Table of Content

Volume 13 Issue 8
26 August 2008

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Discussion on dose and dosage regimen exploring and confirming in new drug clinical trials

YANG Jin-bo

2008, 13(8):  841-846. 

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It is generally concerned by industries that some important questions in new drug clinical trials from designing the first dose in human to confirm the last dosage regimen, which is also one of the key bottlenecks to restrict the promotion of new drug research and development in China.Based on some references and review experience, this article is to discuss dose and dosage regimen exploring and confirming in new drug clinical trials.

Experimental studies on hypoglycemic activity of active hepatin

ZHANG Xin-yue, LI Qin, CHEN Ai-jun, NI Ya

2008, 13(8):  847-851. 

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AIM:To observe the hypoglycemic activity of active hepatin in diabetic mouse or rat models. METHODS:The diabetic mice induced by alloxan were i.g.given active hepatin 1.0, 2.0, 4.0g/kg for 8 weeks.The body weight and fasting blood glucose were determined every 2 weeks.The type 2 diabetic SD rats induced by fed with high caloric diet and injected minidose streptozocin, were given active hepatin 0.75, 1.50, 3.00g/kg i.g.for 8 weeks, also the body weight and fasting blood glucose were determined every 2 weeks.In addition, the effect of active hepatin on glucose tolerance was investigated in alloxan-induced diabetic mice.RESULTS:Active hepatin reduced the levels of blood glucose and improved the glucose tolerance, and also decreased the blood sugar curve areas about alloxan-induced diabetic mice which were given the dosages 1.0, 2.0, 4.0g/kg of active hepatin.The blood glucose of type 2 diabetic SD rats induced by fed with high caloric diet and injected with minidose streptozocin could be decreased by 3.00g/kg of active hepatin.CONCLUSION:Active hepatin can adjust bloodsugar level and improve glucose tolerance.

Study on effects of hirsutella sinensis fermented mycelia on immunologic function in mice

GE Fei, Gui Lin, LI Wan-zhen, FAN Mei-zhen

2008, 13(8):  852-855. 

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AIM:To investigate the effects of hirsutella sinensis fermented mycelia on immunologic function in mice.METHODS:The mice were reared with hirsutella sinensis fermented mycelia at the doses of 50, 200 and 800 mg/kg for 5 days for tests of carbon clearance, serum haemolysin and delayed-type hypersensitivity (DTH)induced by 2-dinitro fluoro benzene (DNFB).RESULTS:The medium and high doses of 200 and 800 mg/kg enhanced phagocytosis by uninucleate macrophages, humoral immunity and cellular immunity of mice significantly with obvious dose dependence.CONCLUSION:These results suggest that the hirsutella sinensis fermented mycelia has substantial immunoregulation function.

Experimental study of gancyclovir combining HSV-TK gene therapy system on breast cancer

JIANG Hong, HOU Chen-rong, CHEN Kao-shan, WANG Ming-ning, ZHANG Yu, WANG Wen-qing, YANG Sheng-xi

2008, 13(8):  856-859. 

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AIM:To study the killing effect and the bystander effect of gancyclovir (GCV)combining herpes simplex virus thymidine kinase (HSV-TK)gene therapy system on human breast cancer cells.METHODS: GINaTK retroviral vector containing HSV-TK gene was transduced into PA317 packaging cell by liposome transfection method.The human breast cancer cell line was infected by high titer viral supernatant. MA782/5S-8102/TK cells and MA782/5S-8102 cells were used in in vitro and in vivo study.RESULTS: Experimental results revealed that in in vitro study when the cell population ratio of MA782/5S-8102/TK cells reached 10%the tumor cell-killing proportion was almost 50%, in in vivo study GCV could suppress tumor formation of the MA782/5S-8102/TK cells.After treated with GCV, the median tumor volume of mice implanted with MA782/5S-8102/TK +MA782/5S-8102(1∶9)group MA782/5S-8102/TK +MA782/5S-8102(1∶1)and MA782/5S-8102/TK cellswas respectively decreased by 11.1% (P<0.01), 30.6% and 47.2% compared with the control tumors.Tumors treated with GCV revealed different histopathological features compared with the control tumors.CONCLUSION:The HSV-TK gene could be transducted into human breast cancer line under the mediation of retrovirus and be stable expressed, HSV-TK GCV gene therapy system could improve the antitumoral efficiency.The bystander effect could be observated in HSVTK GCV system in in vitro and in vivo.

