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    药物研究
  • 药物研究
    A Toxicological Study of Doxepin Hydrochloride Cream in Animals
    PAN Jingyuan;QIU Yinsheng;YAN Hanchi;LING Sha
    2006, 25(2): 0-0.
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    ObjectiveTo inspect the safeness of percutaneous application of doxepin hydrochloride cream (DHC) in animals. MethodsExperiment①: 6 rabbits were randomly divided into 2 equal groups: intact skin group and dermal injury group. 24 h before the beginning of the experiment, rabbits of both groups were subjected to localized depilation of the skin of the back to the left and right of the spine. Dermal injury was produced by scraping the skin with a sterilized needle until oozing of blood began to appear. An autocontrast method was adopted in which changes in the skin on both sides of the spine of the same animal were compared. In rabbits of both groups, the upper part of the depilated area to the left of the spine was smeared with 5%DHC while the lower part was painted with 10% DHC. The upper part of the depilated area to the right of the spine was smeared with the ground substance of the cream while the lower part was left for blank control. Skin irritation caused by the single application of DHC was kept under observation. Another 6 rabbits were divided and treated as described above except that DHC and control substances were applied once daily for 7 consecutive days. Skin irritation caused by repeated applications of DHC was kept under observation. Experiment ②:32 rabbits were randomly divided into 4 equal groups each of which was subdivided into 2 subgroups, the intact skin subgroup and the dermal injury subgroup. 24 h before the experiment, the animals were depilated and dermal injury was produced as described in experiment ①. 10 g of 10%, 20% and 30% DHC were smeared onto the depilated skin areas of each of the rabbits of the 3 groups, respectively. Equivalent amounts of ground substance were applied similarly for rabbits of the 4th group. 24 h. later, the remnants of the drug and ground substance were washed away. Acute toxic skin reactions of DHC were kept under observation for 14 consecutive days. Experiment ③: 30 guinea pigs were randomly divided into 3 equal groups. 0.2 g of 5% DHC, 0.2 g of ground substance and 0.2 mL of allergen (1% 4-DNCB in 75% ethanol) were smeared onto the depilated skin of each of the animals of the 3 groups, respectively. The test substances were washed away 6 h later. The experiment was repeated on day 7 and day 14. Skin allergic reactions caused by the drugs were kept under observation. 14 days after the last smearing of the drugs, 0.2 g of DHC was smeared onto the right depilated area of each of the guinea pigs. The test substances were washed away 6 h. later and skin allergic reactions were kept under observation immediately and 24,48 and 72 h. after the washing, respectively. 0.2 g of ground substance and 0.2 mL of 0.1%DNCB were similarly applied onto the right depilated areas of guinea pigs for control. ResultsNo irritative dermal reaction in intact or injured skin was induced by single or repeated applications of DHC. No major toxic effects were observed after the applications of 10%,20% and 30% DHC. 5 h after the smearing of 30% DHC, slight somnolence was observed in the rabbits, which faded away 12 h. afterwards. No allergic skin reactions were induced by DHC in guinea pigs. ConclusionDHC was shown to exert no apparent irritative or toxic effects on the skin of rabbits, nor allergic skin of reactions in guinea pigs.
  • 药物研究
    A Study of the Protective Effect of the Extract of Hypericum Sinense L. against DNA Injury
    YANG Yu;XIANG Guangya;RUAN Jinlan
    2006, 25(2): 0-0.
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    ObjectiveTo study the protective effect of the extract of Hypericum sinense L. against DNA injuries. MethodsA cupric sulfatereaction system and a DNAinjury model system were prepared. Methanol extracts of the 3 chemical component parts of Hypericum sinense L.F002, F003 and F004 were separately added to the systems. 5 different concentrations of each of the 3 chemical component parts were used in the experiment. A chemiluminescence method was used to study the effects of the extracts of the 3 different chemical component parts on the chemiluminescence dynamic curves of the injured DNA. ResultsA striking fall and backward shifting of the peaks of the chemiluminescence dynamic curves of the injured DNA were demonstrated with the addition of the extracts of the different chemical component parts of Hypericum sinense L., and the higher the concentration of the extracts, the grater the fall of the peaks of the chemiluminescence dynamic curves of the injured DNA. The sequence of the strength of the antioxidative capability of the 3 components was shown to be F002＞F004＞F003. ConclusionHypericum sinense L. belongs to preventive and chainbreaking antioxidants. It has definite protective effects against DNA injury and the effects are related to the polarity of the chemical compounds.
