Table of Content

Volume 18 Issue 9
26 September 2013

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Phase II metabolism characteristics of Mycophenolic acid in the human liver tumor cells

GU Rong-rong, JIANG Chao, ZHANG feng, LIU Fu-kun, XIAO Wen-jing, CAO Bei, SHI Jian, GE Chun, A Ji-ye, WANG Guang-Ji

2013, 18(9):  961-968. 

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AIM: To assess the differences in the II phase combination capacity of the tumor cell lines and normal cell lines, we study the metabolic capacity of HepG₂ and L-O2 as for mycophenolic acid, as well as the expression of UGT1A9 in two cell lines.METHODS: Tumor cells were treated with 2.5 mmol/L and 1 mmol/L mycophenolic acid (UGT1A9 substrate) with normal cells of the corresponding organ as the control group. HPLC was used to determine the levels of drug and the glucuronidation metabolite intracellular and extracellular. Microsomal incubation of mycophenolic acid with clinically obtained human hepatic carcinoma tissue and adjacent tissues was also performed.RESULTS: The expression of UGT1A9 in HepG₂ and human liver tumor tissue was much higher than in L-O2 and adjacent tissues with a significant difference respectively (P<0.01). However, the metabolism of mycophenolic acid in HepG₂ and human liver tumor tissue was much lower than in L-O2 and human liver paraneoplastic tissues.CONCLUSION: UGT1A9 expression and function are not consistent in HepG₂ and human hepatoma tissues, which suggesting that although UGT1A9 expression is higher in tumor cells, but with some deficiency in function. This may be associated with a lack of nutrition in tumor.

Effects of intranasal administration of meserine on AChE activity and scopolamine-induced amnesia in mice

JIANG Pan, ZHENG Zhao-xi, SHAO Bi-yun, ZHANG Qi-zhi, XIE Qiong, QIU Zhui-bai, WANG Hao

2013, 18(9):  969-975. 

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AIM: The present study was designed to assess the effects of a novel cholinesterase inhibitor Meserine on cholinesterase activity and cognitive impairment induced by scopolamine in mice.METHODS: Mouse brain homogenate, mouse plasma and recombinant human AChE (rHuAChE) were used to assess the cholinesterase inhibitory activity, selectivity and enzyme kinetics of Meserine in vitro. The AChE activity and ACh level in mice brain were measured to evaluate the in vivo effect of Meserine on brain cholinergic system. Passive avoidance testand Morris water maze test were utilized to verify the efficacy of Meserine on scopolamine-induced amnesia in mice.RESULTS: Meserine possessed good inhibitory activity against AChE and BuChE, with IC₅₀ of (65.2±3.2) nmol/L and (86.7±4.9) nmol/L, respectively. Enzyme kinetics study showed that Meserine was a noncompetitive inhibitor on rHuAChE. After intranasal administration of Meserine, the AChE inhibition and ACh level in brain changed consistently. The peak of AChE inhibition (26.9%) and ACh level (1269.0 ng/g) were reached around 15 min after administration. The results of behavior tests showed that Meserine (10 μg/kg, i.n.) could significantly reverse the cognitive impairments induced by scopolamine in mice (P<0.01 vs Scop) .CONCLUSION: Our results suggested that Meserine was a potent noncompetitive cholinesterase inhibitor. Intranasal administration of Meserine could effectively ameliorate the scopolamine-induced amnesia in mice via modulating brain cholinergic system.

Effects of Taxol on the expression and distribution of connexin 43 in cultured cardiac myocytes under hypoxia

WANG De-guo, WANG Xin, WANG An-cai, ZHU Hong-jun, SUN Xian-lin

2013, 18(9):  975-980. 

