ACEI)and non-peptide drugs valaciclovir also can be transported and uptaked by PEPT1.PEPT1 is important for maintaining the homeostasis and the absorption of drugs in gastrointestinal tract.With the further research of PEPT1 gene, protein structure, and functional activity, we have known the factors about regulation of PEPT1 expression in membrane, their functional activities and substrate affinities.Some associated mechanism of regulation have been studied.As the wide substrate specificities of PEPT1, it becomes the target molecular on drug development and implication for drug delivery.Studies about interactions of PEPT1 with drugs are important for knowing the interactions of drugs, evaluating bioavailability of drug by intestinal absorption, researching the target treatment in anti-tumor drugs and individualization administration.

Review of new cholesterol absorption inhibitor ezetimibe

ZHANG Xin-bo, WANG Lv-ya

2007, 12(3):  258-261. 

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Ezetimibe, a new selective cholesterol absorption inhibitor, may decrease the absorption of cholesterol and plant sterol by inhibiting the cholesterol absorption protein Niemann-Pick C1 like 1 (NPC1L1) in the enterocytes.Ezetimibe apparently reduces the plasma low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) level, which provides a new approach for the therapy of hypercholesterolaemia, artherosclerosis and coronary artery disease.

Relationship between type 2 diabetes and leptin resistance and its gene polymorphisms

LIU Hai-ling, TAN Yuan-ming, LIU Zhao-qian

2007, 12(3):  262-265. 

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Leptin has many important pathophysiological effects, such as inhibiting insulin secretion and expression, constraining pancreatic β cell apoptosis and controlling glucose metabolism through skeletal muscle cell and hepatic cell.This review summarizes the phenomena of leptin resistance and leptin gene polymorphism in vivo, particularly emphasizing its correlation with type 2 diabetes and drugs clinical effective.

Advances in study of estrogen and its receptors signal transduction pathway

FAN Guan-wei, HE Jun, WANG Hong, GAO Xiu-mei

2007, 12(3):  266-269. 

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Estrogen gradually becomes the research hot spot because it has extensive biological effect, which exerts its function by binding to estrogen receptors (ERs).ERs have the widespread organization distribution, including the reproductive system, the skeleton and the cardiovascular system, and these provided the guarantee for the estrogen to display biology effect.This article reviews the advance of estrogen and its receptors signal transduction pathway in abroad and domestic.

Dual activities of PAF in central nervous system and its values in development of new drugs

LI Juan, CHEN Hong-zhuan

2007, 12(3):  270-274. 

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Platelet-activating factor (PAF), an endogenous bioactive lipid generated by phospholipase A2 and other pathways, displays a variety of biological activities in the nervous system.It has been suggested that PAF plays important roles in neuronal physiological functions including acting as a retrograde messenger to enhance synapse plasticity and memory formation, via activation of its specific membrane receptors.Therefore, the drugs that mimic the action of PAF or modulate the production and inactivation of PAF maybe promising in memory-enhancing.However, under certain pathological conditions, such as Alzheimer' s disease, HIV-associated dementia or post-ischemic neuronal death, acting as a potent inflammatory mediator and neurotoxin, PAF has been implicated in the pathophysiology of brain injury.So, modulating the metabolism and effects of PAF (e.g., blocking the PAF receptor) may become important strategies of intervention of Alzheimer' s disease, HIV-associated dementia or postischemic neuronal death.

Transfer of interleukin 6 gene into MCF-7 human breast cancer cells enhances expression of tumor-associated antigens

JIANG Xian-peng, Robert L.Elliott, Jonathan F.Head

2007, 12(3):  275-281. 

