Table of Content

Volume 12 Issue 8
26 August 2007

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Preliminary discussion on evaluation of bioequivalence for highly variable drugs and drug products

HUANG Qin, WEI Chun-min

2007, 12(8):  841-844. 

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The evaluation of bioequivalence (BE) for highly variable drugs and drug products is an important issue with much concern by industry and regulatory agencies.In this article the authors analyze the difficulties in proving BE when the intrasubject variability is high and introduce several approaches to solve them.The perspectives and suggestions may be very helpful for the domestic BE investigators to focus on this problem and practise more rationally and scientifically.

Effects of genetics variants of pregnant xenobiotic receptor and on pharmacogenetics and drug metabolism

LIU Yan, YIN You, CHEN Yao, ZHOU Hong-hao

2007, 12(8):  845-849. 

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The orphan nuclear receptor PXR influence drug-induced effects indirectly by mediating transcription of genes CYP3A4 and MDR1 which play important roles in drug clearance and disposition.Thus, genetic variability in PXR will contribute significantly to drugdrug interactions in clinical practice.This review describes common PXR genetic variants that have been identified to date in the human population and the functional consequence of these variant alleles.In addition, this article also described alternatively spliced variants of PXR which may also contribute to individual variability as well as tissue specific expression.Identification of PXR genetic variants and alternatively spliced mRNAs may ultimately conduce to the evaluation of rationality when drugs given in combination and the predictions of therapeutic effects.

Pharmacokinetics research progress on statins

DENG Jian-wei, GUO Dong, ZHOU Hong-hao

2007, 12(8):  850-860. 

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Statins are kinds of 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)reductase inhibitors and are widely used for the treatment of hypercholesterolemia. Their efficacy in preventing cardiovascular events has been confirmed by a large number of clinical trials.However, muscular side effects, sometimes severe, including myopathy or rhabdomyolysis, are dose-dependent and associated with the pharmacokinetic alterations of statins. Based on previous studies, pharmacokinetic alterations of statins can be predicted following coadministration of other drugs or in patients with lowered activities in drug metabolism and or transport.To understand the mechanism of the pharmacokinetic alteration, we need the information about the metabolizing enzyme(s)and transporter(s)involved in the pharmacokinetics of statins.In this review, the pharmacokinetic aspects and physicochemical properties of statins are reviewed in order to understand the mechanism governing their pharmacokinetic alterations.

Role of iron in pseudomonas aeruginosa biofilm formation

CAI Yun, NI Shu-xin, LIANG Bei-bei, AN Mao-mao, WANG Rui

2007, 12(8):  861-864. 

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The infection caused by pseudomonas aeruginosa biofilm has becoming one of the most urgent problems in hospital.Recent reports of possible mechanism of iron in biofilm formation were reviewed in this paper.The possible effects of iron on adsorption, microcolony formation, mature of colony and desorb were explained, and the prospect of clinical use of local iron or chelator spray was also reviewed here.

Effects of bupivacaine on intracellular Ca²⁺ in rat ventricular myocytes

ZHU Yi, XU Long-he, ZHANG Hong

2007, 12(8):  865-868. 

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AIM: To observe the effects of bupivacaine at different concentrations on intracellular free Ca²⁺ concentration([Ca²⁺]_i) in isolated rat ventricular myocytes induced by KCl using/Laser scanning confocal microscope(LSCM), and to investigate the mechanism of cardiotoxicity of bupivacaine. METHODS: The cultured ventricular myocytes of newborn rats were divided randomly into 4 groups:the control group (group C), the group of bupivacaine at 10 μmol/L (group B₁), the group of bupivacaine at 50 μmol/L (group B₂) and the group of bupivacaine at 100 μmol/L (group B₃).The fluorescent intensity (FI) of intracellular Ca²⁺ in single cultured cardiomyocytes of newborn rats loaded with Fluo-3 AM was observed by LSCM in order to compare the effects of bupivacaine at different concentrations on the change of [Ca²⁺]_i induced by KCl. RESULTS: There was no difference in the changes of intracellular Ca²⁺ FI in rat ventricular myocytes induced by KCl in group B₁ compared with those in group C(P>0.05).Intracellular Ca²⁺ FI in rat ventricular myocytes induced by KCl was inhibited significantly in group B₂ and B₃ compared with that in group C(P<0.05). CONCLUSION: There is no significant effect of bupivacaine at low concentration on intracellular Ca²⁺ in rat ventricular myocytes induced by KCl.Bupivacaine at high concentraton could significantly inhibit the effects on [Ca²⁺]_i in rat ventricular myocytes induced by KCl.Bupivacaine could inhibit Ca²⁺ transsarcolemmal influx in isolated rat ventricular myocytes dosedependently, which may in part explain its negative inotropic effect.