    • 药物与临床
  • 药物与临床
    A Clinical Appraisal of the Effect of Subanesthetic Doses of Ketamine in Postoperative Patientcontrolled Intravenous Analgesia
    LIAO Zhipin;ZHANG yi;ZHANG Xianwei;TIAN Yuke
    2006, 25(2): 0-0.
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    ObjectiveTo survey the clinical therapeutic effectiveness of subanesthetic doses of ketamine in postoperative patientcontrolled intravenous analgesia (PCIA) .Methods80 patients of ASA grade Ⅰ－Ⅱ were subjected to midlower abdominal operations under combined endo tracheal intubation and intravenous anesthesia. Microanalgesic pump was started to work at the time when the skin was sutured before termination of the surgery. The patients were then randomly divided into 4 equal groups: K1 (ketamine group 1), K2 (ketamine group 2), F (fentanyl group) and M (morphine group). The loading doses of the patientcontrolled analgesics of the 4 groups were 0.25 mg·kg-1,0.50 mg·kg-1,1g·kg-1 and 0.15 mg·kg-1,respectively .The background infusion doses were 10 mg·h-1, 20 mg·h-1 ,10 g·h-1 and 1 mg·h-1, respectively ,while the pressing doses were 10 mg, 20 mg, 10 g and 0.5 mg , respectively ,with intervals of 5 min. Heart rate, blood pressure ,respiratory rate , pulse blood oxygen saturation ,visual analogue score(VAS),Prince Henry Score (PHS),sedation score(SS) and incidence of adverse reactions within the following 24 h were kept under observation and total doses of the drugs used in the 24 h were noted down.ResultsThe VAS and PHS in patients of group K1 were strikingly higher than those of the other 3 groups (P＜0.05). The differences between the SS in patients of the 4 groups were not significant (P＞0.05). The postoperative incidence of nausea and vomiting in patients of group M was higher than those in patients of the other 3 groups (P＜0.05). The incidences of delayed postoperative flatus passing in patients of group F and group M were higher than those in patient of group K1 and group K2 (P＜0.05).ConclusionWhen used in postoperative PCIA, proper subanesthetic doses of ketamine was shown to exert the same and satisfying effects as those of morphine or fentanyl and the incidences of nausea, vomiting and delayed flatus passing in patients treated with ketamine were lower than those in patients treated with morphine.
    • 药物研究
  • 药物研究
    Screening and Cloning of the Target Genes Transactivated by Recombinantβinterferon Protein using Suppression Subtractive Hybridization Technique
    ZHONG Yanwei;CHENG Jun;QU Jianhui;ZHANG Liying;GUO Jiang;LI Xiaodong
    2006, 25(2): 0-0.
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    ObjectiveTo clone and identify human genes transactivated by recombinant βinterferon protein. MethodsSuppression subtractive hybridization (SSH) and bioinformatics techniques were used for screening and cloning of the target genes transactivated by recombinant β-interferon protein. The mRNA was isolated from HepG2 cells induced by recombination β-interferon and 0.9 percent sodium chloride, respectively, and the SSH method was employed to analyze the differentially expressed DNA sequences between the two groups. After the restriction enzyme Rsa I digestion, small size cDNAs were obtained. Tester cDNA was then divided into two groups and linked up to the specific adaptor 1 and adaptor 2, respectively. After the tester cDNA had been hybridized twice with the driver cDNA and had undergone two times of nested PCR, the products were subcloned into T/A plasmid vectors to set up the subtractive library. Amplification of the library was carried out with transfection of E. coli strain DH5α. The cDNA was sequenced and analyzed in Genbank with Blast search after PCR.ResultsThe cDNAs differentially expressed by genes transactivated by recombinant β-interferon protein were successfully constructed. The amplified library contained 50 positive clones. Colony PCR showed that 31 clones contained 2001 000 bp inserts. Sequence analysis was performed in 31 clones randomly, and the fulllength sequences were obtained with the bioinformatics method. Altogether 20 coding sequences were obtained, including a new gene with unknown function.ConclusionThe sequences obtained may be target genes transactivated by recombinant βinterferon protein, and some of these genes coding proteins may be involved in cell cycle regulation, metabolism, and apoptosis.
