Table of Content

Volume 9 Issue 4
26 April 2004

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Application of epidermal growth factor receptor tyrosine kinase inhibitors in cancer therapy

LI Zhe, YUAN Shou-Jun

2004, 9(4):  361-364. 

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Epidermal growth factor receptor (EGFR) tyrosine kinase is over-expressed in numerous human tumors, which plays pivotal roles in cellular signal transduction, and it is involved in a variety of tumor cellular behaviors such as proliferation, metastasis, angiogenesis and so on.Many investigations have indicated that tumor growth can be suppressed by inhibiting EGFR tyrosine kinase activity.Currently, several EGFR tyrosine kinase inhibitors are in clinical trial stage.

Evaluation on selective probes for CYP3A

ZHU Xue-Hui, LOU Jian-Shi

2004, 9(4):  365-369. 

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Ideal probes for CYP3A can provide instruction for rationally clinical drug use.Comprehensive comparison and analysis were used for the present probes to evaluate the applicative characteristics of different selective probes for CYP3A and to indicate clinical value in rational drug therapy.Among the series of CYP3A probes, midazolam is considered the best one.

Research progress of small low-density lipoprotein

QIN Yan-Wen, WANG Lu-Ya

2004, 9(4):  370-373. 

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Low-density lipoproteins are hererogeneous in terms of size and density.The presence of sLDL is associated with raised triglyceride and may be a risk marker for coronary artery disease.Small dense LDL particles have been proved to be more atherogenic than large LDL particles.Antioxidant content of sLDL decresed in comparson with large and buoyant LDL, can enhance the expression of cell adhesion molecules.This property may be proposed to contribute to increase disease risk of atherogenic.

Blood pressure regulation of statins

XIE Xiao-Jing, WANG An-Cai

2004, 9(4):  374-377. 

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Statins is first choice of hypercholesteroiemia.Recently, clinical investigations have shown that statins can correct blood pressure in hypertension patients accompanied with lipid abnormalities.This result can be observed not only in untreated patients but also in patients treated with antihypertensive drugs.But some researches did not support this result completely.To some extend, the mechanisms responsible for the hypotensive effect seem to be largely independent on the effect of statins on lipid profile, and may be related to the improvement of endothelial function and the regulation of angiotensin II receptors.

Effects of new ATP-sensitive potassium channel pener iptakalim on Parkinsonian symptoms induced by haloperidol in rats

LONG Yan, YANG Yong, DING Jian-Hua, HU Gang

2004, 9(4):  378-381. 

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AIM: To investigate the effects of the new K_ATP channel opener, I_ptakalim (I_pt), on the Parkinsonian symptoms induced by haloperidol in rats. METHODS: Using L-DOPA as the positive drug, the influences of I_pt on latency time, walking time, rearing and grooming of the parkinsonian-like rats induced by haloperidol were observed.RESULTS: I_pt ameliorated hypolocomotion and assuaged catalepsy induced by haloperidol in rats. Moreover, the effects of I_pt (0.5 mg·kg^-1) were better than those of L-DOPA (100 mg·kg^-1).CONCLUSION: Opening of K_ATP channels may play a key role in improving Parkinsonian symptoms induced by haloperidol in rats.

Effects of iptakalim hydrochloride on secretion function of blood vessel endothelial cells

JIA Guo-Dong, LIU Guo-Shu, WANG Hai

2004, 9(4):  382-385. 

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AIM: To study the effects of the novel antihypertensive drug I_ptakalim hydrochloride (I_pt) on the secretion function of blood vessel endothelial cells. METHODS: Bovine aortic endothelial cells (BAEC) were obtained by using digestion technique.Effects of I_pt on the endothelin-1 (ET-1), prostacyclin (PGI₂) and nitric oxide (NO) secretion by BAEC were studied and effects of I_pt on the intracellular calcium concentration in BAEC were examined by miocrofluorometry of Fura-2/AM loaded cells.RESULTS: I_pt at 10^-6 mol·L^-1 or more could inhibit cultured bovine aortic endothelial cells from producing and releasing endothelin-1 in a concentrationdependent manner, together with an increase in NO production.Moreover, I_pt at 10^-4 mol·L^-1 or more induced a rapid elevation of intracellular calcium concentration in BAEC.CONCLUSION: I_pt can improve the balance between the release of relaxing and contracting factors from the endothelium by inhibiting ET-1 production and enhancing NO production in BAEC.The elevation effect of [ Ca²⁺] i by I_pt is essential for the cytoplasm synthesis of NO, and the effect may favorably enhance endotheliummediated dilation.