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AIM: To observe the effects of microtubule stabilizer (Taxol) on the expression and distribution of Cx43 in cultured cardiac myocytes under hypoxia and investigate its new value as an anti-arrhythmic agent.METHODS: Cultured cardiac myocytes from newborn rats were exposed to hypoxia for 120 min with or without Taxol (a kind of microtubule stabilizer) in different concentrations. The expression of Cx43, polymerized tubulin and total tubulin were determined by western blots. Cx43 expression and distribution were detected by immunofluorescence staining and observed under laser scanning confocal microscope.RESULTS: In normal myocytes, Cx43 converge at nuclear membrane and intercalated discs in clusters. After 120 min hypoxia, microtubule in cardiac myocytes was depolymerized and Cx43 protein expression was reduced. Furthermore, Cx43 distribution was disorder which showing reduced at the intercalated disc and dispersively distributed in membranes. Pretreated with Taxol, microtubular depolymerization, Cx43 reduction and redistribution were inhibited in a dose dependent manner.CONCLUSION: Microtubular depolymerization and Cx43 redistribution induced by hypoxia were protected by low dosage of Taxol.Microtubule stabilizer may be acted as a new anti-arrhythmic agent.

The anti-tumor effects and mechanism of Realgar nanoparticles on orthotopic breast cancer in mice

XI Xiao-xia, FAN Lin-lan, TIAN Yong-gang, WANG Bei, ZHANG Jing-ke, CHENG Jie, WEI Hu-lai, WU Run

2013, 18(9):  981-987. 

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AIM: To study the anti-proliferating action of realgar nanoparticles (nano-realgar) on murine orthotopic transplanted breast carcinoma (4T1) in vitro and in vivo.METHODS: The firefly luciferase gene was transferred into murine 4T1 breast cancer cells with a lentiviral vector (4T1-Luc cells). Both MTT colorimetric assay and bioluminescence (BLM) assay was used to detect the cellular cell proliferation, the morphological observation and Annexin V and propidium iodide (Annexin V/PI) double-labeling were employed to assess the cell apoptosis in vitro. The 4T1-Luc cells were orthotopically implanted into the mammary fat pad of female BALB/c mice to establish the orthotopic transplanted model of mouse breast cancer, the tumor-bearing mice were treated with 4 mg·kg^-1·d^-1 and 8 mg·kg^-1·d^-1 nano-realgar, by gavage once a day, for 20 days, respectively, the optical in vivo imaging system was used to continuously and dynamically observe the growth, and at the end of the treatment the animals were sacrificed, and the tumor tissue was removed and weighed. The tumor tissue sections were prepared and stained with HE stain for examination of karyokinesis and necrosis in tumors, and the tumor angiogenesis was observed by CD₃₄ immunocytochemistry.RESULTS: Both MTT and BLM assays showed that 1.56-50 μg/mL nano-realgar significantly inhibited the proliferation of 4T1-Luc cells (P<0.05), and the morphological observation and Annexin V/PI staining displayed the typical apoptotic characteristics in the cells. Nano-realgar significantly inhibited the growth of the mouse 4T1 orthotopic breast cancer in vivo at a time- and dose-dependent manner (P<0.05). The pathological and immunocytochemistry examination showed that after nano-realgar administration, the numbers of mitotic cells and microvessels in tumor tissue markedly reduced, and the extensive necrosis region could be observed at the center of the tumor tissue.CONCLUSION: Realgar nanoparticles significantly inhibits the proliferation of murine 4T1 breast cancer cells and induces to apoptosis in vitro, and plays the anti-tumor action on orthotopic transplanted breast cancer in mice via repressing neovascularization to impel necrosis of the tumor.

Pioglitazone improves hepatic oxidative and nitrative stress in metabolic syndrome rats

ZHANG Yan, YUAN He-ming, HAN Zhen

2013, 18(9):  988-992. 