Apoptosis induced by satraplatin in human ovarian carcinoma cells A2780

YAN Dong-mei, TU Ling-lan, PENG Xiao-ying, LI Wen-jun, SHEN Zheng-rong

2007, 12(8):  869-876. 

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AIM: To observe the growthinhibiting cell cycle-modifying and apoptosis-inducing effects of satraplatin on human ovarian carcinoma cell line A2780, and to explore its possible mechanism. METHODS: The effect of satraplatin on A2780 cells proliferation was determined using MTT, and the change in cell cycle was analyzed using PI staining.Morphologic change was visualized by fluorescence and electron microscopy. AnnexinV-FITC PI staining multiparameter flow cytometry and immuno-histochemical TUNEL assay were used to detect apoptotic cells.The activity of caspase-3 and the effect of pan-caspase inhibitor on cell viability were measured as well. RESULTS: The growthinhibiting and apoptosis-inducing effects of satraplatin were dose-dependent and similar to those of cisplatin.Satraplatin mainly caused A2780 cell accumulation in S phase accompanied by minor accumulation in G₂/M phase.Cells treated with satraplatin exhibited typical morphology of apoptosis.Satraplatin-induced increase in caspase-3 activity of A2780 cells was concentration-dependent.The viability of A2780 cells was affected by pan-caspase inhibitor z-VAD-fmk in a dose-dependent manner under certain concentration of z-VAD-fmk. CONCLUSION: Satraplatin-induced apoptosis in A2780 in vitro was observed.Caspase-dependent and independent pathways were involved in apoptosis induced by satraplatin, and the latter included caspase-3 dependent and non-caspase-3 dependent pathways.

Study on apoptosis of human colorectal carcinoma cell line lovo induced by 5-Fluorouracil and its molecular mechanisms

WANG Suo-an, SONG Qing, ZHANG Xiao-wen, ZHAO Ming, LIU Yong-nian, ZHAO Hai-long, ZHANG Wei

2007, 12(8):  877-882. 

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AIM: To study the molecular mechanism of the cell proliferation inhibition and apoptosis induction effects of 5-Fluorouracil (5-Fu) on human colorectal carcinoma cell line Lovo in vitro. METHODS: By means of MTT reduction assay, the effect of 5-Fu on the proliferation of Lovo cells was measured.Morphological changes were observed under the electron and opitical microscopy. Apoptotic cell cycle arrest was detected by Flow Cytometry.The expressions of PCNA, P53 and Bax were determined by immunohistochemical S-P method. RESULTS: 5-Fu could significantly inhibit the proliferation and aggressivity of Lovo cells and the inhibitory effects were dose-and-time-dependent.The action was mainly attribute to cell apoptosis as proved by flow cytometry assay and electron microscopy.The PCNA expressions of cells of experimental groups were lower than those of control group.The expression of apoptosis related gene bax of the experimental groups was significantly enhanced (P<0.01).The expression of P53 was not found in both experimental and control groups. CONCLUSION: 5-fu could significantly inhibit the proliferation and aggressivity of Lovo cells.Activation of apoptosis related gene bax and G₂/M phase arrest were important mechanisms of 5-fu-induced apoptosis.

Apoptosis-induced effect of solanum lyratum thunb extract on human cervical cancer hela cells

ZHAO Ling-wu, WAN Fu-sheng

2007, 12(8):  883-887. 

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AIM: To investigate the apoptosis-inducing and proliferation inhibition effect of solanum lyratum thunb (SLT) extract and its molecular mechanism on human cervical cancer HeLa cells. METHODS: Dried whole herbs of SLT were extracted by boiling distilled water.Human cervical cancer HeLa cells were randomly divided into the control group, SLT-treated groups (12.5, 25.0, 50.0 mg/mL) and DDP (25.0 mg/L) group. Morphological changes of apoptosis were observed by fluorescence microscope.DNA ladders were examined by DNA agarose gel electrophoresis and the expression of survivin mRNA and caspase-3 mRNA were detected by semiquantitative RT-PCR. RESULTS: SLT extract displayed a strong proliferation inhibitory effect in a dose-and-timedependent manner in HeLa cells.Nuclear shrinkage, chromatin condensation and margination were observed under a fluorescence microscope in HeLa cells treated with SLT extract and DDP.Survivin mRNA levels were down-regulated while caspase-3 were up-regulated. CONCLUSION: SLT extract displays a strong proliferation inhibitory and apoptosis-inducing effect in a doseand-time-dependent manner in HeLa cells.The molecular mechanism of apoptosis of HeLa cells induced by SLT extract has possibly related to up-regulating expression of caspase-3 gene and down-regulating survivin gene.