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AIM: To investigate the mechanism by which IL-6 is involved in cancer prognosis, and further to demonstrate the relationship between IL-6 and tumor-associated antigens such as CA15-3, CEA and CA125 in breast cancer.METHODS: In the present study, we transfected an exogenous IL-6 gene into the MCF-7 cells. Secretion of CA15-3, CEA and CA125 into the culture media were measured by Enzyme Linked Immunosorbent Assay (ELISA).RESULTS: After a 72 hours in culture, the amount of IL-6 in the media of pCI-neo-IL-6-transfected MCF-7 cells (338.5 ±22.6 pg/10⁶ cells) was significantly higher than that of non-transfected MCF-7 cells (25.4 ±4.6 pg/10⁶ cells, P <0.01, paired ttest), or pCI-neo-transfected MCF-7 cells (19.6 ± 3.0 pg/10⁶ cells, P <0.01, paired t-test).The levels of CA15-3, CEA and CA125 secreted by the pCI-neo-IL-6-transfected MCF-7 cells were significantly higher than that of the parental MCF-7 cells or pCI-neo-transfected MCF-7 cells.The specific IL-6 antibody could decrease the expression of CA15-3, CEA and CA125 in both the MCF-7 cells and the IL-6 cDNA-transfected MCF-7 cells. CONCLUSION: Transfer of IL-6 gene augments tumorassociated antigens of human breast cancer cells.The association of elevated IL-6 concentration with a poor prognosis in cancer patients may partially be the result of increased expression of tumor-associated antigens by IL-6.

Effect of propofol on cytotoxicity and endogenous thioredoxin system induced by bupivacaine in pheochromocytoma PC12 cells

WANG Qiang, XU Li-xian, ZHANG Hui, ZHU Xiao-ling, XIONG Li-ze

2007, 12(3):  282-286. 

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AIM: To investigate protective effect of propofol on the cytotoxicity of bupivacaine in pheochromocytoma PC12 cells of rat and role of endogenous thioredoxin (Trx) system.METHODS: The PC12 cells were inoculated and cultured on the culture capsule.The cultured PC12 cells were randomly assigned to one of four groups (n =6 holes each):Control group, bupivacaine group (B), propofol group (P) and bupivacaine combined with propofol group (BP).Survival rate of PC12 cells (%) treated with different drugs for 6 and 24 h induced was analyzed by MTT assay.Lactate dehydrogenase (LDH) in the culture medium was measured by spectroscopy.Thioredoxin reductase (TrxR) and ROS activities in the PC12 cells were assayed by spectrophotometer.The expression levels of Trx mRNA and TrxR mRNA were determined by RT-PCR.RESULTS: Compared with normal PC12 cells, bupivacaine significantly reduced the relative survival rate (P <0.01) and TrxR activity of the PC12 cells (P <0.05), markedly increased level of LDH in the culture medium(P <0.05) and ROS activity in the PC12 cells (P <0.01), and significantly decreased the expression of Trx mRNA and TrxR mRNA (P <0.05). Compared with B group, the relative survival rate of the PC12 cells were significantly increased (P <0.01) and TrxR activity of the PC12 cells were increased (P < 0.05);The level of LDH in the culture medium(P < 0.05) and ROS activity in the PC12 cells markedly decreased (P <0.01);The expression of Trx mRNA and TrxR mRNA was significantly increased (P <0.05) in PB group compared with those in B group.CONCLUSION: Bupivacaine induces cytotoxicity in the PC12 cell line, which may be associated with ROS production and decrease in TrxR activity.Propofol can prevent cytotoxicity of PC12 cells induced by bupivacaine, and one of the mechanisms may be associated with protecting endogenous thioredoxin system and scavenging ROS production.

Determination of N^G-nitro-arginine enantiomers in biological samples with chiral ligand exchange method by capillary electrochromatography

XIN Yan-fei, LI Li-li, MA Ai-niu, WU Mei, ZHOU Xiang-jun, WANG Yong-xiang

2007, 12(3):  287-290. 

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AIM: To study the chiral separation of NG-nitro-arginine enantiomers in biological samples by capillary electrochromatography (CEC).METHODS: The separation of D-NNA and L-NNA in plasma was achieved by chiral ligand exchange method via CEC.An aqueous eluent containing aspartame (2 mmol/L) sufficiently mixed with Cu²⁺ was used.The eluent was monitored at UV 280 nm.RESULTS: The retention times were 16 and 19 min for L-NNA and D-NNA, respectively.The standard curves of D-NNA and L-NNA ranged from 0.025 to 0.75 mmol/L (R² >0.98).The withinday precision of the quality control samples was 3.0 %for both L-NNA and D-NNA.The between-day precision was 3.1 % for L-NNA and 3.4 % for D-NNA, respectively.CONCLUSION: This method was established to determinate D L-NNA in biological samples with high resolution and efficiency.