Research on anti-tumor activity of evodiamine in vitro

SONG Yu, SONG Ying, KANG Zhi-chen, ZHAO Wen-jie, LIU Xiao-xi, DENG Xu-ming

2008, 13(8):  860-864. 

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AIM:To detect the inhibition of evodiamine on ten human tumor lines and study its anti-tumor mechanism.METHODS:The inhibition of cell growth of evodiamine was measured by MTT assay. Morphological changes were observed by optical and electron microscopy.Apoptosis and cell cycle distribution of SPC-A 1 cells were determined by flow cytometry.RESULTS:Evodiamine had the selective inhibition on the growth of ten tumor lines.SPC-A 1 cells treated with evodiamine showed typical characteristics of apoptosis, the cells became round and smaller, cell detachment, membrane blebbing, cell shrinkage with a condensed cytoplasm, and vesicle formation (abundant vacuoles with multivesicular bodies).In the presence of 0.5 μg/mL evodiamine, a net increase in the percentage of cells at G₂/M phase was encountered, and this phase was maintained throughout the treatment time.CONCLUSION:Evodiamine has the selective inhibition on the growth of tumor lines and can induce morphological changes, and G₂/M arrest of SPC-A 1 cells.It is probably related to inducing cell apoptosis and cycle arrest of the tumor.

Expression of MMP-9 and TIMP-2 of carotid arterial media in spontaneously hypertensive rats and the intervention study of telmisartan

CHEN Hong, LIU Yong-ping, MA Jian-fang, ZHANG Du-sheng, JIANG Qiong

2008, 13(8):  865-869. 

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AIM:To investigate the expression and the effects of telmisartan on the matrix metalloproteinase-9(MMP-9)and the tissue inhibitor of metalloproteinase-2(TIMP-2)of carotid arterial media in spontaneously hypertensive rats(SHRs).METHODS:12 week-old male SHRs were randomized to untreated SHR group (SHR), telmisartan high dose group (TelH)and telmisartan low dose group(TelL)(n=10 for each).Age and sex matched Wistar Kyoto rats (WKY)were served as control group (n=10).After 18 weeks intervention, systolic blood pressure (SBP)of rats and area of collagen fiber percentage were measured.MMP-9 and TIMP-2 expression levels in the carotid arterial media were evaluated with immunohistochemistry staining.RESULTS:After 2 weeks, the SBP level in TelH group was significantly decreased compared to SHR group (P<0.01).And the SBP lowering effect in TelH group was kept during the experiment.However, there was no significant difference between SHR group and TelL group(P>0.05).The area of collagen percentage in carotid arterial media of SHR group were higher than that in WKY group(P<0.01).In TelH and TelL group the areas were lower than that in SHR group respectively (P<0.05 for each).The integrated optical density(OD of MMP-9 in the carotid arterial media in SHR group was markedly lower than that in WKY group(P<0.01).The OD in TelH and TelL group was higher than that of SHR group respectively (P<0.05 for each).The OD of TIMP-2 in the carotid arterial media in SHR group was markedly higher than that in WKY group(P<0.01). In TelH and TelL group it was markedly lower than that of SHR group respectively(P<0.05 for each).CONCLUSION:MMP-9 expression level decreased but TIMP-2 level increased in carotid arterial media of SHRs.Telmisartan could attenuate carotid arteries fibrosis through decreasing SBP, upregulating MMP-9 and downregulating TIMP-2 expression levels on carotid arteries of SHRs.

Expression levels of matrix metalloproteinase-9 in blood polymorphonuclear leucocyte and serum TIMP-1 and the effect of dexamethasone on them in rat asthma models

ZHOU Hua-fei, WANG Xing-xing, TONG Xia-sheng, LI Shao-bo, WANG En-zhi, RUAN Zheng-ying, YI Hui, JING Xiao-hong, GUO Hai-yuan

2008, 13(8):  870-873. 