Delayed protection of limbs atraumatic ischemic preconditioning against myocardial injury in rats

LI Shu-juan, WU Yan-na, KANG Yi, YIN Yong-qiang, GAO Wei-zhen, LIU Yan-xia, LOU Jian-shi

2007, 12(8):  888-891. 

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AIM: To observe the effect of limbs atraumatic ischemic preconditioning (RIP) on the myocardial ischemia-reperfusion (I/R) injury in rats. METHODS: RIP were performed in rats by three cycle of 5 min ischemia-reperfusion of hind limbs once time a day for three days.Animals were divided into four groups:sham, I/R, cardiac ischemia preconditioning (CIP) and RIP group.The effects of RIP on myocardial physiological, the onset and duration of ventricular arrhythmia (VA) and the effect on myocardial infarct size and morphologic change after myocardial I/R 24 h were observed. RESULTS: Compared with sham group, the ST-segment was increased (P<0.01).VA, myocardial infarct size, myocardial swelling, interstitial hemorrhage and inflammatory cell infiltrate were appeared in I/R group.But after pretreated with CIP and RIP, the oxygen demands, the elevation of ST-segment, the duration of VA, the incidence of arrhythmia, myocardial infarct size were decreased (P<0.01), the onset of VA was delayed(P<0.01), and the myocardial swelling, interstitial hemorrhage and inflammatory cell infiltrate were decreased. CONCLUSION: RIP has delayed protection effect against myocardial injury in rats.

Study on anti-tumor mechanism of Chinese medicine Fuzhengyiliufufang by molecular docking method

ZHENG Chun-song, CHEN Li-wu, DU Jian, YE Hong-zhi

2007, 12(8):  892-895. 

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AIM: To investigate the anti-tumor effects of Chinese medicine Fuzhengyiliufufang (FZYLFF) and its mechanism. METHODS: Molecular docking was apllied to simulate the interactions between Chinese medicine small molecules and TNF-α, IL-2 receptors respectively, with the aid of ligand-fit module in the software package Cerius2 4.10 of Accelrys company, to predict the effects of FZYLFF on anti-tumor. RESULTS: According to the dockscore of original ligand and the receptor as threshold value, thirty-seven molecules were predicted to have good interactions with TNF-αand ten molecules with IL-2. CONCLUSION: FZYLFF is a promising Chinese medicine for tumor therapy.Its mechanism is possibly attributed to indirect inhibition by interfering inflammatory cell factors and enhancing immunoregulation.

Experimental study on rosiglitazone reversing myocardial interstitial fibrosis of rats with heart failure

LIU Hong-zhi, GAO Chuan-yu, LEI Jian, LUO Bing, LI Zuo-min, ZHOU Jun,HE Li-qun, QI Ben-ling, CAO Lin-sheng

2007, 12(8):  896-899. 

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AIM: To investigate whether the ligand of peroxisome Proliferator-activated receptor γ(PPARγ), rosiglitazone (ROS), can reverse myocardial interstitial fibrosis in rats with heart failure. METHODS: Sixty weight-matched adult male Wistar rats were randomly divided into 3 groups as follows:(1)the CHF group, in which 2.5 mg/kg of adriamycin (ADR)was weekly injected via a tail vein for 10 weeks (n=25);(2)the ROS group, concomitant ROS and ADR, in which ROS as a PPARγligand was administered by daily gavage at a dose of 3 mg·kg^-1·d^-1(n=25);(3)the control group (n=10).The cardiac function was evaluated by echocardiographic method.The plasma concentrations of TNF-α, Angiotensin II (Ang II)and Aldsterone (Ald)were determined by immunoradiometric assay at 12 weeks after treatment.The hydroxyproline and collagen content were determined by the methods of Chloramines T and Picric acid-Sirius red staining techniques.The pathological change was analyzed by histological hematoxylin-eosin staining. RESULTS: The mortality of ROS-treated rats was significantly lower than that of CHF group (20% versus 40%, P<0.01).The plasma concentrations of TNF-α, Ang II and Ald were higher in the CHF group than those in the control group (P<0.01), which was decreased by ROS treatment.The hydroxyproline and collagen content were increased in CHF group(both P<0.01), but decreased in ROS group.The myocardial collagen of left ventricle increased and the collagen volume fraction (CVF)increased significantly, which were partly reversed by ROS treatment(P<0.01).The pathological results showed there was changes of cardiomyopathy in CHF group, ROS reversed the pathological changes of left ventricular myocardium of CHF. CONCLUSION: Pretreatment with PPARγligand ROS could partly reverse myocardial interstitial fibrosis in rats with heart failure by downregulating the expression of TNF-α, Ang II and Ald.