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AIM: To investigate the possible in vivo protective effects of pioglitazone (Pio) on hepatic lesions in metabolic syndrome (MS) rats.METHODS: Normal 7-week-old SD rats were fed with a high-fat, high-salt diet plus 20% sucrose solution for 16 weeks. Pio (10 and 3 mg·kg^-1·d^-1) was orally administered in MS rats from 8 weeks to the end of this study. Systolic blood pressure (SBP) was measured monthly. Liver wet weight (LW) was recorded and liver weight/body weight (LW/BW) ratio was calculated. Levels of fasting blood glucose (FBG), alanine aminotranferease (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), fasting insulin (FIns) were determined. Insulin resistance (HOMA-IR) was calculated. Hepatic total-antioxidant capacity (T-AOC), malondialdehyde (MDA) content, inducible nitric oxide synthase (iNOS) and antioxidant enzyme activities, and protein level of nitrotyrosine (NT) were measured. In addition, pathological changes were observed with HE staining.RESULTS: Compared with MS rats, treatment with Pio decreasd the SBP, LW, LW/BW, ALT, AST, TC, TG, FIns and HOMA-IR(P<0.05). Furthermore, treatment with Pio enhanced the hepatic T-AOC and SOD activity, reduced the iNOS activity and protein level of NT(P<0.05), and obviously ameliorated hepatic pathologic lesions.CONCLUSION: Pio improves lesions of hepatic structure and function in MS rats through alleviation of oxidative and nitrative stress.

The correlation between sex difference of depressive behavior and expression of monoamine transporter and MAO-B in rats

WANG Li-jia, QIN Li-juan, LIU Dan, LIU Ren, ZHOU Qi-xin

2013, 18(9):  993-998. 

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AIM: To investigate the relationship between sex difference of CUMS-induced depressive behaviors of rats and the expressions of monoamine oxidase B (MAO-B), 5-hydroxytryptamine transporter (5-HTT) and norepinephrine transporter (NET).METHODS: 60 SD rats (30 for each male and female) were randomly divided into following groups:male control group (MCG),male model group (MMG),female control group (FCG) and female model group (FMG). Chronically unpredicted mild stress (CUMS) with solitary condition was taken to establish rat depression model. The open-field test and forced swimming test were used to evaluate the behavioral changes of experimental rats. The expressions of MAO-B and 5-HTT in hippocampus and NET in pons were determined by Western blot (WB) and Real-time fluorescent quantitative PCR, respectively.RESULTS: Significantly decreasing locomotor activity in open-field test and increasing immobility time in forced swimming test in MMG and FMG with remarkable difference between MMG and FMG were observed, compared with corresponding control groups. Expressions of obviously decreased 5-HTT and elevated MAO-B and NET also were found in both model groups with significant sex differences.CONCLUSION: Depression model is much easier to be induced in male rats than female by CUMS, which may be at least partly related to the different expressions of MAO-B, 5-HTT and NET.

Comparison of two kinds of diabetic model mice

LIU Qian, WANG Qing, ZHANG Xue-mei

2013, 18(9):  999-1003. 

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AIM: To compare the classical diabetic db/db mice and another diabetic mice which were established by high-fat diet along with STZ injection for evaluating the two diabetic mice on the diabetes characteristic and the reaction to three different kinds of hypoglycemic drug.METHODS: After weaning male BALB/c mice fed with high-fat diet for 4 weeks, streptozocin(STZ)45 mg/kg were intraperitoneal injected once a day and consecutive three days.One week after the last injection, the fasting blood glucose and glucose tolerance were measured. The STZ diabetes mice were prepared successfully as their impaired glucose tolerance accompanying with fasting glucose higher than 8.0 mmol/L. The fasting blood glucose and glucose tolerance of the 8 weeks old db/db mice were also measured.The db/db mice and the STZ diabetes mice were divided into four groups randomly, treated with rosiglitazone(12 mg/kg),glibenclamide (45 mg/kg),insulin (1 U/kg) and normal saline once a day respectively.After four weeks,biochemical indexes and hormone level related to glucose and lipid metabolism were measured from the samples of the two diabetes models.RESULTS: Compared with the BALB/c normal mice, the fasting blood glucose,total cholesterol and triglycerides in STZ model mice were significantly increased(P<0.05) as well as the glucose tolerance was badly impaired, the serum insulin and c-peptide decreased significantly (P<0.05).Compared with the C57BL mice, the fasting blood glucose,total cholesterol,triglyc erides,the serum insulin and the c-peptide lever of db/db mice were all increased significantly (P<0.05)along with the impaired glucose tolerance.In the STZ experiment mice, rosiglitazone, glibenclamide and insulin decrease the fasting blood glucose and improve impaired the glucose tolerance significantly.In the db/db mice, only rosiglitazone can decrease their fasting blood glucose and improve impaired the glucose tolerance, but there was no change after treated with common dose of glibenclamide and insulin until tripling dose of insulin.CONCLUSION: The characteristics of the STZ diabetes mice induced by high-fat diet and multiple low-dose STZ injection were higher achievement ratio, the stable and lasting diabetes characters.The STZ diabetes mice were sensitive to a variety of different hypoglycemic drugs. db/db mice show severe insulin resistance blunting with endogenous and exogenous insulin.db/db mice show only the same sensitive to rosiglitazone as that of the STZ diabetes mice.