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AIM:To investigate the expression of matrix metalloproteinase-9(MMP-9)in blood polymorphonuclear leukocyte(PMN)and the effect of dexamethasone on them in rat asthma models.To explore the relationship between MMP-9 in PMN and its inhibitor matrix metallo-proteinase inhibitor-1(TIMP-1). METHODS:The rat models of asthma were randomly divided into asthma group (group A), control group (group C)and dexamethasone treated group (group C).Blood PMN was isolated and purified.The expression of MMP-9was detected by immunocytochemical method in blood PMN.The concentration of TIMP-1protein was detected by ELISA.RESULTS:The levels of MMP-9 in PMN in group A (OD=0.196± 0.011)and in group D(OD=0.135±0.008)were significantly higher than those in group C(OD=0.100±0.010)(P<0.01).The levels of MMP-9 in PMN in group D were significantly lower than those in group A.The levels of TIMP-1protein in group A[(34.96± 4.54)ng/mL] were significantly higher than those in group C [(26.14±3.43)ng/mL] and in group D [(29.89±3.43)ng/mL] (P<0.01).The levels of TIMP-1protein in group D were significantly higher than those in group C(P<0.05).There was significant positive correlation between bloodMMP-9 in PMN protein expression level and concentration of TIMP-1protein(n=29, r=0.741, P<0.01).CONCLUSION:MMP-9 protein can be synthesized by PMN, and expression levels of MMP-9 are increased in rat asthma.PMN are involved in asthmatic inflammation and maybe by increasing synthesis of MMP-9.But this function of PMN can be inhibited by dexamethasone. MMP-9 and its inhibitor TIMP-1may take part in the pathogenesis of asthma exacerbation.

Effects of urokinase plasminogen activator on metastasis inhibition of gastric cancer cells induced by Parthenolide

ZHAO Li-jie, LI Yan

2008, 13(8):  874-879. 

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AIM:To investigate the effect of urokinase plasminogen activator (uPA)on metastasis inhibition of gastric cancer SGC7901 cells induced by parthenolide.METHODS:The changes of SGC7901 cells reproductive activity were analyzed by MTT.Light microscope was used to observe the cell morphological changes.The effects of parthenolide on migration and invasion capacity of SGC7901 cells were determined by using matrigel and transwell system.The expression of uPA was detected by Western blot and RT-PCR assays. RESULTS:Parthenolide inhibited the proliferation of SGC7901 cells in a time-and concentration -dependent manner ranging from 100 to 200 μmol/L.Light microscopy showed the suppressing effect on growth of SGC7901 cells.After exposed to parthenolide, the migration and invasion capacity of SGC7901 cells were significantly decreased, the number of cells gradually decreased through the basement membrance.The Western blot assay showed that the expression of uPA protein declined gradually after exposed to parthenolide for various period of time.CONCLUSION:Parthenolide can inhibit the growth and metastasis activity of SGC7901 cells, and uPA played an important role in the latter process.

Endoxin mediating myocardial ischemia reperfusion injury by effecting expression of apoptosis and inflammation genes

ZHENG Jian-fa, KE Yong-sheng, GAO Wen-jun, WANG He-gui

2008, 13(8):  880-885. 

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AIM:To observe the changes of cardiac muscle apoptosis and inf lammation related gene expression in rats with myocardial ischemia reperfusion (MIR)injury utilizing signal transduction gene array, and the effects on the rats after injecting antidigoxin, endoxin specificness antagon.It was testified that endoxin can mediate MIR injury by influencing apoptosis and inflammation related gene, and the mechanism of action of endoxin mediating MIR injury was consummated.METHODS:Myocardial ischemia reperfusion models were obtained by ligating left anterior descending coronary artery 30 minutes, followed by 60 minutes reperfusion.SD rats were randomly divided into three groups each with three rats :sham operation group,MIR group and antidigoxin antiserum group.After reperfusion, left ventricular myocardium samples of ischemia area were immediately processed, and the expression of related apoptosis and inflammation genes were measured with gene array technology.RESULTS:Compared with sham operation group, the apoptosis related gene expression of Bax, Bcl-2, Bcl-2L1 and Birc1b in MIR group were down regulated, but the ratio of Bcl-2/Bax was descended.The mediated inflammation related gene expression of IL, TNF, ICAM-1 were up-regulated or had the tendency of up-regulation.Compared with MIR group, the apoptosis related gene expression of Bax, Bcl-2, Birc3 in antidigoxin antiserum group were up-regulation, but the ratio of Bcl-2/Bax was upgraded.The mediated inflammation related gene expression of IL, TNF, ICAM-1 were down regulated or had the tendency of down regulation.CONCLUSION:Endoxin can down regulate the inhibition apoptosis gene expression and up-regulate inflammation gene expression.Antagonist of endoxin, antidigoxin antiserum can rivalry endoxin.It has myocardial preservation protection by down regulating the related gene of myocardium apoptosis expression and up-regulating inflammation related gene expression.

