To characterize the preclinical pharmacokinetics, tissue distribution and excretion profiles of exendin-4 in healthy Wistar rats were studied. Exendin-4 was radioiodinated by the IODOGEN （1,3,4,6-tetrachloro-3 alpha,...To characterize the preclinical pharmacokinetics, tissue distribution and excretion profiles of exendin-4 in healthy Wistar rats were studied. Exendin-4 was radioiodinated by the IODOGEN （1,3,4,6-tetrachloro-3 alpha, 6 alphadiphenylglucoluril） method. Pharrnacokinetic properties of ^125I-exendin-4 were examined after a single s.c. and i.v. injection, respectively. Tissue distri- bution and urinary, fecal, and biliary excretion patterns of ^125I-exendin-4 were also investigated following a single s.c. injection. Exendin-4 was rapidly distributed and cleared with t1/2 of （0.48 ± 0.03） h after a single i.v. injection. Following a single s.c. administration, exendin-4 exhibited rapid and considerable absorption with Tmax of （0.25± 0.02） h and declined with the elimination t1/2 of（1.28± 0.14） h. The absolute bioavailability was （65.5 ± 10.2） %. The radioactivity was widely distributed and rapidly diminished in most tissues. The kidney contained the highest radioactivity and the distribution of ^125I-exendin-4 to the brain was minimal. The major elimination route was urinary excretion. The pharmacokinetic properties of exendin-4 obtained from the present study closely matched those reported in previous studies in rats. Pharmacokinetics profiles of exendin-4 in rats are warranted for the design of future clinical trials.展开更多
Twenty-two nitrate nonutilizing （nit） mutants were recovered from five wild-type isolates of Fusarium graminearum and fifty nit mutants were recovered from three JS399-19-resistant mutants of F. graminearum cultured...Twenty-two nitrate nonutilizing （nit） mutants were recovered from five wild-type isolates of Fusarium graminearum and fifty nit mutants were recovered from three JS399-19-resistant mutants of F. graminearum cultured on MMC medium. Some biological properties were compared between nit mutants and their parental isolates. The results showed that there were no significant differences in growth rate, cultural characters or pathogenicity between JS399-19-resistant nit mutants and their parental isolates. But the conidial production and the sexual reproduction ability changed to some extent. There was no cross resistance toward chlorate and JS399-19 in F. graminearum and the resistance could be stable through 20-time subcultures. Therefore, the nit could be used as a genetic marker for studying the genetics of JS399-19 resistance in E graminearum, which was used to study JS399-19 resistance transferability in hyphal fusion. Resistance in JS399-19 could not be transferred by hyphal fusion or could be transferred with low chance between two compatible isolates, which would delay the development of JS399-19 resistance in the field.展开更多
48 patients with liver fibrosis due to hepatitis B were treated for 2 years with the drugs for tonifying the kidney, supplementing qi, cooling and invigorating the blood and detoxification. The symptoms were markedly ...48 patients with liver fibrosis due to hepatitis B were treated for 2 years with the drugs for tonifying the kidney, supplementing qi, cooling and invigorating the blood and detoxification. The symptoms were markedly improved, and serum ALT and bilirubin were recovered and kept normal in most of the cases. The mean levels of serum hyaluronic acid, procollagen peptide III and circulating immune complex were decreased and returned to normal after the treatment. B-ultrasonography showed that the portal vein kept in normal size in 82% of the patients, the enlarged portal vein diminished in diameter, and the enlarged spleen reduced.展开更多
AIM:To find a rapid and efficient analysis method of gastrointestinal microflora in Pi-deficient(spleen-deficient) rats and to evaluate traditional Chinese drugs.METHODS:Enterobacterial repetitive intergenic consensus...AIM:To find a rapid and efficient analysis method of gastrointestinal microflora in Pi-deficient(spleen-deficient) rats and to evaluate traditional Chinese drugs.METHODS:Enterobacterial repetitive intergenic consensus-PCR(ERIC-PCR) based assay was performed to examine changes of intestinal microflora in two Pi-deficienct animal models and to evaluate the efficacy of four traditional Chinese drugs as well as a probiotic recipe and another therapy in Pi-deficient rats.RESULTS:A molecular marker was identified for Pi-deficiency in rats.The pharmacodynamic evaluation system,including identified molecular markers(net integral area and abundance of DNA bands),Shannon's index for diversity of intestinal microflora,and Sorenson's pairwise similarity coefficient,was established.The four major clinical recipes of traditional Chinese drugs for Pi-deficiency in rats,especially at their medium dose(equivalence to the clinical dose),produced more pronounced recovery activities in Pi-deficient rats,while higher doses of these recipes did not show a better therapeutic effect but some toxic effects such as perturbation deterioration of intestinal microflora.CONCLUSION:Both fingerprint analysis and identified marker can show Pi-deficiency in rats and its difference after treatment.The identified molecular marker may be applied in screening for the active compounds both in relative traditional Chinese drugs and in pharmacodynamic study of Pi-deficiency in rats.展开更多
