OBJECTIVE:To establish an HPLC method for determination of ganciclovir in serum of dogs and to study pharmacokinetics and relative bioavailability of Ganciclovir dispersible tablets.METHODS:The determination was performed on Dikma DiamonsilTM C18 column.The mobile phase consisted of 0.015 mol?mL-1 monobasic potassium phosphate buffer solution (pH 2.50,containing 0.25% acetonitrile) with flow rate of 1.75 mL?min-1 at detection wavelength of 254 nm.The column temperature was set at 40 ℃.In a randomized cross-over study,a single dose of dispersible tablets and the capsule were given to 6 dogs.An HPLC method was used to determine plasma concentration of ganciclovir in dogs and the pharmacokinetic data were treated by DASver1.0 software.RESULTS:The linear range of ganciclovir were 0.050 25～100.5 ?g?mL-1;the methodological recovery was larger than 90% (RSD

Objective To explore the developmental toxicity of aluminum sulfate and its mechanism. Methods 8.5-day-old embryos of Kunming mice were explanted and cultured in a whole embryo culture system with Al 3+ concentrations of 0.6, 0.9, 1.2, 3.0, 6.0, 9.0 ?g/ml for 48 h. Each viable embryo was evaluated using Maele-Fabry scoring system, and visceral yolk sac diameter, crown-rump and head length, and embryo dry weight were measured, as well as GSH activity in embryonic tissue by using 5,5-dithion-bis-2-nitrobenzoic acid (DTNB), and membrane lipid fluidity of visceral yolk sac cell by DPH fluorescence polarization technique. Results Al 2(SO 4)3 at Al 3+ concentration of 3 ?g/ml resulted in significant inhibition of development of embryos and differentiation of organs, and increasing prevalance rate of abnormal embryos including open neural tube, small head abnormality and deficit in flexion. At Al 3+ concentration of 6.0 ?g/ml, the activity of GSH and the membrane lipid fluidity of visceral yolk sac decreased significantly. In a certain degree, the dose-effect(response) relationship were observed in the above hazardous effects induced by Al 2(SO 4)3. Conclusion Al 2(SO 4)3 presented potential teratagenicity and embryotoxicity, which might be associated with the decreases of the membrane lipid fluidity of visceral yolk sac and the activity of GSH both induced by Al 2(SO 4)3.

Objective To explore the effects of chemical reaction of aluminum salt in water solution on developmental toxicity Methods Inhibiting actions on embryo growth and development,and organ morphogenetic differentiation in rats induced by newly prepared and 11 5 month stored aluminum sulfate solution were observed and compared using whole embryo culture method in rats Results Both of the two observed solutions showed a certain embryo toxicity and teratogenicity The toxicity of stored solution decreased significantly compared with that of newly prepared solution At the same concentration of aluminum,the total Brown's morphogenetic score reflecting the every index of embryo growth and development and organ morphogenetic differentiation,the incidence rates of terata and the number of dead embryos were significant lower in rats exposed to stored solution compared with those exposed to newly prepared solution,especially the morbidity of embryos Conclusion The complexation reaction between aluminum ions (Al 3+ ) and water molecules in stored aluminum sulfate solution resulted in the changes of existing state of Al 3+ and its decreasing developmental toxicity to rats

OBJECTIVE:To introduce the operation instructions and routine maintenance method of horizontal laminar flow cabinet(HLFC) in PIVAS to provide reference for standardized operation of HLFC.METHODS:The standardized utilization and maintenance of HLFC in respects of compositions,operation principle,operation instructions,etc.RESULTS & CONCLUSIONS:The standardized operation and correct maintenance can ensure the dispensation quality of intravenous drugs and extend service life of HLFC.

0.05). Conclusion The assumable reasons for the dominance of heterozygous ADH2 genotype were a relatively small size of samples or gene mutation etc,which needed further researches to be confirmed.The proportion of individuals carrying about "susceptible genotypes of alcohol_related diseases"in female child_bearing ages was more than one half (0.617),which called on the reinforce of the surveillance on and prevention of alcohol_related birth (ARBD).

re To understand the developmental toxicity of aluminum and its mechanism. Methods The embryos of SD rats at the 9. 5th day after gestation were explanted and cultured in a whole-embryo culture system with exposure to AlCl3 at Al3+ concentrations of 0.6, 0.9, 1.2, 3.0, 6.0 and 9.0 ?g/ml for 48 hours. Using Brown's mor-phological scoring system, yolk sac diameter, crown-rump length, head length and embryonic dry weight were mea-sured. Results A certain dose-effect relationship (r= - 0.890? 0.973, P

8 ?mol/L)was markedly restrained. Zearalenone, like estradiol, could markedly increase the proliferation of MCF-7 cells. The effects were time-dependent and dose-dependent. Conclusion: The tested phytoestrogens are biologically active, and they can differently affect the proliferation of human breast cancer cells in vitro. These data suggest that genistein may have preventive and therapeutic applications against breast tumors.