Effect of isovolemic hemodilution on pharmacokinetics of ropivacaine for sciatic nerve block in dogs

DONG Xi-chen, HUANG Yu-guang

2013, 18(9):  1004-1007. 

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AIM: To investigate the effect of isovolemic hemodilution on pharmacokinetics of ropivacaine for sciatic nerve block in dogs.METHODS: Twelve healthy adult mongrel dogs (6 male, 6 female) weighing 13.5-15.8 kg were divided into 2 groups (n=6 each): isovolemic hemodilution group and control group.The animals were anesthetized with intramuscular 3% pentobarbital 30 mg/kg.A polyethylene catheter was surgically inserted into the sheath of sciatic nerve for nerve block with ropivacaine. Femoral artery and vein was cannulated respectively. Isovolemic hemodilution group was conducted by removing blood from femoral artery and replacing it with 6% hydroxyethyl starch(HES) until hematocrit(Hct) was reduced to 25%. Ropivacaine 10 mg/kg was injected into the sheath of sciatic nerve through the catheter at 48 hours after cannulation.Arterial blood samples (5 mL)were taken for determination of plasma ropivacaine concentration (using HPLC) before and at 10, 20, 30, 60, 90, 120, 150, 180, 240, 360 and 720 min after ropivacaine injection.The pharmacokinetic parameters were determined from concentration-time data using DAS 1.0 software package.Electrocardiogram(ECG),blood pressure(BP), heart rate(HR)and heart rate(HR)were continuously monitored before and after ropivacaine injection.RESULTS: No signs of cardiovascular or central nervous system(CNS) toxicity were observed after sciatic nerve block with ropivacaine in the two groups.The pharmacokinetic parameters of t_1/2α,C_max,AUC,AUMC were decreased in the isovolemic hemodilution group, but t_1/2β,t_max were increased.CONCLUSION: Normovolemic hemodilution leads to lower plasma ropivacaine concentrations after epidural anesthesia, probably due to an increased volume of distribution.

Study on awareness of adverse drug reactions and Safe Drug Use knowledge among three kinds of medical stuff in a certain 3A-grade hospital

YANG Xiao-jun, XIE Hai-tang, XU Wen-ke, JIAYuan-wei, ZHANG Wen

2013, 18(9):  1008-1013. 

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AIM: To study the awareness of adverse drug reactions and Safe Drug Use knowledge in doctors, nurses, and pharmacists these three kinds of medical staff, thus providing reference for the development of adverse drug reaction and the clinical Safe Drug Use monitoring in depth.METHODS: We made a survey of questionnaire on the ADR and the Safe Drug Use knowledge, in medical personnel (doctors, nurses, pharmacists) from 45 clinical departments of a large 3A-Grade hospital in Anhui south region, by online survey conducted with online pharmacy survey platform. Data from the platform were derived form excel automatically, statistical analysis was performed using SPSS 19.0 software.RESULTS: The survey platform obtained 575 valid questionnaires. The average rate of awareness of medical staff on ADR and Safe Drug Use was 83.0%, and 83.4% on processes of reporting ADR. There were good awareness rate in medical personnel (doctors, nurses, pharmacists) on the basic concept of adverse drug reactions, medication errors, no significant difference was observed (P>0.05). However, the awareness rate on judgment of ADR / ADE, medication error was different significantly (P<0.001). The level of awareness of doctors, nurse was lower than that of pharmacists. On “countermeasures for treatment emergent ADR”, “mandatory items in reporting ADR”, there were no significant difference in types of medical personnel (P>0.05), however, they were different on answers to the stated time limit for ADR report (P<0.001), The awareness pharmacists was higher than the doctors and nurses.CONCLUSION: Comprehensive analysis demonstrate the level of three types of hospital staff is good overall, on the basic knowledge on the ADR and Safe Drug Use, but there are some concepts confusion on adverse drug reactions, adverse events, medication errors as well. Medical staff should improve knowledge of ADR and Safe Drug Use by various forms of training, education. as well as the judgment of the medical staff on ADR/ADE, medication errors, the level of ADR monitoring and reporting, so as to improve the level of rationality of medicine and safety.