Solid phase exchange radioiodination method was used to label the compound.Pharmacokinetics was studied in rats and the data were dealt with by computer. The results indicate that the compound would be a potential myo...Solid phase exchange radioiodination method was used to label the compound.Pharmacokinetics was studied in rats and the data were dealt with by computer. The results indicate that the compound would be a potential myocardial imaging agent.展开更多
Hydroxypropyl chitosan(HP-chitosan) has been shown to have promising applications in a wide range of areas due to its biocompatibility, biodegradability and various biological activities, especially in the biomedical ...Hydroxypropyl chitosan(HP-chitosan) has been shown to have promising applications in a wide range of areas due to its biocompatibility, biodegradability and various biological activities, especially in the biomedical and pharmaceutical fields. However, it is not yet known about its pharmacokinetics and biodegradation performance, which are crucial for its clinical applications. In order to lay a foundation for its further applications and exploitations, here we carried out fluorescence intensity and GPC analyses to determine the pharmacokinetics mode of fluorescein isothiocyanate-labeled HP-chitosan(FITC-HP-chitosan) and its biodegradability. The results showed that after intraperitoneal administration at a dose of 10 mg per rat, FITC-HP-chitosan could be absorbed rapidly and distributed to liver, kidney and spleen through blood. It was indicated that FITC-HP-chitosan could be utilized effectively, and 88.47% of the FITC-HP-chitosan could be excreted by urine within 11 days with a molecular weight less than 10 k Da. Moreover, our data indicated that there was an obvious degradation process occurred in liver(< 10 k Da at 24 h). In summary, HP-chitosan has excellent bioavailability and biodegradability, suggesting the potential applications of hydroxypropyl-modified chitosan as materials in drug delivery, tissue engineering and biomedical area.展开更多
基金National High Technology 863 Project (Grant No. 2003AA2Z347B)
文摘To characterize the preclinical pharmacokinetics, tissue distribution and excretion profiles of exendin-4 in healthy Wistar rats were studied. Exendin-4 was radioiodinated by the IODOGEN （1,3,4,6-tetrachloro-3 alpha, 6 alphadiphenylglucoluril） method. Pharrnacokinetic properties of ^125I-exendin-4 were examined after a single s.c. and i.v. injection, respectively. Tissue distri- bution and urinary, fecal, and biliary excretion patterns of ^125I-exendin-4 were also investigated following a single s.c. injection. Exendin-4 was rapidly distributed and cleared with t1/2 of （0.48 ± 0.03） h after a single i.v. injection. Following a single s.c. administration, exendin-4 exhibited rapid and considerable absorption with Tmax of （0.25± 0.02） h and declined with the elimination t1/2 of（1.28± 0.14） h. The absolute bioavailability was （65.5 ± 10.2） %. The radioactivity was widely distributed and rapidly diminished in most tissues. The kidney contained the highest radioactivity and the distribution of ^125I-exendin-4 to the brain was minimal. The major elimination route was urinary excretion. The pharmacokinetic properties of exendin-4 obtained from the present study closely matched those reported in previous studies in rats. Pharmacokinetics profiles of exendin-4 in rats are warranted for the design of future clinical trials.
基金This work was supported by the State "973" Programs from the Ministry of Science and Technology of China (No. 2006CB101900)Technology and the Project (No. 20050307028)+3 种基金from the Ministry of Education of China, the National Natural Science Foundation of China (No. 30671048 & No. 30671384)Jiangsu Provincial Program for Tackling Key Problems of Science and Technology (No. BG2006328)the Key Technology R & D program from the Ministry of Science and Technology of China (No. 2006BAE01A04-08)the state "863" programs from the Ministry of Science and Technology of China (No. 2006AA10A211).