Effects of mitomycin C on proliferation and apoptosis of fibroblasts derived from keloid

YU Dong-mei, HAO Li-jun, LI Ying, XIAO Zhi-bo, LIU Ying

2007, 12(8):  900-905. 

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AIM: To study the effects of mitomycin C (MMC) on proliferation and apoptosis of fibroblasts derived from keloid. METHODS: Using the cultured fibroblasts derived from keloid subjected to MMC, the proliferation of fibroblasts was detected by MTT.The flow cytometry, microscope and electron microscope were used for evaluation of cell cycles, apoptosis and modality.The expression of cyclin D1 and caspase-3 was detected by RT-PCR and western blotting. RESULTS: MMC inhibited proliferation of fibroblasts in a time-and concentration-dependent manner.MMC changed cell cycles and caused apoptosis in a dose-depended manner and increased the percentage of G₀/G₁ phase cells in fibroblasts.MMC decreased the expression of cyclin D1 and enhanced the expression of caspase-3. CONCLUSION: Changing the expression of cyclin D1 and caspase-3, MMC may play a critical role in suppressing proliferation and inducing apoptosis of fibroblasts to prevention and cure keloid.

Protective effect of Nimodipine on porcine basilar artery oxidative stress injury induced by hydrogen peroxide

CAI Zhi-chun, LI Jian-zhe, CHEN Po-jing, LI Min, WANG Chen-jing, WU Jian-hua, FANG Yun-xiang

2007, 12(8):  906-910. 

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AIM: To study the protective effect of Nimodipine on porcine basilar artery oxidative stress injury induced by hydrogen peroxide (H₂O₂ ). METHODS: Porcine basilar artery rings without endothelium were isolated and allocated in 6 groups:control, H₂O₂ (2×10^-4 mol/L) injury, Vitamin C (10^-4 mol/L) pretreatment, Nimodipine with high, moderate and low dose pretreatment (5×10^-6, 5×10^-7, 5×10^-8mol/L), which were handled with organ chamber technique.The tensive changes after they were treated by vaso-excitor material KCl, phenylephrine and H₂O₂ were compared and the activity changes of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GSH-PX) were detected. RESULTS: (1) Compared with those in the control group, the vascular ring of the H₂O₂ injury group showed more significant contractile response to KCl and phenylephrine.Nimodipine with high, moderate and low doses pretreatment inhibitted the contractile response of the vascular ring to KCl and phenylephrine in dose dependent.(2) Compared with those in the control group, the content of MDA in H₂O₂ injury group was increased, and the activities of SOD, CAT, GSH-PX were degraded.They all have significant difference (P<0.05).Compared with the control group, Nimodipine with high, moderate and low doses pretreatment all degraded the content of MDA, and increased the activity of SOD, CAT, GSH-PX.They all had significant difference (P<0.05). CONCLUSION: Nimodipine can inhibit the contraction of vascular and prevent brain arteria basilaris from injuring.

Preliminary study for narrowing mutant selection window of staphylococcus aureus by combination of levofloxacin and Vancomycin in vitro

LI Zhao-xia, LIU You-ning, WANG Rui, TONG Wei-hang, CHENG Shi-hu

2007, 12(8):  911-914. 