Protective effect of Cordyceps sinensis extract on acute lung injury induced by lipopolysaccharide in mice

DAI Ying, ZHANG Bin, ZHOU Yong, CHENG Xin-Rui, DU Guan-Hua

2004, 9(4):  386-388. 

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AIM: To study the effects of Cordyceps sinensis extract on experimental acute lung injury model in mice.METHODS: Acute lung injury model was induced by intratracheal instillating lipopolysaccharide (LPS, 2.4 mg·kg^-1) in mice.The mice were given Cordyceps sinensis extract (ig, 10, 30 mg·kg^-1) in 4 and 8 h after receiving LPS.The cell counts in the blood and bronchoalveolar lavage (BAL), the protease activity and the protein concentration in BAL were measured.RESULTS: Cordyceps sinensis extract could decrease the number of leukocyte and neutrophil, and increase the counts of lymphocyte and monocyte.The activity of protease was significantly depressed by the preparation. CONCLUSION: Cordyceps sinensis extract shows protective effect on the acute injured lung in mice.

Effects of Iptkalim hydrochloride on mRNA level of ATP-sensitive potassium channels of pulmonary artery smooth muscles in chronic hypoxic rats

SHEN Hong, WANG Hong, XIE Wei-Ping, HU Gang

2004, 9(4):  389-393. 

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AIM: To study mRNA expression of ATP-sensitive potassium channels (K_ATP) of pulmonary artery in chronic hypoxic pulmonary artery hypertension (CHPAH) rats and in chronic hypoxic rats treated with novel K_ATP opener Iptkalim hydrochloride.METHODS: Sixteen Sprague-Dawley(SD) male rats were randomly divided into control group, hypoxic group, low dose Iptkalim group (0.75 mg·kg^-1·d^-1), and high dose Ipkalim group (1.5 mg·kg^-1 ·d^-1).Except the first group, the other three groups were put into hypoxic and normobaric chamber to establish chronic hypoxic model.Four weeks later, reverse transcription polymerase chain reaction (RT-PCR) was performed to analyze the mRNA level of K_ATP channels in pulmonary main artery smooth muscles. RESULTS: The mRNA levels of SUR2 in the hypoxic group were significantly lower than those in the control group, this decrease was completely reversed by Iptkalim in high dose group, and no difference in Kir 6.1 mRNA level was found between four groups.CONCLUSION: K_ATP channel transcriptional expression is inhibited by chronic hypoxia, and this inhibition can be up-regulated by Iptkalim.The role of potassium channel in the development of CHPAH may explain the therapeutic mechanism of Iptkalim.

Effects of Peucedanum praeruptorum Dunn Extract on left ventricular remodeling and Bcl-2, Bax protein expression in aorta coarctation rats

TU Xin, WANG Jin-Ming, TU Qian, TU Jin-Wen

2004, 9(4):  394-398. 

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AIM: To investigate the effects of Peucedanum praeruptorum Dunn Extract on left ventricular remodeling and apoptosis-related protein(Bcl-2, Bax) expression in aorta coarctation rats.METHODS: Partly aorta coarctation was practiced in Wistar rats.The weight of the left ventricular and the cardiac index were measured;the diameter of the left ventricular cavity was measured by means of HE dyeing;the expression of Bcl-2 and Bax protein in myocardium was observed by immunohistochemical method.RESULTS: After partly aorta coarctation, the weight of the left ventricular and the cardiac index of rats were increased significantly.Compared with the model group, 400 % PdE decreased the left ventricular and the cardiac index effectively and 200 % PdE decreased the increasing cardiac index in rats which after aorta coarctation.In the model group, the myocardial cells were much bigger and there were much more parallel connections and series connections of sarcomere;compared with those in the model group, the myocardial cells were nearly normal or just had a slight degree of hypertrophy and hyperplasia in both 400 % PdE and 200 % PdE groups.Compared with the model group, the 400 % PdE and 200 %PdE groups had bigger diameter of left ventricular cavity, the difference was significant (P <0.05); compared with the model group, 400 % and 200 % PdE significantly increased the proportion of Bcl-2 and Bax protein expression in the myocardial cells of rats after the aorta coarctation.CONCLUSION: Peucedanum praeruptorum Dunn Extract can affect the remodeling process of ventricular muscles and the apoptosis-related proteins in different ways and had positive importance in treatment of ventricular remodeling.Therefore, it deserves further researching and developing.