Clinical pharmacists' participation in acute exacerbations of COPD therapy practice

LUO Song-mei, YE Wei-hong, HUA Jun-yan

2013, 18(9):  1014-1018. 

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Clinical pharmacists take part in clinical rounds and the whole treatment for patients. The specific proposal of pharmaceutical care was made according to the information of patients. The safety and effectivity of COPD patients medication can improve significantly by the pharmaceutical care. It is the pharmaceutical care can also improve the prognosis of patients, promote pharmacy professional skills of clinical pharmacists and achieve the work value of clinical pharmacists.

A mutli-center randomized double-blind controlled trial of Shenguolaonianganmao Granules in the treatment of elderly and fragile patients with common cold(Qi-deficiency and Lung-heat Syndrome)

ZHANG Qiong, MIAO Qing, ZHANG Yan-ping, FAN Mao-rong

2013, 18(9):  1019-1024. 

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AIM: To evaluate the therapeutic effect, safty and tolerance of Shenguolaonianganmao Granules in the treatment of elderly and fragile patients suffering from common cold(Qi-deficiency and Lung-heat Syndrome).METHODS: The clinical trial was designed multicentered, double blind, randomized and parallel. A total of 240 elderly and fragile patients with common cold were randomly divided into two groups: a trial group (120 patients) were treated with Shenguolaonianganmao Granules, while a control group (120 patients) were treated with Yinqiaojiedu Granules. The therapeutic course of both groups was 3 days.RESULTS: The clinical trial include 228 patients was completed,105 in trial group and 104 in control group. The total effective rate of the trial group were 97.39%, while it of the control group were 91.15%,the comparison showed that the trial group achieved better therapeutic effect than the control group; The marked effective rate of the trial group were 80%, while it of the control group were 67.26%, the comparison showed that the trial group achieved better therapeutic effect than the control group (P<0.05). Each symptom was improved after treatment. The trial group received better effect than control group in relieving inactive talking and extremities soreness symptom(P<0.05). The trial group received better effect than control group in relieving fever, headache, sore throat, sweating, cough, fatigue, aversion of wind and coldness symptom, but there was no significant statistical difference in both groups(P>0.05). Only one patient in trial group had an adverse event(bruises of the right hand) during the treatment, but it is not caused by Shenguolaonianganmao Granules.CONCLUSION: The results show that Shenguolaonianganmao Granules has a definite effect on elderly and fragile patients with common cold (Qi-deficiency and Lung-heat Syndrome) with good safety.

Key technologies elements of clinical study of TCM new drugs on children's functional constipation

ZHONG Cheng-liang, HU Si-yuan

2013, 18(9):  1025-1030. 

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The evidence of relevant systematic reviews and randomized controlled trials was assessed and graded, combined with the clinical study practice to identify eleven key elements as a focus for the clinical study of TCM New Drugs on children's functional constipation:the primary purpose and design of the study, the inclusion and exclusion criteria of the study,the treatment,the trail procedure,the effectiveness and safety evaluation, and quality control as well. In addition, six recommendations for the design of clinical study of TCM New Drugs on Children's Functional Constipation were provided.

Bioequivalence of Tolvaptan tablets in healthy Chinese volunteers

LI Zuo-jun, YANG Guo-ping, PEI Qi, TAN Hong-yi, ZHANG Ran-ran, LIU Li, CHEN Jun, LIU Shi-kun, LI Bing

2013, 18(9):  1031-1035. 