Development of tissue cage infection model and study of efficacy of levofloxacin in treatment of staphylococcus aureus infection

CUI Jun-chang, LIU You-ning, WANG Rui, TONG Wei-hang, LI Zhao-xia

2007, 12(3):  291-294. 

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AIM: To develop tissue cage infection model and study the efficacy of levofloxacin in treatment of staphylococcus aureus infection.METHODS: A plastic ball was implanted into each rabbit through a dorsal midline incision under aseptic conditions.By 4 weeks after implantation, each plastic ball had filled with clear, yellowish tissue fluid.To develop tissue cage infection model, staphylococcus aureus culture was injected into each preimplanted plastic ball.Rabbits were administered levofloxacin at different dose once daily by use of a gavage feeding tube.Tissue cage fluid was taken out from the plastic ball, and concentration of bacteria and loss of susceptibility were monitored in tissue cage fluid.RESULTS: Levofloxacin at 5 mg/kg caused bacterial numbers to decrease throughout treatment.Doses of levofloxacin at 10 or 20 mg/kg reduced bacterial numbers for the first 3 days, but bacterial growth was observed during late stage of treatment and during post-treatment observation. Levofloxacin at 40 mg/kg caused bacterial numbers to decrease throughout treatment and to remain low level during the growth recovery period.Dose of levofloxacin at 5 or 10 or 20 mg/kg caused the loss of susceptibility easily, but no resistance occurred at dose of 40 mg/kg.CONCLUSION: The bacterial response and occurrence of resistance depend on the levofloxacin dose.

Changes of myocardial membrane gene expression of natrium pump isoforms in rat with myocardial ischemia reperfusion injury

KE Yong-sheng, CHU Yue-feng, YU Guo-hua, YANG Hao

2007, 12(3):  295-298. 

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AIM: Changes of endoxin level, ATPase activities, intramitochondrial Ca²⁺ concentration, and gene expression of Na⁺-K⁺-ATPase isoforms in myocardium of rats with MIR and effect of verapamil were observed, in order to investigate mechanism of endoxinmediating intracellular calcium overload of myocytes.METHODS: Twenty four male Sprauge Dawley rats were randomized into 3 groups.Sham operation group:silk suture was threaded the left anterior descending coronary artery without ligature;MIR group (MIR):left anterior descending coronary artery was subjected to 30 min ligation followed by 45 min reperfusion;verapamil group:MIR model was given 5 mg/kg verapamil.Verapamil was injected via femoral vein 5 min before reperfusion.Left ventricle myocardium samples were processed immediately after reperfusion in order to measure the activities of Na⁺-K⁺-ATPase and Ca²⁺-²⁺-ATPase, endoxin level, and intramitochondrial Ca²⁺ concentration.The levels of α₁, α₂, α₃ and β₁ isoforms of Na⁺-K⁺-ATPase were measured by immunohistochemical assay.RESULTS: After MIR, the level of endoxin in myocardium was substantially increased; the activities of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase in myocardial membrane were significantly decreased while the concentration of intramitochondrial Ca²⁺ was increased;the levels of the α₁, α₂, α₃ and β₁ isoforms of Na⁺-K⁺-ATPase were reduced markedly. Verapamil had only effect on reducing the concentration of intramitochondrial Ca²⁺.CONCLUSION: MIR increases endoxin secretion.The latter may depress the activity of Na⁺-K⁺-ATPase by changing the gene expression of α₁, α₂, α₃ and β₁ isoforms of Na⁺-K⁺-ATPase in myocardial membrane, inducing intramitochondrial Ca²⁺ overload.

Investigation of rat osteoporosis resulting from hyperlipidemia

YOU Ting-ting, WU Tie, ZHANG Zhi-ping, ZOU Li-yi, HUANG Bo

2007, 12(3):  299-303. 