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AIM: To study whether levofloxacin and Vancomycin combination can narrow mutant selection window(MSW)of single drug group in vitro, which contribute to new strategies for restricting the development of resistance and provide data for rational applications of available antibacterial drugs in clinic practice. METHODS: Minimal antibiotic concentration(MPC)and MSWs were determined by spreading 10¹⁰ CFU/mL coccus on agar plates at different drug concentrations.MPC was defined as the lowest concentration inhibiting 100% of the coccus population after 72 h incubation. RESULTS: MSW of levofloxacin and vancomycin for staphylococcus aureus strain ATCC29213 was 16 and 64 respectively;Vancomycin combined with levofloxacin(1MIC+8MIC, 2MIC+ 4MIC)decreased the MSW of levofloxacin to staphylococcus aureus ATCC29213 for 2-4 times;Levofloxacin combined with vancomycin(1MIC+16MIC, 2MIC+8MIC) decreased the MSW of vancomycin to staphylococcus aureus ATCC29213 for 4-8 times. CONCLUSION: Combinations of levofloxacin and vancomycin can decrease MSW to staphylococcus aureus, ATCC29213 compared with individual drug administration.

Effect of atorvastatin on function of carotid artery after adventitia removal in spontaneously hypertensive rats

YANG Hao, WU Ming, WANG Jun-yuan, WANG An-cai

2007, 12(8):  915-919. 

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AIM: To explore the effect of atorvastatin on the function of carotid artery after adventitia removal in SHR. METHODS: 16-week old male SHR (n=36) with left carotid artery adventitia removed were randomly divided into 3 groups (n=12, each):SHR control group, atorvastatin group, valsartan group and the half rats of each group were put to death at the 4th and 8th weeks respectively.The systolic blood pressure (SBP) was assessed before and after treatment with atorvastatin every 2 weeks.The velocity of carotid artery was detected by electromagnetic rheometer while vasotension changes to NE was measured using a force transducer connected with a polygraph. RESULTS: Compared with SHR control group, the SBP of atorvastatin group began declining at the 4th week, and was reduced significantly at the 6th and 8th weeks (P<0.05, P<0.01).The resistance index of carotid artery was reduced significantly in atorvstatin group and valsartan group than that in SHR control group (P<0.05, P<0.01), and it was, at the 4th week, lowered slightly in adventitia removal side than that in normal control side while it was mildly higher at the 8th week, but there was no significant difference between the two sides(P>0.05).Vasotension to NE of carotid artery was reduced significantly after adventitia removal (P<0.01), it was improved by atorvastatin at the 4th week (P<0.01), but decreased mildly at the 8th week(P<0.05). CONCLUSION: Atorvastatin causes a significant reduction of blood pressure in SHR.Adventitia removal makes the vascular resistance of SHR slightly lower at the early stage but higher later, treatment with atorvastatin may lead to decreasement of vascular resistance including the side without adventitia removal.Adventitia removal depresses the vasotension to NE in SHR, the depressed vasotension to NE after adventitia removal can be improved by atorvastatin at the early stage while it can be worsen later.

Effects of N-acetylcysteine on expression of leptin and type Ⅰ collangen in cultured rat hepatic stellate cells

CHEN Yi-ping, WANG Hong-jiao, XIU Zhi-wei, CHEN Jun-ya, SHI Hai-fan, DI Jun-bo, LI Su-hua

2007, 12(8):  920-922. 

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AIM: To study the effects of N-acetylcysteine on the proliferation of rat hepatic stellate cells (HSCs) and the expression variation of leptin and type Ⅰ collagen. METHODS: HSCs were seeded at a density of 1×10⁵ cells mL per well in 96-well plates, which were grouped as follows:NAC Ⅰ, Ⅱ, Ⅲ groups(the concentration of NAC in incubation was 10, 20, 40 mmol/L respectively);Normal saline (NS) was added in the control group.The incubation liquid was extracted after cultured 48 h and was frozen at-20 ℃.Leptin and the synthesis of type Ⅰ collagen were measured by enzyme linked immunosorbent assay(ELISA) and the HSC proliferation was measured by MTT assay. RESULTS: The average absorbance of NAC Ⅲ was signficantly lower than that of the control group(P<0.05).The average type Ⅰ collagen in each NAC group was significantly lower that of the control's(P<0.01). CONCLUSION: HSC proliferation is decreased and the secretion of leptin and type Ⅰ collagen is inhibited after NAC pretreatment.

Therapeutical effects of rhein on nonalcoholic steatohepatitis in rats

LI Rong-zhou, YING Wei-xing, ZHU Chou-wen

2007, 12(8):  923-926. 