Comparison of effects of three drugs for Alzheimer's disease on viability of mouse cortical neurons in vitro

XIONG Xiao-Yun, WU Yu-Mei, ZOU Yong, LIU Ji-Xiang, HU Jian-Ping, HE Jian, MEI Qi-Bing

2004, 9(4):  399-402. 

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AIM: To observe and compare the effects of three drugs for Alzheimer's disease on viability of mouse cortical neurons in vitro including memantine hydrochloride, metrifonate and resveratrol in order to provide experimental data for screening out a better lead compound.METHODS: Mouse cortex neurons were isolated from embryo mice (E15)and plated on 96-well cultureplates with drugs in the serum medium.The effects of different concentrations of drugs on neuron viability were determined by MTT.Phase contrast microscopy and immunocytochemical method were used to examine the influence of drugs on the morphology of the neurons.RESULTS: Memantine hydrochloride enhanced the viability of neurons in a dose dependant way.Metrifonate had no effect but inhibited the effect on the viability of neurons at high concentrations(0.1, 1 μmol·L^-1).Resveratrol enhanced the viability of neurons at low dose (0.1 nmol·L^-1), while inhibited the viability of neurons at high dose(0.1,1, 10 μmol·L^-1).CONCLUSION: It is feasible that memantine hydrochloride can be regarded as the lead compound to design more potential drugs for Alzheimer's disease.

A novel antisense oligodeoxynucleotide-doxorubicin conjugate against the multidrug resistance gene mdr1:inhibition to KB-A-1 cell and P-glycoprotein expression

ZHAN Xiao-Yun, REN Yu-Hong, ZHANG Qiang, LU Yan-Hua, WEI Dong-Zhi, LIU Jian-Wen

2004, 9(4):  403-410. 

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AIM: Over-expression of P-glycoprotein (P-gp) on the surface of tumor cells that works as a membrane pump enhancing the drug efflux is regarded as a main candidate mechanism of multidrug resistance (MDR).And mdr1 is one of the two main genes that encode P-gp in human cells.In this study, a novel conjugate made of mdr1-anti-sense oligodeoxynucleotide (ODN) and a potent anticancer drug doxorubicin was constructed.The cytotoxicity of the conjugate as well as the effect of the conjugate on the modulation of P-gp-mediated MDR in KB-A-1 cell lines was studied.The molecular mechanism of its regulation effect was also investigated. METHODS: Multidrug resistant KB-A-1 cell lines were used.MTT was applied to measure the cytotoxicity of the conjugate and doxorubicin to KB-A-1 cells. Effect of the conjugate on intracellular doxorubicin accumulation was determined by HPLC.RT-PCR and Western blot were used to determine the expression of mdr1 gene and P-glycoprotein in KB-A-1 cells.RESULTS: The results showed that the conjugate exhibited more cytotoxicity than ODN, and also it could promote the cytotoxicity of doxorubicin to KB-A-1 cells.The IC50 of doxorubicin dropped from 24 to 18 μg·ml^-1.The results of RT-PCR and Western blot analysis illuminated that conjugate might down-regulate the P-gp expression.CONCLUSION: All the findings suggest that the conjugate is more potential for efficient reversal of MDR phenomenon than free ODN. The study indicated that such a conjugate should be a new feasible and efficient anti-sense reagent both in lab research and further in clinical therapy.

Study of 17 β-Estradiol supplementation on increasing eNOS expression and NO production in ovariectomized rat heart

TANG Yong-Bo, WANG Qian-Lei, ZHU Bing-Yang, HUANG Hong-Lin, LIAO Duan-Fang

2004, 9(4):  411-416. 

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AIM: To investigate whether 17β-estradiol influences the production of nitric oxide (NO) and expression of eNOS in ovariectomized (OVX) rats heart. METHODS: Female mature Sprague–Dawley rats were subjected to a bilateral ovariectomy, and sham operation as control.OVX rats were randomly assigned to the following treatments:17β-estradiol (100 μg·kg^-1 in 100 μl sesame oil sc daily), 17β-estradiol vehicle (100 μl sesame oil sc daily) and OVX control.The treatment lasted 6 weeks.Blood pressure, heart rate, plasma estradiol, uterine weights and nitrite production in the myocardium were studied.Western blot analysis was used to assay the protein expression of eNOS and caveolin-1.RESULTS: The heat rates in 17β-estradiol treatment group (314 ±16 beats·min^-1) were lower than those in other groups (P <0.05).Compared with vehicle group, nitrite production increased one fold in the hearts of E2 treatment group, the abundance of eNOS protein showed a significant increase (P <0.01).Concurrently caveolin-1 protein, an endogenous eNOS inhibitor, protein expression abundance was significantly decreased (P <0.05) in the E2 supplement group.CONCLUSION: Estrogen supplementation directly increases eNOS functional activity and NO production in rat heart, this effect may be related to estrogen-induced deceasing of heart rates.

