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 (Al3+) and water molecules in stored aluminum sulfate solution resulted in the changes of existing state of Al3+ and its decreasing developmental toxicity to rats.

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 explore the potential hazards of organic pollutants in chlorinated drinking water on human reproduction.Methods　The reproductive toxicity of the organic pollutants extracted by solid phase extraction technique from chlorinated drinking water in a city,was determined by the co-culture of sertoli cells and spermatogenic cells.Results　No significant variation of the rate of detached spermatogenic cells was noticed compared with the control rats.The organic extracts stimulated the secretion of lactate from sertoli cells of testis in rats.Conclusion　The organic extracts of chlorinated drinking water revealed potential reproductive toxicity.

Objective　To explore the mechanism of male reproductive toxicity of bisphenol-A.Methods　The morphological characteristics of seminiferous tubule,vimentin filaments and p53 gene expression in sertoli's cells of adult SD rats orally exposed to 0.5% bisphenol-A were observed and analyzed by histo-chemical and immuno-histochemical methods.Results　After 2-week-exposure to 0.50% bisphenol-A,the disattachment between sertoli's cell and spermatogonia,spermatogonia arranged in disorder and displacement of spermatogonia away from the basement membrance of seminiferous tubules as well as the flocculated chromatins of nuclei in sertoli's cells and spermatogonia were observed.Fourfold increase of p53 expression in nuclei of spermatogonia and leydig's cells and the collaps of vimentin filaments in sertoli's cells were also found.Conclusion　The results suggested that the disattachment between sertoli's cells and spermatogonia,might be associated with the collaps of vimentin filaments in nuclei of sertoli's cells and the increase of p53 expres sion in nuclei of sertoli's cells and spermatogonia,which might be one of the important mechanisms of reproductive toxicity of bisphenol-A.The increase of p53 expression in nuclei of leydig's cells might predict the potential anti-androgenicity of bisphenol-A

Objective To study the toxicokinetics of phthalates in male rabbits. Methods Concentrations of DEHP or DBP in plasma of 6 healthy male rabbits were determined by RP-HPLC after constant rate infusion of 0.5 g/kg DEHP or DBP(IV). The toxicokinetic parameters were computed by 3P87 program. Results The toxicokinetic model of DEHP and DBP were both first-order elimination and two-compartment model with constant rate infusion. The main toxicokinetic parameters of DEHP were as follows: distribution phose t1/2(?)=0.101 h; elimination phase t1/2(?)=12.701 h; CLs=0.013 g?kg-1?h-1. The main toxicokinetic parameters of DBP were as follows: t1/2(?)=0.441 h; t1/2(?)=31.311 h; CLs=0.021 g?kg-1?h-1. Conclusion DEHP and DBP were both first order elmination and two-compartment medol with constand rate intusion(IV). DEHP and DBP could be rapidly eliminated in male rabbits.

4.67, P

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