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AIM: To establish the hyperlipemic rat model by long-term gastric perfusion of intralipid and investigate the effects of hyperlipidemia on bone.METHODS: Eighteen SD rats were randomly divided into control group (C) and high-fat-diet group (HDF), with 9 rats per group.Rats of C group were treated orally with normal saline, and rats in HDF group were oral gavage of intralipid at dose of 5.0 mL/kg, once a day for 20 weeks. At the end of experiment, their serum levels of lipid were measured.Bone histomorphometric analysis of thighbone was performed in undecalcified sections, and the length and width of ulnar were measured.RESULTS: Compared with the C group, serum TC and low density lipoproteins (LDL) were increased (P <0.01) and high density lipoproteins (HDL) were decreased (P <0.01). Bonehistomorphometric parameters showed a significant bone loss in the model group (P <0.01).CONCLUSION: Bone loss occurs in the hyperlipemic rat model by long term gastric perfusion of intralipid.

Inhibition of Okam extract J201 on bleomycin induced pulmonary fibrosis in rats

ZHANG Zheng-shou, JIANG Han-dong, WANG Li-na

2007, 12(3):  304-307. 

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AIM: To investigate the protective effect of Okam extract J201 on bleomycin induced pulmonary fibrosis in rats and the underlying mechanism.METHODS: Forty-six Wistar rats were randomly divided into four groups.Pulmonary fibrosis was induced by intratracheal instillation of bleomycin.The histopathological changes of the lungs, lung weight index, contents of malondialdehyde (MDA) and hydroxyproline (HYP) in lung homogenate were investigated, and the immunohistochemical techniques were used to investigate the expressions of factor associated suicide (Fas), Fas ligand (FasL), matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-2(TIMP-2) with a view to evaluating the effects of J201.RESULTS: Dose-dependent improvement in lung histopathology induced by bleomycin was noted in J201-treated group.Lung weight index and the contents of MDA and HYP were reduced by addition of J201.There were also decreased expressions of Fas, FasL, MMP-9 and TIMP-2 by J201.Dose-dependent relationship was observed, and the expressions of Fas, FasL, MMP-9 and TIMP-2 of pulmonary fibrosis induced by bleomycin were inhibited in rats.The effect of J201 on lung index, MDA, HYP, Fas, FasL, MMP-9 and TIMP-2 was in a dose-dependent manner.CONCLUSION: J201 shows protective effects on the pulmonary fibrosis induced by bleomycin in rats.Antioxidation and inhibition of the expression of Fas, FasL, MMP-9 and TIMP-2 in lung tissues may be one of the underlying mechanisms.

Effects of Guixin granule on nitroglycerin-induced migraine in rats

LIU Lin-na, CHENG Jian-feng, ZHANG Yan, GUO Shu-yun, LIU Xin-you, RU Guan-lan

2007, 12(3):  308-312. 

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AIM: To investigate the effects of Guixin granule (GXG) on behavior and symptoms of nitroglycerin-induced experimental migraine model and its possible mechanism in rats.METHODS: SD rats were used in the experiment.Flunarizine(Xibiling capsule, XBLC) was used as positive control.Guixin granule and Xibiling capsule were given to the rats through intragastric route.At 7 d after administration, nitroglycerin was injected subcutaneouly (9 mg/kg) to induce migraine model.Changes of behavior and symptoms were continuously observed at various intervals.The content of 5-hydroxytryptamine (5-HT) in the rats' blood and brain tissue was detected by fluorescence spectrophotometry.RESULTS: Compared with the model group, the symptom of GXG groups was improved significantly.And GXG could obviously increase the concentration of 5-HT in the blood and the brain (P <0.05 or P <0.01).CONCLUSION: The possible mechanism of GXG on improving the behavior and symptoms of migraine in rats may be through the increase in the content of 5-HT in blood and brain.