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AIM: To evaluate the bioequivalence of Tolvaptan tablets in healthy Chinese volunteers.METHODS: A single oral doses of 30 mg Tolvaptan tablets (test and reference) were given to 24 healthy volunteers according to an open randomized crossover design. The concentrations of Tolvaptan in plasma were determined by HPLC-MS/MS. The pharmacokinetic parameters of the test and reference preparation were calculated by DAS 2.1. The bioequivalence was evaluated by two one-sided t test.RESULTS: The pharmacokinetic parameters of the test and reference preparations were as follows: C_max were (179±97) and (189±86) μg/L; t_max were (2.5±1.1) and (2.5±1.0) h;AUC_0-t were (1153±488) and (1225±528) μg·h·L^-1;AUC_0-∞ were (1161±492) and (1232±528) μg·h·L^-1;t_1/2 were (5.6±2.0) and (5.6±2.0) h. The relative bioavailability of the test preparation was (95.8±18.7)%.CONCLUSION: The tested preparation was of bioequivalence to the reference preparation.

Changes of hs-CRP, CatS level in acute coronary syndrome patients serum and clinical significance

ZHOU Bi-rong, CHEN Yue-feng, ZHOU Na, YANG Jing

2013, 18(9):  1036-1039. 

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AIM: To investigate the serum high sensitive creactive protein(hs-CRP), cathepsin S (CatS) level changes and clinical significance in acute coronary syndrome patients. METHODS: All patients were divided into acute coronary syndrome (ACS group,n=53) and control group(n=36).The levels of serum hs-CRP and CatS in two groups were detected and compared before and after treatment.RESULTS: There were no significant difference of two groups in gender, age, smoking, diabetes, cerebral infarction, hypertension prevalence rate. The levels of serum CatS and hs-CRP in ACS group before treatment and control group were (0.51±0.03) nmol/L,(10.21±5.03) mg/L and (0.43±0.04) nmol/L,(3.64±1.87) mg/L,respectively;there were statistically significant differences(P<0.05).After treatment,the levels of serum CatS and hs-CRP in ACS group were (0.45±0.06) nmol/L and (6.05±3.25) mg/L, compared with before treatment (0.51±0.03) nmol/L and (10.21±5.03) mg/L, which were significantly decreased, there were statistically significant differences(P<0.05).CONCLUSION: Changes of hs-CRP, CatS level in ACS patients suggest that hs-CRP and CatS may play an important role in acute coronary syndrome, CatS may possibly act as a new biomarker of ACS.

Effects of premedication with celecoxib and pregabalin on postoperative pain in the elderly orthopedic patients

ZHANG Chang-feng, ZHENG Xian-he, HU Shuang-yan, CHEN Nian-ping, LI Yu-hong

2013, 18(9):  1039-1043. 

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AIM: To observe the safety and effect on postoperative pain of premedication with celecoxib and pregabalin in the elderly orthopedic patients.METHODS: One hundred ASA ⅠorⅡelderly patients aged 68-84 year and weighing 52-64 kg undergoing elective operation on the femoral head or hip joint were randomly divided into 4 groups(n=30 each):control group(group C), celecoxib group(group S), pregabalin group(group P) and combination group(group L). Celecoxib 200 mg was taken in group S, pregabalin 300 mg was taken in group P, celecoxib 200 mg and pregabalin 150 mg were taken in group L before operation 1 h, while in group C placebo was taken. Patient-controlled intravenous analgesia with fentanyl and tramadol was used in all patients in 72 h after operation. If VAS score was more than 3, a bolus of fentanyl 0.2 μg/kg was given i.v.. And then the recovery time, moving VAS score and Ramsay score at 2,4,6,8,12,24 h postoperation, and total amount of fentanyl and tramadol in 72 h postoperation, and the incidence of adverse reaction included dizzy, lethargy, nausea and vomiting were recorded.RESULTS: Moving VAS score in group C at 2,4,6,8 h postoperation was higher than in other groups at the same time,while the score in group L at 8,12 h postoperation was lower.Ramsay score in group P at 2,4,6 h postoperation was higher than that in other groups at the same time,while the score in group L at 2,4 h postoperation was higher than that in group C and S. Compared with group P, the recovery time was shorter in group C, S and L.Compared with group C, the total amount of fentanyl and tramadol consumed in 72 h postoperation was smaller in group S, P and L. Compared with group L, the total amount of fentanyl and tramadol consumed was bigger in group S and P. Compared with group P, the incidence of adverse reaction was lower in group C, S and L (P<0.05).CONCLUSION: Celecoxib combined with pregabalin pretreatment can be used safely in elderly orthopedic patients, and can significantly reduce postoperative pain.