  • 药物研究
    A Study of the OprD2 Gene of Pseudomonas Aeruginosa in Relation to Its Tolerance to Imipenem
    XIE Lili;XIONG Shengdao;LIU Jin;XU Shuyun;XU Yongjian
    2006, 25(2): 0-0.
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    ObjectiveTo study the genelevel mechanism underlying the imipenemresistance of pseudomonas aeruginosa(PA).MethodsA PCR method was used to detect the OprD2 gene in PA. The relationship between the mutation of OprD2 and drugtolerance of the bacteria was investigated in 12 strains of imipenemresistant and 6 strains of imipenemsensitive PA isolated in the clinic. Meanwhile, a standard strain of PA ATCC27853 was also studied. The results were analyzed with the Chisquare test. Results8 of 12 strains of imipenemtolerant PA were shown to be negative for the OprD2 gene while 4 of them were positive. In contrast, all of the 6 strains of the imipenemsensitive PA were found to be positive for the OprD2 gene, and so was the standard strain ATCC27853.The results of Chisquare test revealed that the difference between the positive rates of the OprD2 gene in the imipenemtolerant and sensitive PA was statistically highly significant. Besides, a new type of the OprD2 mutation was discovered in the drugtolerant PA. ConclusionMutation of OprD2 was shown to be an important mechanism underlying the imipenemtolerance of PA. 2 types of OprD2 mutation were found in the study, the deletion mutation and the insertion mutation.
  • 药物研究
    Effect of Aidi(AD) Injection on the Immune Function of the Mouse Bearing H22 Tumor
    TANG Lan;ZENG Fanbo;WU Minghui;LIN Jialiang
    2006, 25(2): 0-0.
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    ObjectiveTo study the anticancer activity of Aidi(AD) injection and probe into its immunoenhancing effect as well as the corresponding mechanisms. MethodsExperiment①: 50 Balb/c mice were randomly divided into 5 equal groups: control group, model group and three trial groups. Mice of the model group and trial groups were given each a hypodermic injection of 0.1 mL of H22 tumor cell suspension (containing 2×107 cells·mL-1)at the subaxillary region. Mice of the control group were given no injection. 24 hours later, mice of the three trial groups were given each an intraperitoneal injection of AD injection at lose dose (1 g·kg-1 in 0.2 mL), medium dose (2 g·kg-1 in 0.2 mL) and high dose (3 g·kg-1 in 0.2 mL), respectively. The injections were given once daily for 5 consecutive days. Mice of the control group and model group were given intraperitoneal injections of equivalent amounts of 0.9% sodium chloride solution q.d. for 5 days as well. On the 5th day of the experiment, mice of all the 5 groups were given each an intraperitoneal injection of 0.2 mL of 20% SRBC (sheep red blood cells) suspension and the afore mentioned treatment for different groups of mice was continued for another 5 days. On the 10th day, blood samples were taken from the postorbital venous plexuses of the animals. The value of absorbance at the 50% hemolytic dose (HC50) was assayed with the antihemolysin antibody method. Experiment②: 50 Balb/c mice were divided and inoculated with suspensions of H22 tumor cells in the same manner as described in Experiment ①. 24 h later, mice of the 3 trial groups were given intraperitoneal injections of AD injection at the same low dose, medium dose and high dose, respectively, as described in Experiment ①. These injections, however, lasted 11 days. Mice of the control group and model group were given intraperitoneal injections of equivalent amounts of 0.9% sodium chloride solution for 11 days as well. On the 12th day of the experiment, the body weight of each mouse was noted down and the animals were sacrificed after blood samples had been taken. The spleen index and thymus index were calculated and serum concentrations of IgG, IL-2, TNF-α determined with ELISA.ResultsThe HC50 value of the mice of the control group and three trial groups treated with AD injection were significantly higher than those of the mice of the model group（P＜0.01）. The spleen index and thymus index of the mice of the control group and three trial groups were also strikingly greater than those of the mice of the model group (P＜0.05 or P＜0.01). Besides AD injection was shown to dramatically increase the production of IgG, IL-2 and TNF-α in tumorbearing Balb/c mice.ConclusionAD injection was shown to strikingly enhance the immune function of tumorbearing mice.