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AIM: To explore the therapeutic effect of rhein in rats with nonalcoholic steatohepatitis and its possible mechanism. METHODS: 24 male SD rats were randomly divided into 3 groups after fed with normal diet for 7 days:Control group(n=8), fed with normal diet; Model group(n=8), fed with high-fat and high-cholesterol diet (normal diet plus 10% lard and 2% cholesterol);Intervention group(n=8), rhein was added orally after 12 weeks fed with high-fat and high-cholesterol diet. All the rats were executed after 20 weeks.Body mass, liverweight, transaminase level, blood glucose, triglyceride, cholesteral, insulin level and liver histology were detected.Serum insulin level was measured by radio-immunity technique.The malonaldehyde and glutathione peroxidase activity in live constitution homogenate were measured quantitively. RESULTS: After 20 weeks, the rats in Model group developed lipid metabolic disorder and insulin resistance.The levels of ALT and AST in Model group were higher than those in Control group.Livers presented severe hepatocyte steatosis and the sporadic inflammatory cell infiltration or focal necrosis.There was no significant difference in biochemical index between Intervention group and Control group.Lipid metabolic disorder and insulin resistance of Intervention group were improved, along with the status of hepatocyte steatosis and inflammatory cell infiltration, compared with those in Model group. CONCLUSION: There are significant insulin resistance and lipid metabolic disorder in nonalcoholic steatohepatitis model.Rhein can prevent the development of nonalcoholic steatohepatitis.

Insulin administration on glucose metabolism in alloxan diabetic mice

ZHANG Chao, HU Ya-nan, TANG Li-na, MEI Lin, XIANG Li, LIU Jian-feng, ZHU Li-ping, NIU Hui-sheng, SUN Hong-fan

2007, 12(8):  927-930. 

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AIM: To determine the effect of insulin treatment on oral glucose metabolism in diabetic mice. METHODS: Diabetic mouse model was induced by alloxan and the diabetic mice were given [¹⁴C] glucose by gastric gavage, and then treated with insulin intraperitoneally(IP)or subcutaneously(SC).Diabetic control and the normal control group did not receive any insulin treatment. Glucose and radioactivity in the tail vein blood were detected continually.Mice were sacrificed after 2 hours and radioactivities of the heart, liver and kidney were measured. RESULTS: After given [¹⁴C] glucose by gastric gavage for 2 hours, blood glucose of diabetic control mice was in the hyperglycemic range, but there were no differences among diabetic control, the normal control and the insulin treated diabetic mice(IP, SC)in terms of the radioactivities in the blood.50% of diabetic mice treated with insulin subcutaneously(SC)displayed euglycemia.2 hours after given [¹⁴C] glucose, the radioactivities in liver and kidney of diabetic control were 4 times and 1.5 times that of the normal control separately.The radioactivities in the heart of diabetic control decreased by 70% in comparison with that of the normal control.The radioactivities in liver, kidney and heart of intraperitoneal insulin treated mice (IP)were equal to those in normal mice.The radioactivities in liver and kidney of subcutaneous insulin treated mice with euglycemia (SC-1)were higher than those of the normal control.There was no difference between subcutaneous insulin treated mice with hypoglycemia(SC-2)and the normal control in the radioactivities in liver and kidney.The radioactivity in heart of SC-2 mice group was still lower than that of the normal control. CONCLUSION: These finding indicates that subcutaneous insulin administration, which achieved euglycemia, can not normalize oral glucose metabolism.

Preliminary study on effects of mangiferin on immunologic function in mice

QIN Huai-zhou, WANG Liang, ZHAO Zhen-wei, LI Li-hong, DENG Jian-ping, QU You-zhi, SHI Hang-yu, GAO Li, GAO Guo-doug

2007, 12(8):  931-934. 

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AIM: To investigate the effects of mangiferin purified from leaves of Mangifera indica L.on immunologic function in mice. METHODS: The olig-immunity model was made with hydrocortisone.The indexes of immune organs were calculated.The phagocytosis of mononuclear macrophage was determined with carbon particle clearance test.The spectrophotography was used to detect the levels of serum hemolysis IgG and IgM.The cell proliferation was measured by MTT assay. RESULTS: The mangiferin of 50 and 100 mg/kg significantly increased the phagocytic function, and recovered the indexes of the spleen and thymus in immunosuppressive mice caused by hydrocortisone.It also remarkably increased the levels of serum hemolysis IgG and IgM.The mangiferin could increase the proliferation of mouse spleen cells and macrophage. CONCLUSION: These results suggest that the mangiferin could enhance the non-specific immunity and humoral immunity in immunosuppressive mice.