The clinical application of advanced treatment of flurbiprofen and dexmedtomidine in tonsillectomy of children

YI Sheng-hua, CHEN Zhong-hua, HU Shuang-yan, ZHONG Jun-feng, LI-Jun

2013, 18(9):  1044-1048. 

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AIM: To investigate the effects of advanced using flurbiprofen and dexmedetomidine in children undergoing tonsillectomy.METHODS: 60 children undergoing tonsillectomy were randomly divided into 3 groups, the control group (groupⅠ,n=20), flurbiprofen group(groupⅡ,n=20), flurbiprofen and dexmedetomidine group (groupⅢ,n=20). Children were received 2 mL saline, 1 mg/kg fiurbiprofen, 1 mg/kg fiurbiprofen and 0.5 μg/kg dexmedetomidine before induction in each group respectively. After intravenvous induction, all children were maintained with sevoflurane. Blood pressure and heart rate were recorded during operation. Agitation Scale (pediatric anesthesia emergence delirium,PAED) and analgesia (children and infants postoperative pain scale,CHIPPS) was assessed at extubation and after 5,10,15,30 minutes.RESULTS: Compared with groupⅠ,there were significant reduction in perioperative and postanesthetic recovery dosage of fentanyl in group Ⅲ.The occurrence of hypoxemia in PACU were 25%,20% and 5% in groupⅠ, Ⅱ and Ⅲ respectively. The occurrence of hypoxemia in group Ⅲ was significantly lower(P<0.01) and the same as incidence of postoperative nausea and vomiting (30%)(P<0.01). In comparison with groupⅠ, there were slower heart rate in postextubation 5 and 10 minutes,decreased PAED score and CHIPPS scale in time of extubation, postextubation 5 minutes,10 minutes in group Ⅲ. No difference was observed about time of eye open and extubation among three groups.CONCLUSION: Advanced use flurbiprofen and dexmedetomidine can relieve pain,provide stable hemodynamics and reduce incidence of postoperative nausea,vomiting and agitation.

Clinical observation of Lobaplatin combined with Irinotecan in the treatment of extensive-stage disease small-cell lung cancer

XIAO Xiao-guang, CHEN Yuan

2013, 18(9):  1049-1052. 

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AIM: To investigate the effects and side effects of Lobaplatin plus Irinotecan regimens in the treatment of patients suffered from extensive stage disease small-cell lung cancer (ED-SCLC).METHODS: 25 patients suffered from ED-SCLC were treated by Lobaplatin 35 mg/m² i.v.d1 plus Irinotecan 80 mg/m2 i.v.d1,8, every 3 weeks. Efficacy was estimated by imaging every 2 cycles.RESULTS: In 25 evaluable patients,CR was 4% (1/25),PR was 36% (9/25), SD was 28%(7/25), and PD was 32% (8/25). The objective response rate(ORR)was 40% . The disease control rate (DCR) was 68%. The median progression free survival (PFS) was 5.3 months. The median overall survival(OS) was 7.6 months. The most commonly seen adverse events(AEs) were myelosuppression and diarrhea. There was no treatment-related death.CONCLUSION: The treatment of Lobaplatin plus Irinotecan shows an effective antitumor activity and a favorable toxicity profile in patients with ED-SCLC.

Efficacy and safety of domestic olmesartan in treatment of mild to moderate essential hypertension

LIU Weng -jie, KE Yong -sheng, YANG Hao, WEI You-quan, CAO Heng

2013, 18(9):  1053-1058. 