  • 药物研究
    Effect of Rosiglitazone Maleate on the Expression of Tanis mRNA in the Liver Tissue of the Rat
    LIU Jie;XU Yancheng
    2006, 25(2): 0-0.
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    ObjectiveTo study the effect of rosiglitazone maleate on the expression of Tanis mRNA in the liver tissue and the plasma level of interleukin-6（IL-6）in the rat.Methods24 male Wistar rats were randomly divided into 3 equal groups: model group, trial group and control group. An insulinresistance model was set up for each rat of both model group and trial group by feeding the animals on high sugar, high fat forage for 6 consecutive weeks. Rats of the control group were fed on routine chow. In the following 2 weeks, rats of the model group and trial group were given each 4 mg·kg-1 of placebo and rosiglitazone maleate, q.d., respectively . The drugs were administered by gastrogavage. After the termination of the twoweek treatment, rats of all 3 groups were subjected to a 12 h fasting and blood samples were collected for the determination of fasting blood glucose (FBG) and fasting blood insulin (FINS). The insulinresistance index (IR) was calculated according to the Homa formula. The animals were then sacrificed and liver tissues were taken for the determination of the expression of Tanis mRNA with RT-PCR. The plasma IL-6 was determined with ELISA. ResultsThe level of plasma IL-6 was significantly higher in rats of the model group than that in rats of the control group (P＜0.05). The expression of Tanis mRNA by the liver tissue in rats of the model group was also much higher than that in rats of the control group (P＜0.05). The level of plasma IL6 and expression of hepatic Tanis mRNA were significantly lower in animals of the trial group than those of the model group （P＜0.05）. It was shown by multivariate regression analysis that plasma IL-6 levels were positively correlated with FINS and Homa-IR (r1＝0.633, P＝0.014;r2＝0.638, P＝0.015). The expression of Tanis mRNA in the liver tissue was positively correlated with plasma IL-6,FINS and Homa-IR （r1＝0.606, P＝0.022；r2＝0.651,P＝0.012；r3＝0.584, P＝0.028）. ConclusionThe high expression of Tanis mRNA in the liver tissue may be one of the mechanisms underlying insulin resistance and development of diabetes mellitus. Rosiglitazone maleate was shown to effectively mitigate insulinresistance, lower the level of IL-6 and expression of Tanis mRNA in the liver tissue in rats.
    • 药物与临床
  • 药物与临床
    Effects of Sodium Nitroprusside on the Time of Rewarming and Cardioversion during Heart Operations in Children up to Three Years of Age
    YU Qijing;CHEN Mingsen;ZHOU Qingshan
    2006, 25(2): 0-0.
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    ObjectiveTo study the effects of sodium nitroprusside on the time of rewarming and cardioversion during heart operations in children up to three years of age. Methods56 children suffering from congenital heart diseases and scheduled for corrective therapy of the deformities were randomly divided into 2 groups: the sodium nitropruside group (n＝36) and the control group (n＝20). These children up to 3 years of age had a cardiac function of Grade Ⅱ to Grade Ⅲ. Systemic rewarming was begun at the time when 2/3 of the work of operation had been completed and the nasopharyngeal temperature and rectal temperature gradually rose to 36.5－37 ℃ and 35－36 ℃, respectively. Beginning from the starting of rewarming, patients of the sodium nitroprasside group was given each sodium nitroprusside (0.2－6.5 μg·kg-1·min-1) administered continuously via the central vain with a Grasly micropump. The mean arterial blood pressure in all patients were maintained within the range of 40－50 mmHg. All of the patients were subjected to extracorporeal circulation while endotracheal intubation was used to control respiration. The patients were given each IV injections of midazolam(0.15 mg·kg-1), fentanyl(20 μg·kg-1) and pancuronium bromide(0.1 mg·kg-1) for anesthesia induction and disconnected IV injections of fentanyl(10 μg·kg-1) and pancuronium bromide (0.1 mg·kg-1) for maintenance anesthesia. Electric cardioversion was carried out of no spontaneous heartbeat took place or cardiac arrhythmias could not be converted to sinus rhythm 5 min after the declamping of the aorta. The time from the beginning to the termination of rewarming (t1) and that from declamping the aorta to the restoration of sinus rhythm (t2), as well as quantity of sodium nitroprusside used from the beginning of rewarming to the reappearance of sinus rhythm (Q) were noted down. ResultsThe value of t1 and t2 in patients of the sodium nutroprusside group were significantly smaller than those in patients of the control group (P＜0.01). The value of Q in patients of the sodium nitroprusside group was negatively correlated with t1 and t2 (P＜0.01) while the value of t1 was positively correlated with t2 in these patients (P＜0.01). ConclusionProper use of sodium nitroprusside during heart operations in young children was shown to shorten the time of rewarming and promote restoration of sinus rhythm.