Effects of sevoflurane inhalation on ultrastructure changes in lung tissue during ischemia-reperfusion lung injury in rabbits

HU Ming-pin, CHEN Ling-yang, LI Xing-wang, LIAN Qing-quan, FANG Zhou-xi

2007, 12(3):  313-316. 

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AIM: To investigate the effects of sevoflurane inhalation on the ultrastructure changes in lung tissue during ischemia-reperfusion lung injury in rabbits and explore the underlying mechanisms.METHODS: Seventy two Japanese long-ear white rabbits weighing 2.5-3.0 kg were randomly divided into four groups (n =18):sham operation group S;IR group in which hilum of left lung was clamped for 45 min and then unclamped for reperfusion for 120 min;Sev-IR group in which 1MAC sevoflurane was inhaled for 30 min before ischemia;Sev-S group 1MAC in which sevoflurane was inhaled for 30 min without IR.The ultrastructure changes in lung tissue were observed under electron microscopic at 45 min after pulmonary ischemia, 60 and 120 min of reperfusion.Myeloperoxidase of lung was measured at 120 min of reperfusion.RESULTS: In group IR:pneumonocyte Ⅰ and vascular endothial cell became swollen and deteriorated;there were reduced microvilli on the surface of pneumonocyte Ⅱ, and Ⅱ type alveolar epithelial cells were swollen or vesicular and plenty of polymorphonuclear neutrophils stayed in capillary chambers.The increased levels of myeloperoxidase in group IR and group Sev-IR were significantly higher than those in group S, but compared with group IR, group Sev-IR could inhibit the increase of myeloperoxidase after 120min of reperfusion (P <0.05).CONCLUSION: Sevoflurane attenuates the IR-induced pulmonary ultrastructural changes, possibly through an inhibition of polymorphonuclear neutrophil recruitment into the lung.

Effects of propafenone on interventricular repolarization heterogeneity in ischemic myocardium in rabbits

GE Li-hua, LI Yun-tian, LI Cui-lan

2007, 12(3):  317-320. 

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AIM: To observe the effects of propafenone on interventricular repolarization heterogeneity between two ventricles in isolated ischemic myocardium in rabbits, and with the action potential duration (APD), to approach the electropharmacologic mechanism of arrhythmogenic of propafenone in patients with myocardium ischemia in clinical practice.METHODS: To observe the effect of propafenone, we gave various concentration gradient (1, 6, 10 μmol/L) on the APD of endocardium myocytes in ischemic state with whole cell patch-clamp through alterring frequency of stimulation.RESULTS: Propafenone could enlarge the interventricular repolarization dispersion when the concentration of propafenone from 1 to 10 μmol/L.The endocardium APD characterized dependence on slow frequency when given various gradients of propafenone (P <0.05) and this characteristic was independent on the gradients of propafenone.But the slowfrequency dependence of interventricular dispersion was not observed in same condition. CONCLUSION: Propafenone can significantly increase the interventricular repolarization heterogeneity in ischemic myocardium and make the slow-frequency dependence of interventricular dispersion disappear.It may be one of the electropharmacological mechanism of arrhythmogenic of propafenone in ischemic myocardium.

Isolation purification and identification of soluble peptidoglycan from staphylococcus aureus

ZHANG Xiang-wu, ZHENG Jiang, FU Jian-feng, GUO Yi-bin, CHEN Yi-guo, LU Yong-ling

2007, 12(3):  321-323. 

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AIM: To extract and identify the soluble peptidoglycan from staphylococcus aureus.METHODS: The soluble peptidoglycan from staphylococcus aureus (ATCC25923) was released by short dose penicillin. Then, the soluble peptidoglycan was purified by sephadex G-100.The SLP reagent set was employed to identify the purified soluble peptidoglycan, and the production stimulated by the purified soluble peptidoglycan in RAW264.7 cell was observed by ELISA.RESULTS: Detected by the SLP reagent, the purified soluble peptidoglycan showed positive.The purified soluble peptidoglycan was capable of stimulating the production of TNF-αin RAW264.7 cell, and the amounts of TNF-αreleased were directly proportional to the concentrations of PGN.CONCLUSION: The soluble peptidoglycan from staphylococcus aureus can be obtained by penicillin and sephadex G-100, which has higher biological reactivities.