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AIM: To evaluate the efficacy and safety of domestic olmesartan in treatment of mild to moderate essential hypertension in comparison with Ao tan and to verify its equivalency with the original study medicine.METHODS: 57 patients with mild to moderate essential hypertension were enrolled in a randomized,double-blind, multi-center, paralleded and active-controlled trial, and were divided into olmesartan group (27 patients with domestic olmesartan 20 mg+Ao tan simulated piece 1 piece 20 mg) and Ao tan group (30 patients with Ao tan 20 mg+domestic olmesartan simulated piece 1 piece 20 mg) for a 8-week therapy. All patients were followed up every two weeks, and the efficacy and adverse effects were observed. After treatment for 2 weeks, dosages of drugs were doubled in patients with seated diastolic blood pressure≥90 mm Hg (1 mm Hg=0.133 kPa).RESULTS: Compared with those before treatment, both systolic blood pressure and diastolic blood pressure significantly decreased in domestic olmesartan group and Ao tan group 8 weeks after treatment [(22.5±9.5) mm Hg and (21.4±9.5) mmHg, respectively for systolic blood pressure (P<0.001); (16.1±5.5) mm Hg and ( 14.7±4.4) mm Hg, respectively for diastolic blood pressure (P<0.001) ], while there was no significant difference between these two groups (P>0.05). There was no significant difference in total effective rate (96.30% vs 92.60%) and incidence of adverse effect between these two groups (P>0.05) .CONCLUSION: Domestic olmesartan is very effective in treatment of mild to moderate hypertension in a daily dose of 20-40 mg with good tolerability.

The role of Wnt signaling pathway during central nervous system development and diseases

LIU Mei, LIAO Hong

2013, 18(9):  1059-1064. 

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Wnt signaling pathway that widely exists in multicellular eukaryotes and plays an essential, decisive and directional role in regulation of a variety of life processes is one highly conservative signaling pathway. Traumatic brain injury, cerebral stroke and neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) that have a high rate of fatality and disability, are still the important diseases threatening the health of human beings around the world. In recent years, Wnt signaling pathway has gradually drawn more and more attention from people for the critical role played in neural development and central nervous system (CNS) diseases. To clarify the molecular mechanisms of Wnt signaling pathway comprehensively and deeply will probably offer new ideas and methods to the prevention and treatment of CNS diseases. This article summarizes the important role in regulating cellular development and demise and the relationship of canonical Wnt/β-catenin signaling pathway with the neurological diseases.

Advances of the influence of nonalcoholic fatty liver disease on the pharmacokinetics

LI Rong-hui, HUANG Mei-ling, TAN Hong-yi, PEI Qi, XIANG Yu-xia, YANG Guo-ping

2013, 18(9):  1065-1075. 

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Nonalcoholic fatty liver disease(NAFLD) is one most common chronic liver disease,and it is a big threat against people's health.Chronic liver disease is the most important causes of effects on drug disposition,and it may lead to changes of gene,mRNA and protein expression.The results of NAFLD animal models and NAFLD patients show that drug metabolic enzymes and transporters significantly change in NAFLD. Drug metabolic enzymes and transporters play important roles in drug disposition,and lead to consequences for interindividual differences in disposition kinetics, interaction profiles of clinical drugs, susceptibility to side effects and treatment efficacy.With the prevalence of NAFLD, NAFLD patients have to take more and more drugs.So this review focuses on the influence of nonalcoholic fatty liver disease on the pharmacokinetics.

Update in the pharmacotherapy for neuropathic pain treatment

LI Zhao-sheng, LIN Hong, SHA Mo, DING Zhen-qi

2013, 18(9):  1076-1080. 

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Neuropathic pain is a form of chronic pain caused by nervous lesions and significantly reduces patients' quality of life. Nowadays pharmacotherapy is still the main therapeutic paradigm. The article summarizes the underlying molecular pharmacologic mechanisms of the drugs used in the pharmacotherapy as well as their application characteristics in the clinical practice, and points out the perspective of the development of targeted drugs on the basis of elucidating the mechanisms of neuropathic pain.