Comparison of zinc gluconate and zinc fructose-1, 6-diphosphate on pharmacokinetics in mice

LUO Huan-Min, WANG Cheng-Xi, GAO Qin, XIAO Fei, WENG Wen, ZHANG Pei-Fen, LI Xiao-Guang

2004, 9(4):  417-419. 

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AIM: To compare pharmacokinetic character between zinc gluconate (Zn-G)and zinc fructose-1, 6-diphosphate(Zn-FDP)in mice.METHODS: Inductively coupled plasma (ICP)was used to measure the zinc serum concentration at regular time-points in mice, and the pharmacokinetic parameters of both drugs were calculated. RESULTS: The values of Ke (h^-1)of Zn-FDP and Zn-G were 0.27 ±0.12 and 0.41 ±0.03, respectively;the t_max(h), 1.65 ±0.04 and 1.43 ±0.05;the C_max (mg·L^-1), 9.27 ±0.25 and 13.46 ±0.16;and AUC (mg·h^-1·L^-1), 47.45 ±2.11 and 57.67 ±5.80. CONCLUSION: The blood zinc content after Zn-FDP orally administered is lower than that one after Zn-G, but there is no significance in the zinc content differences among heart, liver, brain and kidney, suggesting that Zn-FDP is not as good as Zn-G in absorption.

Effects of tetramethylpyrazine on proliferation of rat glomerular mesangial cells induced by lipopolysaccharide and levels of intercellular adhesion molecule-1

WANG Xia, LI Qi-Xiong

2004, 9(4):  420-422. 

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AIM: To investigate the effects of tetramethylpyrazine (TMP) on the proliferation of rat glomerular mesangial cells (GMCs) induced by LPS and the levels of intercellular adhesion molecule-1 (I CAM-1).METHODS: Different concentrations of TMP were put in the cultured rat GMCs in vitro after induced by LPS.Cell proliferation was assessed by MTT colorimetric assay and cell cycle was analyzed by flow cytometry.The levels of ICAM-1 were detected by immunohistology.RESULTS: The proliferation of MC induced by LPS was inhibited significantly by TMP with a dose-dependant manner.In the cell cycle, TMP increased the cells in G₀/G₁ phase and decreased the cells in S phase, and the ICAM-1 expression level was decreased.CONCLUSION: LPS-induced proliferation of MC is inhabited significantly by TMP.It blocks G₀/G₁ phase into S phase and inhibited the ICAM-1 expression.

Clinical evaluation of the effect of therapy of kidney tonification and blood activation on patients with chronic aplastic anemia

ZHANG Xiao-Hui, LIANG Feng-Zhen

2004, 9(4):  423-425. 

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AIM: To evaluate the effect of therapy of “kidney tonification and blood activation” on patients with chronic aplastic anemia (CAA).METHODS: 60 CAA patients were randomly assigned to treatment group and control group, with the former given traditional Chinese medicine for tonifying kidney and activating blood and the latter given CAA hematogenetic tablets.The levels of IL-2 and IL-8 were compared with those before and after the treatments and another 18 cases as normal group.RESULTS: Patients from treatment group and control group were cured with remission rate 66.67 % and 40.00 %, respectively.Treatment group was superior to control group in effectiveness(P <0.05).The positive indexes of IL-2 and IL-8 before treatment were both higher than those of normal group (P <0.05), while after treatment they decreased (P <0.05).CONCLUSION: The therapy for tonifying kidney and activating blood can reduce the secretion of IL-2 and IL-8 in CAA patients, and promote the restoration of hematogenetic function.

Combined therapeutic effects of recombinant human IL-10 with soluble chicken type Ⅱ collagen on experimental arthritis

LU Yan-Xu, CHEN Min-Zhu, LU Jing-Tao

2004, 9(4):  426-429. 