    • 药物研究
  • 药物研究
    Effects of Rifampicin on the Pharmacokinetics of Isoniazid in Dogs
    FU Xiang;DENG Lidong;JIANG Xuehua;DENG Hang;LU Laichun;JIA Yuntao;LI Suhua
    2006, 25(2): 0-0.
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    ObjectiveTo study the effect of rifampicin on the pharmacokinetics of isoniazid in dogs. MethodsA twoperiod, twopreparation crossover, autocontrol design was employed for the experimental plan. 6 adult dogs were randomly divided into 2 equal groups: A and B. Dogs of group A were given each 100 mg of isoniazid at 8 a.m. and 8 p.m., respectively. Dogs of group B were given each 100 mg of isoniazid at 8 a.m., 300 mg of rifampicin and 100 mg of isonizid at 8 p.m., respectively. The drugs were administered by gastrogavage and the course of medication lasted 3 days. Dogs of group A were then given each 200 mg of isoniazid while dogs of group B were given 200 mg of isoniazid and 300 mg of rifampicin after a 12 h fasting. Blood samples were taken from the animals for the determination of the plasma concentration of isoniazid with HPLC. A ZORABX SBODS column (4.6 mm×250 mm,5 μm) served as the solid phase; the mobile phase was methanol0.02 mol·L-1 phosphate butter(pH＝6.2), column temperature was 40 ℃ and the flow rate ,1.0 mL·min-1,amount of sample added, 20 μL, ultraviolet detection wavelength, λ＝268 nm. The content of isoniazid was determined with pigrazinamide as the internal standard. After an interval of 2 weeks, dogs of the 2 groups were subjected to a crossover medication with the method described above, and the afore mentioned laboratory examinations were carried out once more. ResultsThe differences between the AUC0→24 of isoniazid in different dogs were highly significant, indicating apparent diversities of the absorption and elimination of isoniazid in different individuals. The differences between different medication periods, however, were not significant. ConclusionIt was shown that rifampicin and isoniazid had no adverse interaction and rifampicin had no evident influence on the phamacokinetics of isoniazid in dogs.
  • 药物研究
    Influence of 3 Antiviral Drugs on the Hemoglobin Concentration and Reticulocyte Count in the Peripheral Blood of the Rabbit
    WANG Jianfu;SHANG Guomei;WANG Weijin;WU Mao
    2006, 25(2): 0-0.
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    ObjectiveTo assess the effects of 3 commonly used antiviral drugs ribavirin, ganciclovir and vidarabine monophosphate on the erythropoiesis in the rabbits. Methods20 male rabbits were randomly divided into 4 equal groups A, B, C and D. Rabbits of the group A,B,C and D were given each an IV injection of 15 mg·kg-1 of ribavirin,10 mg·kg-1 of ganciclovir, 10 mg·kg-1 of vidarabine monophosphate and 2 mL of 0.9%sodium chloride solution q.d. respectively, for 14 consecutive days . Changes in the hemoglobin concentration (Hb) and reticalocyte count (Ret) of the peripheral blood were kept under observation every 4 days. ResultsThere was a striking decrease in Hb and a prominent increase in Ret that began from the 4th day of treatment in rabbits of group A and the data began to return to normal levels gradually 7 days after the discontinuation of the medication. In animals of group B, Hb showed no apparent changes while Ret was slightly increased and declined 1 week after the discontinuation of the drug. In rabbits of group C, there was a gradual decrease in Ret that rose again a bit 1 week after the discontinuation of the drug. No apparent changes in Hb and Ret were noticed in rabbits of group D. ConclusionThe 3 commonly used antiviral drugs ribavirin,ganciclovir and vidaraline monophosphate were shown to exert deleterious effects in varying degrees on hemopoiesis in the rabbit and care should be taken in the clinical application of the three drugs.