Study on antitumor mechanism of Qingre Xiaozheng drink by molecular docking method

CHEN Li-wu, ZHENG Chun-song, DU Jian

2007, 12(3):  324-328. 

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AIM: To study the effect of Qingre Xiaozheng drink (QRXZD)on tumor growth and its mechanism.METHODS: Molecular docking serves as a method to simulate the interactions of Chinese medicine small molecules and TNF-α, Bcl-xl and CDK2 receptors by ligand-fit module of the software package Cerius2 4.10 made by Accelrys company, and we may predict QRXZD on anti-tumor mechanism.RESULTS: Fifteen molecules were shown to be better interactions with Bcl-xl than an original ligand, and thirty molecules were observed to be better interactions with TNF-αthan an original ligand. The number of molecule interacting with CDK2 was twenty three.Its mechanism could be direct toxicity for tumor cells to induce apoptosis;Simultaneously the mechanism might interfere the activity of CDK2 to stop tumor cell going ahead from G1 period to S period.CONCLUSION: Molecular docking method is simple, speedy and strong scientificness, which can be used to study the mechanism of the Chinese medicine.

Pharmacokinetic-pharmacodynamic modeling and simulation:concepts and basic principles(2)

HUANG Xiao-hui, SHI Jun, LI Jun, SONG Guo-qiang, XIE Hai-tang, ZHENG Qing-shan, SUN Ruiyuan

2007, 12(3):  334-341. 

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Modeling and simulation (M&S) is an important research field in pharmacokinetics and pharmacodynamics.M&S has evolved from a tool primarily applied to therapeutic drug monitoring to one that plays a significant role in drug development.Technological advances in various fields related to drug development call for more focus on ways to optimize current drug development practices.Recognition of the potential of M&S by regulatory agencies inevitably has a substantial impact on drug development.The objective of the current review is to present the some basic concepts and principles of M&S. Some case studies are presented to illustrate how M&S can facilitate knowledge management and decision making.In this article the model development process and goodness of fit criteria were discussed.

Determination of lomerizine hydrochloride in human plasma by HPLC-MS

HE Jian-ping, HUANG Hai-yan, CHAO Yang

2007, 12(3):  342-345. 

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AIM: To develop a HPLC-MS method for determining the concentration of lomerizine hydrochloride in human plasma.METHODS: Lomerizine was determined by LC-ESI-MS selection ion measurement.Separation was performed on a Lichrospher C₁₈ with a mobile phase of 0.01mol/L ammonium acetate (pH 3.5):methanol (22:78).RESULTS: Calibration curves were linear in the concentration range of 0.10-10.02 ng/mL (r =0.9993).The quantitative detection limit in plasma was 0.10 ng/mL.RSD of intra-batch and inter-batch assays were all less than 8.59 %.The relative recovery ranged from 100.2 %to 105.9 %and the absolute recovery ranged from 85.58 % to 92.03 %.A single oral dose 10 mg lomerizine hydrochloride capsule or tablet was given to 20 healthy volunteers according to an open randomized crossover study.The concentration of lomerizine hydrochloride in plasma was determined by HPLC-MS method, and the relative bioavailability of AUC_{0 ～ 24} was 103.4 % ±15.6 %.CONCLUSION: This method is rapid, simple, sensitive and accurate for the determination of lomerizine hydrochloride in human plasma.

Main points of design about phase I tolerant clinical trials of injectable preparation

HAN Rong, XUE Jie, QI Jian-guo

2007, 12(3):  346-348. 

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In order to consummate the various specification in phase I tolerant clinical trials, through using medicine dosage, increasing the dosage plan, the treatment course, choosing the fluid, giving the medicine method, stochastically entering the group, the physics and chemistry result judgment, human body responding aspect and so on, we summarize and propose the standard sequence of operation.It proves effective to improve the quality from the clinical trials.

Thinking on ethical principle in bioequivalence studies

QIAN Wei, YANG Jin, CHEN Lei, XIAO Da-wei

2007, 12(3):  349-351. 