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AIM: To investigate the combined therapeutic effects of recombinant human interleukin-10 (rhIL-10) with soluble chicken collagen type Ⅱ (SCC Ⅱ) on rat adjuvant arthritis(AA).METHODS: The paw swelling, gain in body weight, thymus-and spleen-indices, the lymphocyte proliferative responses induced by ConA and the levels of IL-1 in the peritoneal macrophages (PMΦ) and synovial membrane tissue cells (SMCs) in rats were examined. RESULTS: Compared with SCC Ⅱ (0.03 mg·kg^-1 ·d^-1, ig) or rhIL-10 (1, 2 μg·d^-1, sc) treatment alone, combined treatment of rhIL-10 (1,2 μg·d^-1, sc) with SCC Ⅱ (0.03 mg·kg^-1·d^-1, ig) significantly improved the above indices, shortened the induced phase of rat oral tolerance (OT) to SCC Ⅱ, and strengthened the treatment effect.CONCLUSION: rhIL-10 can improve the therapeutic effect of SCC Ⅱon rat AA.

Therapeusis of arsenic trioxide on asthma in mice and its possible mechanisms

QIN Dong-Yun, LIANG Biao

2004, 9(4):  430-433. 

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AIM: To study the therapeusis of arsenic trioxide on asthma and the effects of arsenic on T cell cycle and Bcl-2 expression in asthmatic mice.METHODS: 49 healthy Kunming male mice at 5 wk of age were randomly divided into 7 groups:control group, asthmatic group, dexamethasone group and arsenic group (the mice were given arsenic trioxide 0.575, 1.15, 2.3, and 4.6 mg·kg^-1 before challenge).An animal model of asthma was established by means of OVA sensitizing-challenging.Pulmonary functions in those mice were measured by Organism Signal Collection System software.Total leucocytes and its cell classification, protein concentrations, and pulmonary function were detected.CD3 expression, T cell cycle and Bcl-2 expression were detected by flow cytometry.RESULTS: In those groups treated with arsenic trioxide, compared with asthmatic group, the pulmonary function improved, the count of total leucocytes, eosinophils, lymphocytes and protein concentrations decreased.There were double effects of arsenic trioxide on T cell in spleen: induction apotosis in the dose of 1.15 mg·kg^-1, inhibition proliferation and activation in the dose of 4.6 mg·kg^-1.The Bcl-2 expression in every group treated with arsenic trioxide was lower than that of asthmatic group, and the effect was in a dose-dependent manner.CONCLUSION: There are therapeutic effects of arsenic trioxide on asthma.The mechanisms may be ascribed to the effects of arsenic trioxide on apotosis and activation and the Bcl-2 expression of T cells.

Protective effects of deproteinized extract of calf blood on hypoxia-reoxygenation-induced injury in cultured myocardial cells

YANG Yu-Hong, LOU Feng-Xia, WANG Hong-Xin

2004, 9(4):  434-437. 

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AIM: To explore the effects of DECB (deproteinized extract of calf blood, DECB) on hypoxiareoxygenation-induced injury in cultured cardiac myocytes.METHODS: By using cultured myocardial cells as models, thenumber of death cells, beating frequency and the content of LDH were observed after hypoxia-reoxygenation-induced injury. RESULTS: 0.1 and 0.3 g·L^-1 of DECB decreased the number of death cells and the content of lactate dehydrogenase (LDH), and restored the cellular beating frequency in the supernatant. CONCLUSION: DECB can protect the cultured myocardial cells against hypoxia-reoxygenation-induced injury.

Comparison of paclitaxel containing platinum and cyclophosphamide containing platinum chemotherapy in women with advanced epithelial ovarian cancer

LI Cong-Zhu, ZHAI Yu-Xia, HUANG Ping, ZHOU Li, XU Lan, LI Yan

2004, 9(4):  438-440. 

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AIM: To compare the therapeutic effect of paclitaxel containing platinum (cisplatin or carboplatin) and cyclophosphamide containing platinum chemotherapy in women with epithelial ovarian cancer.METHODS: 24 cases with advanced epithelial ovarian cancer after initial surgery received paclitaxel and cisplatin or carboplati.Paclitaxel (135 mg·m^-2, over a period of 3 hours) was administered iv once every 3 to 4 weeks, in comparison with those 30 cases treated with “CAP ” or “CVP” regimen.RESULTS: The overall median survival time was significantly longer in the paclitaxel-platinum group than that in the cisplatin-cyclophosphamide group (median 41.5 vs 32.6 mon, P <0.01).Among 24 women with measurable disease, 75 percents in the “TP” group responded to the therapy, comparing with 40 percent in the “CP” group (P <0.05).CONCLUSION: Paclitaxel and platinum agent is more effective than “CP” regimen in the treatment of patients with advanced epithelial ovarian cancer.