    • 药品质量控制
  • 药品质量控制
    Determination of the Content of Icariine in Qiangyangbaoshen Pills with HPLC
    ZHAO Dacheng
    2006, 25(2): 0-0.
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    ObjectiveTo set up an HPLC method for the assay of the content of icariine in qiangyangbaoshen pills. MethodsThe sample was purified with a polyamide column after 75% ethanol extraction. The quantitative analysis was performed on a C18 chromatographic column (4.6 mm×250 mm,5 μm) with a mobile phase of methanolwaterglacial acetic acid (60∶39∶1). The flow rate was 1 mL·min-1 and the detection wavelength at 270 nm according to the external standard method. ResultsGood linearity of icariine was showed when the amount of sample added was within the range of 0.058～1.153 g (r＝0.999 8), the average rate of recovery was 98.9%, and RSD was 2.3%.ConclusionThe method is handy, accurate and may be used for the quality control of qiangyangbaoshen pills.
  • 药品质量控制
    Determination of Quercetin and Rutin in Lespedeza virgata with RPHPLC
    WANG Wenqing;LUO Xiaomei;ZHANG Fei;WANG Qiulan;FANG Jianguo
    2006, 25(2): 0-0.
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    ObjectiveTo set up an RP-HPLC method for the separation and determination of quercetin and rutin in Lespedeza virgata.MethodsStationary phase: Lichrosorb C18 column (4.6 mm×150.0 mm, 5 μm); mobile phase : acetonitrile methanolwaterphosphoric acid（47∶53∶0.2）; flow rate :1 mL·min-1 ; detection wavelength: 371 nm; column temperature:40℃.ResultsThe calibration curves were linear in the ranges of 0.25－2.01 μg·mL-1 for quercetin and 2.54－20.32 μg·mL-1 for rutin. The average rates of recovery of quercetin and rutin were 98.7%(RSD＝1.26%) and 99.2%(RSD＝1.07%),respectively.ConclusionThe method was shown to be rapid, accurate and well reproducible.
    • 用药指南
  • 用药指南
    In Vitro Bacteriostatic Effects of Piperacillin/tazobactam on Pathogenic Bacteria Commonly Encountered in the Clinic
    SHI Dongyan;YANG Jingfang;WANG Xin;LI Zhongxing
    2006, 25(2): 0-0.
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    ObjectiveTo survey and compare the in vitro bacteriostatic effects of domestic and imported piperacillin/tazobactam on Pathogenic bacteria commonly encountered in the clinic.MethodsBacterial suspensions were separately prepared for each of the 336 strains of bacteria to be tested. Escherichia coli 25922 and Pseudomonas aeruginosa 27853 surved as the quality control bacteria strains. The in vitro bacteriostatic effects of various drugs were assayed with the doubled agar dilution method. Sensitivity of bacteria to drugs was calculated according to the marginal antibiotics＇ concentration to which the bacteria were sensitive. ResultsDomestic piperacillin/tazobactam was shown to have excellent bacteriostatic effects on Klebsiella pneumoniae I super broad spectrum β-lactamase positive (ESBLs＋), K.pneumoniae(ESBLs), E.coli(ESBLs＋), E.coli(ESBLs) and a fairly good inhibitory effect on P. aeruginosa. Piperacillin/tazobactam was also shown to have the best in vitro bacteriostatic effects as compared with those of cefoperazone/sulbactam(CFP/SUB), cefotaxime/sulbactam (CTX/SUB), amoxicillin/clavulaniate potassium(AMO/CLK), and ampicillin/sulbactam(AMP/SUB). Besides, the enterobacteriaceae manifested almost the same sensitivity to domestic and imported piperacillin/tazobactam and the 2 kinds of the drug showed equivalent bacteriostatic effects on P. aerllginosa.ConclusionPiperacillin/tazobactam was shown to have excellent in vitro bacteriostatic effects and domestic and imported products of the drug were comparable in this respect.
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