Changes of electrocardiogram induced by neurotoxin soman and rescue of benthiactzine in dogs

ZHANG Jin-jin, LONG Chao-liang, TANG Yuan, WANG Ru-huan, SONG Li-xue, WANG Hai, XIA Yun-feng

2008, 13(8):  886-890. 

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AIM:To investigate the changes of electrocardiogram(ECG), LDH and CK-MB caused by soman, and the therapeutic effects of benthiactzine. METHODS:7 healthy male dogs, weighing 12-15 kg, were given intramuscularly 1/3LD soman (1LD= 10 μg/kg)per ten minutes.The mean blood pressure lower than 40-45 mm Hg was defined as circulatory failure.The changes of ECG, heart rate, blood pressure, LDH and CK-MB were recorded either before and after soma was given or after benthiactzine was given. RESULTS:It was observed that decreased heart rate, A-V block, high and sharp T wave with or without P wave in ECG of dogs after soma was given.Meanwhile, the levels of CK-MB and LDH were increased significantly (P<0.05).The treatment of benthiactzine made the ECG recovery normal, but CK-MB and LDH did not obviously change.CONCLUSION:The cholinesterase inhibitor soman leads to serious arrhythmia which can be remedied by benthiactzine.

Effect of Dihydroarteannuin on transplantation tumor growth in C57BL/6J mice with lewis lung cancer

JIANG Yong-xin, WANG Qian, CHEN Xiao-qun, JIN Cong-guo, LI Jia, DENG Jing

2008, 13(8):  891-894. 

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AIM:To explore the anti-tumor effect and the mechanism of dihydroarteannuin in C57BL/6J mice with lewis lung cancer.METHODS:Fifty C57BL/6J mice subcutaneously planted with 3LL lung cancer cells (2×10⁶)were randomly divided into 5 groups :blank control group, same volume of normal saline group, positive control DDP group, low, middle and high dose dihydroarteannuin groups.Changes of body weight and inhibitory rate of tumor in each group were observed.The cell cycle and apoptosis rates were analyzed by flow cytometry.RESULTS:The body weights were decreased in middle and high dose group compared with NS group and the inhibitory rate of tumor were 53.50% and 59.24% respectively.FCM assay indicated that Dihydroarteannuin could induce apoptosis of lung cancer cell.At the same time, the number of G0G1 and G₂/M phase cells was decreased. Most of the cells were arrested in S1phase.CONCLUSION:Dihydroarteannuin has obviously effect on anti-tumor in C57BL/6J mice with lung cancer.Its possible mechanism might be involved in inducing cancer cell apoptosis.

Study on the signal pathway of cell apoptosis in HT-29 cells and the gene expression of AQP3 induced by sodium butyrate

ZHU Jing, HONG Hua-rong, LIU Xiao-qun, ZHOU Xiao-li, CHEN Jian-li

2008, 13(8):  895-899. 

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AIM:To investigate the signal pathway of cell apoptosis inHT-29 cells and the gene expression of AQP3 induced by sodium butyrate.METHODS: MTT method was used to detect the inhibitive effect of cell growth induced by different concentrations of sodium butyrate, while RT-PCR to detect the gene expressions of Cyclin D1, CDK4, p16 and AQP3, FCM for cell cycle detection.RESULTS:With the concentration of sodium butyrate more than 2.5 mmol/L, the cell growth of HT-29 cells was inhibited, the expressions of Cyclin D1, CDK4 and AQP3 were down-regulated while the expression of p16was up-regulated, cells were arrested in G₁/S.CONCLUSION:The apoptosis of HT-29 cells may be induced by sodium butyrate with concentrations more than 2.5 mmol/L, while the cell cycle arrested in G₁/S dose-dependently.The signal pathway of cell apoptosis may be the p16-Cyclin D1/CDK4 way, together with the down-regulation of AQP3.

Protective effects and mechanism of astragalus injection on asthmatic rats

HUANG Cui-ping, YANG He-ping, YANG Ying-qiao

2008, 13(8):  900-904. 