Determination of paeonol in human plasma by HPLC and its pharmacokinetic studies

WU Jing, WANG Ben-jie, WEI Chun-min, KONG Xiang-lin, GUO Rui-chen

2007, 12(8):  935-938. 

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AIM: To establish a sensitive HPLC method for determining the concentrations of paeonol in human plasma and to evaluate its pharmacokinetic characteristics. METHODS: A single oral dose of 160mg paeonol capsules was given to 24 Chinese healthy volunteers. Paeonol was separated on a XB-C18 column with tetrahydrofuran-methanol-water-phosphonic acid (6:60:34: 0.1, V:V) as mobile phase.The plasma concentrations of paeonol were determined and its pharmacokinetic parameters were calculated and evaluated using DAS 2.0. RESULTS: The linear range of the paeonol was 10-500 ng/mL and the determination limit was 10 ng/mL.The main pharmacokinetic parameters, as C_max, t_max, t_1/2, AUC0-3, AUC_0-∞ after a single dose of paeonol capsules were (116±46) ng/mL, (1.02±0.13) h, (1.03±0.35) h, (174±45) ng/mL, (217±56) ng/mL, respectively. CONCLUSION: The HPLC method for determining paeonol concentration in plasma is rapid, sensitive and suitable for pharmacokinetic studies.

Clinical significance of alpha-fetoprotein detection in HBV infectious related diseases

LU Hai-ying, ZENG Zheng, TIAN Di, CUI Jian-jun, TIAN Guo-bao, TIAN Xiu-lan, YU Min, QIN Xiao-qin

2007, 12(8):  939-942. 

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AIM: To analyze the clinical significance of alpha-fetoprotein(AFP) detection inHBV infectious related diseases. METHODS: The AFP levels in the patients with hepatocellular carcinoma(290 cases), liver cirrhosis(333 cases), chronic hepatitis B (CHB) (361 cases), asymptomatic HBV infection(113 cases) and normal individuals (240 cases) were detected.The logistic regression assay was used to predict the dependent variables which were related to the elevation of AFP. RESULTS: The rates of AFP>20 ng/mL in the five groups were 70.7%, 44.4%, 16.3%, 2.7% and 0%, respectively.The rates of AFP>200 ng/mL were 46.6%, 9.3%, 1.7%, 0.9% and 0%, respectively.The rates of AFP>400 ng/mL were 37.4%, 4.8%, 0.8%, 0% and 0%, respectively.The rates of AFP>1 000 ng/mL were 26.6%, 1.5%, 0.6%, 0% and 0%, respectively. The results of multinomial logistic regression analysis predicted that the variables of age, alcohol drinking quantity and time, CHB, AST, ALT were related to the presence of AFP>20 ng/mL.CHB was related to the presence of AFP>200 ng/mL.AST was related to the presence of AFP>400 ng/mL, and total bilirubin and direct bilirubin were related to the presence of AFP>1 000 ng/mL. CONCLUSION: There are different clinical significance of the AFP levels in different HBV infectious related diseases. The level of AFP is influenced by the factors of age, alcohol drinking, CHB, AST, ALT and bilirubin. The level of AFP more than 400 ng/mL is a significant predictor for the development of hepatocellular carcinoma.

Tolerance study of kaiyuning tablet in healthy Chinese volunteers

WANG Zhi-min, ZHOU Bei-lei, SI Yuan-ping, ZHAI Yi-min, LIU Shan-shan, WANG Chuan-yue

2007, 12(8):  943-948. 

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AIM: To assess tolerance of kaiyuning tablet in healthy Chinese volunteers. METHODS: 28 volunteers were enrolled in a single-dose clinical trial for tolerance study which were randomly divided into 6 groups, including 150, 300, 500, 750, 1 000, 1 250 mg/dosing groups.Another 12 volunteers, randomly divided into two groups of 1 000 and 1 250 mg per day, were enrolled in the multiple-dose clinical trial for 7 consective days.Comparisons were conducted with regard to the clinical symptoms, vital signs and lab examinations acquired before and after dosing in the single-dose and multiple-dose regimens, respectively. RESULTS: No severe adverse events were found in the trial.Common adverse events assiociated with Kaiyuning tablet within the dose range from 150 mg to 1 250 mg including:hypertension, hypotension, dizzinese, drowsinese, headache, facial blushing, dry mouth, nausea, stomachache, constipation, diarrhea, numble in the fingers, transaminase elevation and abnomal ECG.These adverse events were slight and tolerable, which recovered spontaneously following drug discontinuation. CONCLUSION: The results suggest that kaiyuning tablet was safe and tolerable at the dose from 150 to 1 250 mg per day.