文摘Twenty-two nitrate nonutilizing （nit） mutants were recovered from five wild-type isolates of Fusarium graminearum and fifty nit mutants were recovered from three JS399-19-resistant mutants of F. graminearum cultured on MMC medium. Some biological properties were compared between nit mutants and their parental isolates. The results showed that there were no significant differences in growth rate, cultural characters or pathogenicity between JS399-19-resistant nit mutants and their parental isolates. But the conidial production and the sexual reproduction ability changed to some extent. There was no cross resistance toward chlorate and JS399-19 in F. graminearum and the resistance could be stable through 20-time subcultures. Therefore, the nit could be used as a genetic marker for studying the genetics of JS399-19 resistance in E graminearum, which was used to study JS399-19 resistance transferability in hyphal fusion. Resistance in JS399-19 could not be transferred by hyphal fusion or could be transferred with low chance between two compatible isolates, which would delay the development of JS399-19 resistance in the field.
文摘48 patients with liver fibrosis due to hepatitis B were treated for 2 years with the drugs for tonifying the kidney, supplementing qi, cooling and invigorating the blood and detoxification. The symptoms were markedly improved, and serum ALT and bilirubin were recovered and kept normal in most of the cases. The mean levels of serum hyaluronic acid, procollagen peptide III and circulating immune complex were decreased and returned to normal after the treatment. B-ultrasonography showed that the portal vein kept in normal size in 82% of the patients, the enlarged portal vein diminished in diameter, and the enlarged spleen reduced.
基金Supported by The National Natural Science Foundation of China,No.90209059Supported by The National Natural Science Foundation of China,No.90409018
文摘AIM:To find a rapid and efficient analysis method of gastrointestinal microflora in Pi-deficient(spleen-deficient) rats and to evaluate traditional Chinese drugs.METHODS:Enterobacterial repetitive intergenic consensus-PCR(ERIC-PCR) based assay was performed to examine changes of intestinal microflora in two Pi-deficienct animal models and to evaluate the efficacy of four traditional Chinese drugs as well as a probiotic recipe and another therapy in Pi-deficient rats.RESULTS:A molecular marker was identified for Pi-deficiency in rats.The pharmacodynamic evaluation system,including identified molecular markers(net integral area and abundance of DNA bands),Shannon's index for diversity of intestinal microflora,and Sorenson's pairwise similarity coefficient,was established.The four major clinical recipes of traditional Chinese drugs for Pi-deficiency in rats,especially at their medium dose(equivalence to the clinical dose),produced more pronounced recovery activities in Pi-deficient rats,while higher doses of these recipes did not show a better therapeutic effect but some toxic effects such as perturbation deterioration of intestinal microflora.CONCLUSION:Both fingerprint analysis and identified marker can show Pi-deficiency in rats and its difference after treatment.The identified molecular marker may be applied in screening for the active compounds both in relative traditional Chinese drugs and in pharmacodynamic study of Pi-deficiency in rats.
文摘Solid phase exchange radioiodination method was used to label the compound.Pharmacokinetics was studied in rats and the data were dealt with by computer. The results indicate that the compound would be a potential myocardial imaging agent.
基金financially supported by National High Technology Research and Development Program of China(863 Program,Grant No.2007AA091603)
文摘Hydroxypropyl chitosan(HP-chitosan) has been shown to have promising applications in a wide range of areas due to its biocompatibility, biodegradability and various biological activities, especially in the biomedical and pharmaceutical fields. However, it is not yet known about its pharmacokinetics and biodegradation performance, which are crucial for its clinical applications. In order to lay a foundation for its further applications and exploitations, here we carried out fluorescence intensity and GPC analyses to determine the pharmacokinetics mode of fluorescein isothiocyanate-labeled HP-chitosan(FITC-HP-chitosan) and its biodegradability. The results showed that after intraperitoneal administration at a dose of 10 mg per rat, FITC-HP-chitosan could be absorbed rapidly and distributed to liver, kidney and spleen through blood. It was indicated that FITC-HP-chitosan could be utilized effectively, and 88.47% of the FITC-HP-chitosan could be excreted by urine within 11 days with a molecular weight less than 10 k Da. Moreover, our data indicated that there was an obvious degradation process occurred in liver(< 10 k Da at 24 h). In summary, HP-chitosan has excellent bioavailability and biodegradability, suggesting the potential applications of hydroxypropyl-modified chitosan as materials in drug delivery, tissue engineering and biomedical area.