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AIM:To explore the protective effects and mechanism of astragalus injection on asthmatic rats.METHODS:OVA was injected intraperitoneally and inhaled to produce the asthmatic rat models.Forty rats were randomly divided into five groups :control group, asthma group and astragalus groups of high, medium and low dose.The concentration of IL-5 in BALF and the expression of IL-5 mRNA, phospho-p38 MAPK in lung tissue were respectively measured by ELISA, in situ hybridization staining and Western blot.The number of inflammatory cell in BALF was calculated and histopathology changes were observed. RESULTS:The number of inflammatory cell and the concentration of IL-5 in BALF and the expression of IL-5 mRNA, phospho-p38 MAPK in lung tissue were higher in asthmatic rat group than those in normal control(P<0.01);and those in astragalus rat group were lower than in asthmatic rat group(P<0.01).The histopathology damage was alleviated in astragalus rat group.The efficacies in the astragalus groups of high, medium and low dose were similar, showing no insignificant difference among them.The expression of phospho-p38 MAPK has positive correlation with the number of eosinophil and the concentration of IL-5, the 中国临床药理学与治疗学 2008 Aug;13(8)· 903· expression of IL-5 mRNA(r=0.62, 0.69, 0.74, P<0.01).CONCLUSION:p38 MAPK may play a role in pathological process of asthma.Astragalus could effectively treat asthma by inhibiting the expression of phospho-p38 MAPK and IL-5, and decreasing the number of inflammatory cells

Determination of the ED₅₀ of spinal anesthesia 0.75% ropivacaine for cesarean section

SHEN Xiao-shu, GAN Guo, YUAN Li-yong

2008, 13(8):  905-908. 

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AIM:To determine the median effective dose (ED₅₀)of spinal anesthesia 0.75% ropivacaine for cesarean section.METHODS:Thirty-two ASA Ⅰ-Ⅱ parturients undergoing elective cesarean section delivery with use of combined spinal-epidural anesthesia were enrolled in this study.The initial dose of was 12.8 Mg of 0.75%ropivacaine, and the dosing intervals were 98.4% of the preceding dosage.Doses for subsequent parturients were determined by the response of the previous parturient.Successful anesthesia was defined as a loss of sensation to an acupuncture stimulus at the T₇ level, full motor blockade within 10 minutes after administration of the local anesthetic, analgesia of incision and the satisfaction of skelaxin evaluated by one operator.ED₅₀ and its 95% confidence interval (CI)was determined with use of Dixon method.RESULTS:Five parturients were rejected out the study because of doubtful anesthsia.According to the rest twenty-seven parturients'data, the ED₅₀ of intrathecal 0.75% ropivacaine was 11.97mg (95% confidence interval [CI], 11.75-12.19 mg).CONCLUSION:The ED₅₀ of spinal 0.75% ropivacaine for cesarean delivery under the conditions of this study were 11.97mg.

Effects of polymorphisms of aldehyde dehydrogenase 2 gene on pharmacokinetic characteristics of isosorbide-5-mononitrate extended action tablet in Chinese healthy subjects

DU Shu-xian, LIU Yu-qing, TIAN Lei, LIU Hong, XIE Shuang, JlANG Juan-juan, WANG Ping, HUA Cong-xiao, LI Yi-shi

2008, 13(8):  909-912. 

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AIM:To investigate the effects of polymorphisms of aldehyde dehydrogenase 2 gene(ALDH2)at positions Glu504Lys on pharmacokinetic(PK)characteristics of isosorbide-5-mononitrate (IS-5-MN)in Chinese healthy volunteers.METHODS:Among 45 persons, twenty-two healthy male volunteers were selected and orally taken 60 mg IS-5-MN.An HPLC-MS method was applied to analyze IS-5-MN plasma concentration.ALDH2 genotype was determined by PCRRFLP.Pharmacokinetic analysis was performed to assess the effects of the genotype on IS-5-MN pharmacokinetics.RESULTS:In these 22 volunteers, 13 homozygous Gg and 9 heterozygous GA genotypes for ALDH2 at positions of Glu504Lys were detected by PCRRFLP.IS-5-MN plasma concentration, AUC_0-t, Cmax and t_max did not show significant statistical difference (P>0.05)in the two groups.CONCLUSION:The polymorphisms of ALDH2 gene at positions of Glu504Lys could not influence the pharmacokinetics of IS-5-MN in the research.