Bioequivalence of nicergoline tablets in healthy volunteers

LI Guo-xin, XIA Su-xia, HUANG Dong-cai, WANG Yue-min, TANG Si, ZHANG Yong

2007, 12(8):  949-952. 

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AIM: To study the pharmacokinetics and bioequivalence of nicergoline tablets in healthy volunteers. METHODS: A single oral dose (20 mg test or reference formulation)was given to 20 healthy volunteers according to an open randomized crossover design.10α-methoxy-9, 10-dihydrolysergol(MDL) is a majormetabolite of nicergoline, the concentration of MDL in plasma was determined by LC-MS.The pharmacokinetics parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by DAS program. RESULTS: The main pharmacokinetic parameters of nicergoline tablets were as follows:t_max were (3.3±0.9) and (3.2±0.7) h, t_1/2 were (12.9±4.0) and(12.8±2.4) h, C_max were (23±6) and (22±6) μg/L;AUC_0-t were (291±51) and(282±44) μg·L^-1·h;AUC_0-∞ were (316±50) and (299±46) μg·L^-1·h.The relative bioavailability of two formulations was (104±17)%. CONCLUSION: The two nicergoline formulations are bioequivalent.

Effect of orange juice on talinolol pharmacokinetcs

HE Shan

2007, 12(8):  953-956. 

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AIM: To observe the effect of orange juice on the pharmacokinetics of p-glycoprotein (PGP) substrate drug talinolol. METHODS: 12 healthy adult men were enrolled in this clinical trial with a 2-phase randomized crossover design.In each phase the volunteers received placebo water or 200 mL orange juice 3 times daily for 3 consecutive days, on the fourth day, all subjects took 100 mg talinolol tablet after treated either with orange juice or placebo water one more time, blood samples were collected up to 36 hours with a 7-day washout period.Plasma talinolol were measured by HPLC.Pharmacokinetic parameters between orange juice and placebo water treatment groups were compared. RESULTS: Orange juice treatment reduce the plasma talinolol concentrations, decreases C_max and AUC by 47.6% [(166±44) ng/mL versus (317±119) ng/mL] and 27%[(1783±494) ng·mL^-1·h versus (2456±1048) ng·mL^-1·h].The time to reach maximal talinolol concentration was markedly prolonged, 2.5 h (1.5-4 h) versus 4 h (2.5-6 h), there was no significant difference for half life of talinolol between the two groups(P> 0.05). CONCLUSION: The orange juice substantially reduces the absorption and the bioavailability of talinolol, to such a great extent of the orange juice-talinolol interaction, it is likely to have clinical importance, not only for talinolol, but also for those drugs which share the same transport protein.

Analgesis comparision of morphine administration intravenously and epidurally combined with bupivacaine in postoperative children

JIAO Zhi-hua, ZHANG Xiao-li, LI Jing

2007, 12(8):  957-960. 

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AIM: To compare the analgesic efficacy and safety of intravenous morphine or epidural morphine combined with bupivacaine in postoperative children. METHODS: 48 children scheduled for selective inferior belly or lower limb surgery under general anaesthesia or epidural anesthesia for ASA I or II, age from 3 to 10 years old, were randomly divided into 3 groups(n=16 each).Group A was given intravenous morphine for postoperative analgesia, group B was given epidural morphine in combination with bupivacaine, group C was given nonsteroidal anti-inflammatory drugs orally or pethidine intramuscularly in need as the control group.When the patients were fully awake in the recovery area, heart rate (HR), blood pressure, peripheral oxygen saturation (SpO₂), respiratory rate and pain were recorded at 2, 4, 8, 12, 24 and 48 h postoperatively, side-effects were also noted.Pain was assessed using an objective pain score (OPS). RESULTS: There was no significant difference of OPS between group A and B, and the efficacy and duration of analgesia in group A and B were significantly better than those in group C (P<0.05).The incidence of drowsiness, nausea and vomiting was higher in group A than that in the other 2 groups. CONCLUSION: Intravenous morphine or epidural morphine in combination with bupivacaine are both effective for postoperative analgesia in children.Epidural group outweigh intravenous group in terms of its lower incidence of side-effects.