Objective To determine the effects of organic extracts of drinking water on female mice reproductive system.Methods The Kunming female mice were randomly divided into4groups,one as reagent control group,the other three as treated groups,15female mice per group.The treated groups were treated with the organics extracted from the chlorinated drinking water by the solid phase extraction at the doses of12.5,25and50L/kg respectively,once a day,continuously for5d.The pathological changes of ovary were observed by optical microscopy.Results At the10th day after treatment,the number of intermediate follicles andⅡatretic follicles in ovary in the treated group significantly increased,especially the number ofⅡa-tretic follicles in25L/kg group,which was10times as high as that in the control group.At the30th day after treatment,the number of normal follicles revealed no significant changes,the number ofⅡatretic follicles in the25and50L/kg group was still significantly higher than that in the control group,the number of corpora lutea in ovary significantly decreased with the in-creases of doses.The estrous cycle delayed at the level of50L/kg.Conclusion The organic extracts from drinking water had adverse effects on the female reproductive system by affecting the development and maturity of the follicles.

Objective To establish a method to investigate micronuclei (MN) and gene mutation at the heterozygous thymidine kinase (tk) locus induced by environmental mutagens in TK6 human lymphoblastiod cells. Methods TK6 cells were used to detect cytotoxic response, MN and mutation frequency at tk locus induced by cyclophosphomide (CP) after treatment with S9 mixture for 4 h. Results Exposure to CP for 4 h decreased relative survival (RS), induced both MN and TK mutation in a concetration-dependent manner. The maximum induction of MN and TK mutations were 8.8 and 15.7 times compared with those of control. Two distinct phenotypic colonies of TK mutants were generated, namely tk-NG and tk-SG mutant colonies but mainly the latter. Conclusion CP induced both MN and TK mutation in TK6 cells. TK6 cells can be used as an in vitro assay system to assess cytogenetic damage and gene mutation at tk locus of environmental chemicals.

Objective To investigate the effects of p53 protein and mRNA expression in rat liver tumor promotion by phenobarbital(PB). Methods Male Wistar rats were randomly divided into 6 groups,i. e. higher dose group,middle dose group,lower dose group,tumor-initiating control group,tumor-promoting group and normal control group. The rat liver tumor DEN-initiating-PB-promoting model was established among higher dose group,middle dose group,lower dose group and tumor-initiating control group. The rats in higher dose group,middle dose group and lower dose group were fed with feed containing 500,100,50 mg/kg PB respectively. The rats in liver-tumor promoting control group were only fed with normal feed. The rats in tumor-promoting group weren't initiated by DEN,were only fed with feed containing 500 mg/kg PB. The rats in normal control groups weren't treated by any factors. At the 1st,5th,10th,15th,20th,30th week of the exposure to PB,the expression of p53 protein and p53 mRNA of the rats in every group were determined by immunohistochemistry and in situ hybridization respectively. Results The expression of the mutant type p53(mtp53) protein was found in liver tumor-initiated rats which revealed precancerous lesion. The expression of p53 protein of rats increased in higher and middle dose groups,and showed higher levels in lower dose group and liver tumor-initiating control group compared with those of normal control group which didn't variate significantly with the prolongation of period of exposure to PB. The expression of wild type p53 (wtp53) mRNA showed lower levels in rats of normal control group and liver tumor-promoting group,showed higher levels in higher dose group,middle dose group,lower dose group and liver tumor-initiating control group compared with those in normal control group. The expression of wtp53 mRNA decreased in higher dose group and middle dose group,increased a little in lower dose group and liver-tumor-initiating with the prolongation of period of exposure to PB. Conclusion During the promoting stage of rat liver tumorigenesis tumor promotor PB might reduce the expression of wtp53 and induce mtp53 expression,which affected the cell cycle arrest and apoptosis,and might favor clonal expansion of preneoplastic hepatocytes,which promoted the formation of liver tumor.