Open study of citalopram combined with doxepin in treating generalized anxiety disorder

TONG Jian-ming, LIU Cheng-wen, YANG Zheng-chun

2008, 13(8):  913-917. 

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AIM:To explore the clinical efficacy and safety of citalopram combined with doxepin in the treatment of generalized anxiety disorder (GAD). METHODS:The combination group was treated with citalopram (20 mg/d)and doxepin(75-125 mg/d), as the same period the other group was treated with venlafaxine, then the scores before and after 1, 2, 4, 6 weeks treatment were assessed by Hamilton Anxiety Scale (HAMA), the clinical efficacy after 6 weeks treatment using baseline reducing rate was assessed, and the adverse reaction incidence was assessed by using the TESS.RESULTS:After 6 weeks, 50 patients completed the treatment in combination group, and 30 patients completed the treatment in venlafaxine group. The expulsion rates were 10.7% and 9.1% respectively, P=0.70.The baseline reducing rate did not show any significant difference, the efficient rates were 92.0% and 93.3%, P=0.83.The effect of two methods had no significant difference through the Ridit value comparison.The psychosis anxiety factors showed conspicuous and most conspicuous difference during 4-6 weeks through HAM.The target symptoms factors were analyzed, the symptoms of insomnia, dysmnesia attention dysfunction and respiratory system of combination group were much improved(P<0.05 or 0.01)compared with the venlafaxine group.The adverse reaction was analyzed by SS collection, it showed the patients in combination group had more dry mouths, constipation and weight gain.CONCLUSION:Citalopra combined with doxepin showed the same clinical efficacy as the SNRIs and more safety, during the treatment of GAD, the treating cost would be less than 13 of the venlafaxine.It was a more practical way in treatment for the patients with lower income.

Mitochondrial DNA mutation determination for guiding aminoglycosides antibiotics individual application in a maternal inherited deafness family

LIN Wen-jin, GUO Sun-ming, ZHANG Ya-min, XU Rong-qing

2008, 13(8):  918-921. 

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AIM:To determine a mitochondrial DNA mutation in a maternal inherited deafness family, and guide aminoglycosides antibiotics individual application in other family members.METHODS:PCR-re-striction fragment length polymorphism analysis and DNA sequencing were conducted in a maternal inherited deafness patient with a definite aminoglycosides antibiotics application history.RESULTS:The patient was confirmed with a 1555 A →G mutation in mitochondrial DNA.CONCLUSION:It suggested mitochondrial DNA point mutation is one of the main reasons of deafness, the patient's sib should be cautious to use aminoglycosides antibiotics, and her progeny should be prohibited to use aminoglycosides antibiotics.

Clinical application of lidocaine carbonation on cesarean section in plateau area

CHEN Xiao-guang, LV Hong-da, SHANG An-yun, GUO Bao-chen

2008, 13(8):  922-925. 

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AIM:To compare the effect and safety of different epidural anesthesia methods on cesarean section in plateau area.METHODS:Sixty ASA I-IIpatients undergone cesarean section were randomly allocated into three groups :lidocaine hydrochloride group (group Ⅰ, epidural anesthesia with 2% lidocaine hydrochloride), lidocaine carbonation group(group Ⅱ, epidural anesthesia with 1.73% lidocaine carbonation), and bupivacaine group(group Ⅲ, spinal anesthesia with 0.5% hyperbaric bupivacaine).The anaesthesia onset time, consummate time, highest plane, and fetal disengagement time of three groups were compared.The blood pressure, heart rate, adverse reaction of patients in each group were recorded.RESULTS: Compared with group Ⅰ, group Ⅱhad faster anaesthesia onset time, shorter consummate time and fetal disengagement time.Compared with group III, group Ⅱ had less adverse reaction and less effect on blood pressure and heart rate of patients, there were significant difference.CONCLUSION:Epidural anesthesia with lidocaine carbonation on cesarean section in plateau hypoxia circumstances has the characteristics of faster anaesthesia onset time, shorter anaesthesia consummate time and exact effect, and moreover, it has less effect of haemodynamics and adverse reaction and it can elevate safety in parturient and neonate operation.Therefore, it is a safe and reliable anaesthesia method for cesarean section in plateau area.

Clinical investigation of hearing impairment in cytomegalovirus hepatitis and the curative effect of ganciclovir

XU Zhi-wei, WANG Hong-jiao, CHEN Jun-ya, CHEN Yi-ping

2008, 13(8):  926-929. 