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The clinical trails should be conducted in accordance with the ethical principles that have their origin in the declaration of Helsinki and that are consistent with GCP.A trial should be initiated and continued only if the anticipated benefits justify the risks.According to the principle, this paper gives some thinking on the ethical principle in bioequivalence study of some special drugs.

Role of intrahepatic HBV DNA in antivirus therapy

LU Hai-ying, ZHUANG Li-wei, YU Yan-yan, SI Chong-wen, LI Jun, CHEN Xin-yue, HAN Zhong-hou, CHEN Yong

2007, 12(3):  352-356. 

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AIM: To study the role of intrahepatic HBV DNA in antiviral therapy.METHODS: 71 patients with HBeAg-positive chronic hepatitis B were studied. Twelve patients were treated with INF-α2b;thirty-five patients received lamivudine;twenty-four patients were administered by sequential therapy with Lamivudine-INF-α2b (at first, lamivudine alone from first to 6th month, then lamivudine combined with INF-α2b from 7th to 8th month, finally INF-α2b alone from 9th to 12th month). Liver biopsy specimens were obtained before and after treatment.Blood samples were collected once a month during the period of treatment, in the thirdmonth, and in the sixth month after cessation of therapy.Serum and intrahepatic HBV DNA were measured quantitatively by real-time polymerase chain reaction.HBV genotypes were analyzed by PCR-RFLP.RESULTS: There was no significant difference in intrahepatic HBV DNA levels between the patients infected by HBV genotype C (60 cases) and genotype B (10 cases) (P >0.05).Intrahepatic HBV DNA logarithm levels in the patients with therapy response decreased from (5.9 ±1.0) to (4.5 ±1.2) (P <0.05).Patients with intrahepatic HBV DNA logarithm level <5 after treatment achieved higher serum HBV DNA undetectable rate and serum ALT normalization.However, after withdrawal of antiviral drugs, the mean levels of serum HBV DNA and ALT flared up.CONCLUSION: The intrahepatic HBV DNA load can be significantly inhibited by antiviral agents.The patients with lower levels of intrahepatic HBV DNA have better therapy response. Intrahepatic HBV DNA loss may be a significant marker for the endpoint of antiviral treatment.There is no significant difference in intrahepatic HBV DNA levels between the patients infected with HBV genotype C and genotype B.

Effects of lidocaine on stress reaction for laparoscopic cholecystectomy

PAN Wei-min, WANG Shi-duan, YU Yun-yun, WANG Shi-lei

2007, 12(3):  357-360. 

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AIM: To evaluate the influence of lidocaine on stress reaction.METHODS: Forty-five ASA Ⅰ-Ⅱ patients undergoing laparoscopic cholecystectomy were randomly divided into three groups:In group P anesthesia was induced and maintained with propofol given by TCI;In group L₁ and group L₂ anesthesia was induced and maintained with propofol and lidocaine infusion, loading dose of 1 and 2 mg/kg, respectively, then adding 1 and 2 mg·kg^-1·h^-1 for maintenance inspect.Targeteffect propofol concentration and recovery time were monitored. Plasma hydrocortisone, pancreatic glucagons and angiotensin Ⅱconcentration were determined before induction (T₀), after intubation (T₁), before operation (T₂), before pneumoperitoneum was ended (T₃) and after extraduction (T₄).RESULTS: Target-effect propofol concentration was higher in group P at every time than that in group L₁ and L₂ (P <0.05);Plasma hydrocortisone concentration was lower in group L₂ than that in group P at T₁, T₃ and T₄;Plasma pancreatic glucagons concentration was lower at T₃ and T₄ in group L₁ and L₂ than that in group P;Plasma angiotensin Ⅱconcentration was higher at T₁, T₂, T₃ and T₄ than that at T₀, but there was no difference in three groups.Recovery time was longer in group L₁ and L₂ than that in group P, and it was longer in group L₂ than that in group L₁.CONCLUSION: Lidocaine can decrease the target-effect propofol concentration and the stress reaction in operation, but it prolongs the recovery time.