Effects of four Chinese herbs which pass through liver-channel on improving eyesight and protecting oxidative injury of lens and apoptosis of lens epithelial cells

HUANG Xiu-Rong, QI Ming-Xin, WANG Zhao-Yang, WANG Yong

2004, 9(4):  441-446. 

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AIM: To study effects of four Chinese herbs i.e.Semem Plantaginis (SP), Semem Celosiae (SC), Flos Chrysanthemi (FC) and Radix Rehmanniae Preparata (RRP), which pass through liver-channel on improving eyesight and protecting oxidative injury of lens and apoptosis of lens epithelial cell (LEC).METHODS: 21 New Zealand rabbits (42 lenses) were divided randomly into 7 groups:control group, Fenton group, Pirinoxine odium (PS) group and four Chinese herbs (SP, SC, FC and RRP) groups.Lens oxidative injury models were induced by Fenton reaction.Lens opacities were observed via surgical microscope.The contents of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total protein (TP), and soluble protein (SP) in all lenses were measured.21 Sprague-Dawley rats (42 lenses) were divided randomly into above 7 groups.Apoptosis of LEC were induced by H₂O₂.The rates of LEC apoptosis in all groups were detected by terminal deoxynucleotidyl transferase mediated biotin-dUTP nick end labeling (TUNEL), and the morphological changes were observed by transmission electron microscope.RESULTS: Lens opacities in groups of four Chinese herbs (SP, SC, FC and RRP) were much lighter than that in Fenton groups.The contents of SOD, GSH, and GSH-Px in lenses of four Chinese herb groups were higher than Fenton groups (P <0.01).The rates of LEC apoptosis in lenses of four Chinese herb groups (16.0 ± 2.8, 30.0 ±2.3, 21.0 ±2.5, 43.1 ±3.5) were significantly lower than that in H₂O₂ (92.0 ±2.55) and PS (56.0 ±9.9) group (P <0.05).The ultrastructure study indicated that the most LEC in H₂O₂ group showed apoptosis and there were in any stages of apoptosis observed by transmission electron microscope.Apoptosis cells in LEC of four Chinese herb groups were much less than that in H₂O₂ group and PS group, and the apoptosis changes of cells were in early or middle stages.CONCLUSION: The four Chinese herbs can obviously increase anti-oxidative ability, protect oxidative damages, alleviate opacities of lenses, and inhibit LEC apoptosis, which are better than that of PS.

Effects of spironolactone on cardiac function and serum brain natriuretic peptide levels in patients with chronic heart failure

CHEN Xie-Xing, HONG Hua-Shan, CHEN Liang-Long, WANG Yi-Bo, YE Ming-Fang, JIANG Qiong

2004, 9(4):  447-450. 

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AIM: To investigate the effects of spironolactone on cardiac function and serum brain natriuretic peptide (BNP) level in patients with chronic heart failure (CHF).METHODS: 42 patients with CHF, defined as New York Heart Association (NYHA) functional classes Ⅱ-Ⅳ, received medication of diuretic, digitalis and angiotensin-converting enzyme inhibitor.The patients were randomly divided into the treatment group (extra spironolactone 20 mg daily, n =21) and the control group (n =21).The changes of NYHA functional class were evaluated before and after the treatment for 1 mon.The levels of BNP-32 in serum were measured by immunoradiometric assay immediately after administration.Left ventricular ejection fraction (LVEF) and left ventricular internal dimension at end-diastole (LVED) were measured by M-mode Echocardiography.BNP, LVEF and LVED were re-checked 3 mon later.RESULTS: The total effective rates were 85.7 % in the spironolactone group and 76.2 % in the control group (P <0.05), and the evident effective rates were 61.9 % in the spironolactone group and 42.9 %in the control group (P <0.05).Spironolactone significantly decreased NYHA functional class (P <0.05) after 1 mon therapy in patients of the treatment group, which had no difference from the control group.Spironolactone significantly increased LVEF (P < 0.05), and decreased LVED (P <0.05) after 3 mon therapy in patients of the treatment group, but had no difference in those of the control group.There were significantly attenuated BNP levels in patients with CHF between two groups (P <0.05), but were more decreased in the spironolactone group (P <0.01).Changes in BNP levels were significant negative correlation with CHF patients in the spironolactone group after medication in LVEF (r =-0.42, P <0.05), and significant positive correlation with those in LVED (r =0.60, P <0.05). CONCLUSION: Spironolactone can not only improve left ventricular remodeling and cardiac function but also lower BNP levels in CHF patients.Serum BNP level may serve as a therapeutic indicator for spironolactone treatmemt in CHF patients.