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AIM:To analyze the hearing impairment rate of cytomegalovirus (CMV)hepatitis and explore the curative effect of ganciclovir.METHODS: 103 cases of CMV hepatitis patients were randomly divided into treatment group (65 cases)and control group (38 cases).Treatment group used Ganciclovir, supplemented symptomatic treatment, the control group used only symptomatic treatment.The blood, biochemical routine, levels of blood CMV-pp65and urine CMVDNA were determined regularly, and the brain stem auditory evoked potential (ABR)was detected.RESULTS: The positive rate of CMV-pp65, CMV-DNA of patients before and after treatment in treatment group had significant difference (P<0.01);The changes of positive rate of CMV-pp65and urine CMV-DNA before and after treatment in control group had no significant difference (P>0.05).The ABR of 103 cases of CMV hepatitis patients was tested before treatment, 27 ears were hearing impairment (13.1%).There were 17 ears hearing impairment (13.08%)in treatment group 65 cases patients, and 10ears hearing impairment (13.16%)in control group 38 cases patients, after one yearwith ganciclovir treatment, 15 ears were hearing impairment (11.54%)in treatment group and 17 ears were hearing impairment (22.37%)in control group.Compared with the two groups, the rate of hearing impairment had significant difference (P<0.05). CONCLUSION:There are the hearing impairment in part of children with CMV hepatitis, after Ganciclovir treatment the blood CMV-pp65and urine CMV-DNA in patients were negative and the incidence of hearing impairment was decreased.

Comparison of 2-week regimen and 3-week regimen based on oxaliplatin plus 5-fluorouracil and Calcium folinate as the first-line in the reatment of metastatic colorectal cancer

ZHAO Wen-ying, JI Zhao-ning

2008, 13(8):  930-933. 

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AIM:To compare the efficacy and adverse reaction of oxaliplatin (L-OHP)in first-line chemotherapy of metastatic colorectal cancer(MCC)combined with infusional 5-fluorouracil (5-FU)and Calcium folinate (CF)administered every 2 weeks (FOLFOX4regimen)or every 3 weeks.METHODS:66previously untreated MCC patients were randomized in two chemotherapy regimen group :grouop A, oxaliplatin 85 mg/m² on first day, CF 200 mg/m² infusion 2h followed by bolus 5-FU 400 mg/m² and a 22h infusion of 5-FU 600 mg/m², repeated for 2consecutive days every 2 weeks.group B, oxaliplatin 130 mg/m² on first day, CF 200 mg/m² infusion 2h followed by a 4-6h infusion of 5-FU 375-425 mg/m², repeated for 5 consecutive days every 3 weeks.RESULTS:The two regimens have similar efficacy, the response rate of group A and B was 42.9% and 38.7% respectively (P>0.05).The adverse reaction rates of the two regimen were no statistical difference.CONCLUSION:The 2-week regimen and the 3-week regimen of L-OHP combined with 5-FU/CF have the same efficacy inMCC patients.

Effects of lornoxicam on patient controlled analgesia in patients after open heart surgery

SUN Li-xin, HOU Nian-guo, AI Deng-bin, WANG Ming-shan

2008, 13(8):  934-937. 

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AIM:To observe the effects of lornoxicam on patient controlled analgesia in patients after open heart surgery.METHODS:Thirty patients were randomly allocated to lornoxicam group (n=15)and morphine group (n=15).Both groups received PCA (patient controlled analgesia)with morphine (1mg/mL).The PCA parameters were morphine loading dose of 1mg, continuous infusion dose of 0.5 mg/h, single dose of 1mg, lockout time of 10 min, and 4hours limit of 20 mg.Lornoxicam group received intravenous lornoxicam of 8 Mg while the PCA pump beginning, 12, 24 and 48h after the first dose.Morphine group received intravenous normal saline at the same four points.The following indexes were recorded at 12, 24, 36 and 48h after the PCA pumps were used :VAS scores of pain, effective pressing numbers, drug dosage, sedation degree, side effects, and patient satisfaction.RESULTS:There were no significant difference in VAS scores of pain at 12, 24, 36 and 48hours after the PCA pumps were used(P>0.05).The VAS scores of pain, effective pressing numbers and drug dose in lornoxicam group were obviously lower than those in morphine group (P<0.05).The incidence rate of nausea in lornoxicam group was obviously lower than that in morphine group (P<0.05), and there were no significant difference of the other side effects (P>0.05).There were no significant difference in patient satisfaction degree, residence time in ICU and length of stay after operation(P>0.05).CONCLUSION:Lornoxicam can relief pain in patients after open heart surgery safely and efficiently, and reduce the morphine consumption.