Study of pharmacokinetics of diclofenac sodium sustained-released suppository in Chinese healthy volunteers

HU Ai-Ping, HU Guo-Xin, QIU Xiang-Jun, DAI Zong-Shun

2004, 9(4):  451-454. 

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AIM: To study the pharmacokinetics of diclofenac sodium sustained-released suppository in healthy volunteers.METHODS: A single dose of 100 mg diclofenac sodium sustained-released suppository was given to 20 healthy volunteers.The concentrations of diclofenac sodium sustained-released suppository in plasma were determined by HPLC method.The parameters of pharmacokinetics were calculated by 3p87 program.RESULTS: The C_max of the drug was 1.1 ±0.310 mg·L ^-1; T_max was 1.7 ±0.167 h;T_1/2(ke) was 2.3 ±0.6 h;CL was 27 ±6 L·h ^-1;V_d was 74 ±25 L;AUC_0-∞ was 4.0 ±1.2 mg·h ^-1·L ^-1.CONCLUSION: The pharmacokinetics of this drug in healthy volunteers can be fitted into one compartment model with 1st order absorption.

Relationship between protective effect and antioxidative action of rutosid on experimental acute pancreatitis in rats

TIAN Jie, SONG Shao-Gang, CHEN Zhi-Wu, ZHAO Wei-Zhong

2004, 9(4):  455-458. 

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AIM: To study the protective effect and the antioxidative action of rutoside (Ru) on experimental acute pancreatitis (AP) in rats.METHODS: AP model was induced by retrograde injection of sodium deoxycholate into bilipancreatic duct in rats.The amylase (AMS) activity and the nitric oxide (NO) level in serum were measured at 6 and 12 h after the induction of AP. The superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content in pancreas tissue were measured at 24 h after the induction.Meanwhile, the pathologic change of pancrease at 24 h after the induction was observed.RESULTS: Ru (30, 60, and 120 mg·kg^-1, sc) could decrease the serum levels of AMS and NO significantly, attenuate the pathologic leision of pancrease, enhance the SOD activity and reduce the MDA production in the pancreas tissue.CONCLUSION: Ru has certain protective effect on AP in rats by administrating subcutaneously.The mechanisms may be due to strengthening endogenous antioxidative system and the ability of scavenging oxygen-derived free radicals (OFR), improving the histophysiology of AP and attenuating the injury of pancreas.

Experimental study on analgesic efficacy of Corydalis suppositories

LI Jian-Chun, HUANG Ji-Han, GUI Chang-Qing, ZHENG Qing-Shan

2004, 9(4):  459-463. 

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AIM: To investigate the analgesic efficacy of Corydalis suppositories.METHODS: Rats and mice aching models given different doses of Corydalis suppositories by rectum were established to observe the analgesic efficacy;the influence of the Corydalis suppositories was recorded on the frequency, range andmotoricity of uterine smooth muscle in vitro.RESULTS: Compared to control group, Corydalis suppositories enhanced pain threshold, delayed latent period, decreased mumber of times and twisting bodies incidence of animals, and weakened frequency, range and motoricity of uterine smooth muscle in vitro induced by pitocin.CONCLUSION: Corydalis suppositories can relieve the pain of various aching models and resists the acute contraction induced by oxytocin.

Effects and evaluation of misoprostol in hysteroscopy

LIN Qiong-Xia, ZHEN Qiao-Li, XU Lan

2004, 9(4):  464-466. 

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AIM: To observe the effects of misoprostol used for intenerating cervical and ease pain in hysteroscopy.METHODS: 63 of 107 cases were randomly chosen as the group of misoprostol, and 200 μg misoprostol was taken orally 1h before hysteroscopy.Another 44 cases were taken as the group of antitheses, and no medication was taken before hysteroscopy.RESULTS: The diameter of cervical, hemorrhage, the rate of PAAS and bellyache in the group of misoprostol were lower than that in the group of antitheses.CONCLUSION: 200 μg misoprotol orally 1h before hysteroscopy is an advantageous and ideal method with alleviating pain from wound, reducing manipulation, decreasing hemorrhage, reducing PAAS happening in intenerating cervical.