An effective observation of salmon calcitonin on patients with renal osteodystrophy and secondary hyperparathyroidism

LIANG Yu-huan, GAO Xin, QIAO Jing

2008, 13(8):  938-941. 

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AIM:To study the effect of salmon calcitonin (Miacalcic)in treatment of renal osteodystrophy and secondary hyperparathyroidism in patients undergoing long-term hemodialysis (HD) or hemodiafiltration (HDF).METHODS:A total of 65 patients with renal osteodystrophy and secondary hyperparathyroidism were randomly assigned to receive either Miacalcic or calcitriol.All patients were treated with HD or HDF.The visual analog scale management of pain (VAS)and levels of serum calcium and phosphorus, parathyroid hormone (PTH)were monitored during 0, 4, 8, 12 weeks of treatment.RESULTS:33 and 32 patients were randomly assigned to Miacalcic group and control group.In Miacalcic group, the levels of serum calcium, phosphorus and PTH were more effectively decreased than those of control group.At the same time, the symptoms of renal osteodystrophy, such as bone pain and joint dysfunction were more significantly improved than those of control group.There were significant difference between Miacalcic group and control group(P<0.05).But there were no contribution to occurrenced metastatic calcification.CONCLUSION:In treatment of renal osteodystrophy and secondary hyperparathyroidism, Miacalcic can alleviate bone pain symptom and reduce the high PTH, high serum phosphorus and high serum calcium effectively, is remarkably efficacious and worthiness of advanced exploration.

Research advance on the characteristics and application of CYP450 metabolic enzymes

LI Xiao-yu, LIU Gao-lin

2008, 13(8):  942-946. 

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Cytochrome P450 is an important kind of enzymes for the metabolism of drug and other endoor xeno-biotics.Classification of metabolic enzymes, molecular biological characteristic of CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, CYP1A2 and CYP2A6were described in this review.Influence of traditional Chinese medicine (TCM)on metabolic enzyme and its application in clinical drug therapeutics and drug development were also reviewed in this article.

Endoplasmic reticulum stress and atherosclerosis

FANG Xi, XUE Dan-ting, FANG Li, ZHANG Lu-yong

2008, 13(8):  947-951. 

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Endoplasmic reticulum stress has drawn much attention recently because of its potential roles in the pathomechanism of atherosclerosis.This review focused on the role of endoplasmic reticulum stress played in the initiation and development of atherosclerosis involving inflammation production, lipid metabolism dysfunction and cell apoptosis.Further more, some independent risk factors, such as hyperhomocysteinemia and hyperglycemia also induce the atherosclerosis via endoplasmic reticulum stress.

Research progress of chitosan derivatives in antitumor studies

WANG Xiao-ji, YANG Jing-ya, LIU Jian-wen

2008, 13(8):  952-956. 

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Application of chitosan derivatives in antitumor studies had gained great progress with the development of theory and practice, which exhibited good prospect for its favourable properties, such as stability, biocompatibility, biodegradability, low toxicity and long-term retention in the body.Antitumor properties of chitosan derivatives, application of chitosan derivatives as drug carrier and auxiliary function of physical therapy were concluded in this review.The data showed that chitosan derivatives played an active role in suppression of tumour growth and prolongation of survival period.

Progress of etiology and animal model in cholecystitis

KAN Hong-wei, Wei An-xiang

2008, 13(8):  957-960. 

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The animal models play irreplaceable and vital role in studying the etiology of cholecystitis, exploring its pathogeny and evaluating its treatment measures.The etiopathogenisis of cholecystitis is associated with many factors such as infection, hormone, nerve, metabolism etc.Following simulation clinical bacterium infection models, the application of common duct ligation, vagus nerve excision, food feeding, foreign matter implantation, drug inducing, and stenosis stone formation help to establish a lot of animal models which can simulate the corresponding cholecystitis.All of these models are helpful to evaluate the preclinical pharmacodynamics and further study on the mechanism and treatment measures of cholecystitis.