Changes of c-fos mRNA in rabbits hippocampus during different anesthetic depths using target-controlled infusion of propofol

CHEN Jian-Yan, YAO Shang-Long, ZENG Bang-Xiong

2004, 9(4):  467-469. 

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AIM: To research alterations of c-fos mRNA in rabbit hippocampus during propofol anesthesia. METHODS: 30 rabbits randomly allocated into 3 groups:control group, shallow anesthetic group and deep anesthetic group.Each group had 10 rabbits.The expression levels of c-fos mRNA in different anesthetic depths in hippocampal CA1, CA3, and DG were observed using target-controlled infusion of propofol.RESULTS: As the anesthetic depth increased, the levels of c-fos mRNA in hippocampal CA1 and DG increased significantly compared with control group.The levels of c-fos mRNA in hippocampal CA3 had no significant change in all groups. CONCLUSION: Propofol affects the expression of c-fos mRNA, subsequently influences fos-related gene transcription and its anesthetic action.The influence differs in different brain regions.

Selection of combined drugs in patients with hypertension inadequately controlled by benazepril alone:compare the Bp-reducing effects of combination of benazepril and levamlodipine with those of benazepril and nifedepine sustained-release tablet

JIA Ming, PAN Qi-Hong, ZHU Zi-Feng, HUANG Lin-Shu, WANG Ying

2004, 9(4):  470-473. 

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AIM: To compare the therapy of the combination of benazepril and levamlodipine (B/LA) with benazepriland and nifedepine sustained-release tablet (B/NSr) in patients with mild to moderate hypertension inadequately controlled by benazepril alone.METHODS: Experiments were performed in 112 patients with primary hypertension inadequately controlled by benazepril alone. The patients were randomized divided into two groups. Continued previous benazepril treatment, the B/LA group (n =56) was added levamlodipine, 2.5 mg once daily for 2 weeks, the B/NSr group (n =56) was added nifedepine sustained-release tablets, 10 mg once daily for 2 weeks.Examinations were performed before and at the end of 2 weeks of combination-treatment period.The total combination-treatment period was 4-6 weeks.RESULTS: The overall Bp-reducing efficacious rate of LA/B group was 85.71 %, and that of LA/B group was 78.57 % (P >0.05), but the obvious Bp-reducing rate in B/LA group was 73.21 %, which was significantly higher than that in B/NSr group (57.14 %, P <0.05). The adverse effects rate was 8.93 % in B/LA group and 21.43 % in B/NSr group (P <0.01).CONCLUSION: Either LA/B or B/NSr is effective in the treatment of hypertension inadequately controlled by benazepril alone, but LA/B is more desirable therapy than B/NSr.

Procedures for investigators training in institutions for clinical trials

WANG Yi-Bing, XIONG Ning-Ning, BO Qing-Yan, JIANG Meng, LIU Fang, ZHOU Jian-Dong, FU Wei-Min

2004, 9(4):  474-476. 

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Qualified investigators play a key role in guaranteeing the quality of clinical trials.Receiving training programs arranged by clinical trial institution for each project is a prerequisite to qualify investigators.The SOP for training on the basis of GCP as well as practical experiences in this paper include establishing training plan, training programs for each position, pre-trail training programs, principles and techniques in training, evaluating training programs, reviewing qualifications of trainers, and maintaining training documentation and archives.

Introduction to Chinese traditional medicine database intelligent inquiry and subject selecting system

LIU Lei, TIAN Long, SHEN Jun, YUAN Bing-Xiang

2004, 9(4):  477-480. 

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The Chinese traditional medicine database intelligent inquiry and subject selecting system manages 4 databases of information on disease, herbs, their pharmacological effects and compound prescription intelligently and relatively.When a key word is input into the system, the associated information of herbs, their compound prescription, action and effects can be displayed immediately.The compound prescription can be quantitatively estimated as monarch, minister, assistant and guide in order.Following all associated data that are collected, the effective density of herbs can be arranged from a line. The design of the system has the characteristics of pertinence, flexibility, exoteric, convenience, friendship, multi-function, which can help investigator to select subject of traditional medicine scientifically.Moreover, it can be updated and extended when required.The system can promote information and modernization of researches on Chinese traditional medicine.