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The fluorescence spectroscopy and UV spectroscopy have been used to monitor the inclusion phenomena of VP-16 with beta-cyclodextrin (beta-CD), together with studies concerning the effects of reaction time, temperature and concentration on this behavior. The results show that the fluorescence intensity increased when VP-16 and beta-CD forming a 1 : 1 inclusion complex, which indicate that beta-CD has fluorescence sensitizing effect on the VP-16. At 22 degrees C, the inclusion constant was 2.63 x 10(5) L x mol(-1) at pH 7.0. VP-16 has maximum emission wavelength at 316 nm under the optimum conditions. According to this, the quantitative micro-detection method of VP-16 by fluorescence spectrometry was established. The linear regression equation was y = 1.107 89 x 10(70 x + 95.898 1, with a correlation coefficient of 0.999 9. The detection limit was 2.094 x 10(-7) mol x L(-1).

This study is to explore the possible mechanisms of the antidepressant-like effect of agmatine. By using two traditional "behavior despair" model, tail suspension test and forced swimming test, we examined the effects of some monoamine receptor antagonists (including beta-adrenergic receptor antagonist propranolol, beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol, alpha2-adrenergic receptor antagonists yohimbine and idazoxan and 5-HT3 receptor antagonist tropisetron) on the antidepressant-like action of agmatine in mice. Activity of adenylate cyclase (AC) in the synapse membrane from rat frontal cortex was determined by radioimmunoassay. Single dose of agmatine (5-40 mg x kg(-1), ig) dose-dependently decrease the immobility time in tail suspension test in mice, indicating an antidepressant-like effect. The effect of agmatine (40 mg x kg(-1), ig) was antagonized by co-administration of beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol (20 mg x kg(-1), ip), alpha2-adrenergic receptor antagonists yohimbine (5-10 mg x kg(-1), ip) or idazoxan (4 mg x kg(-1), ip), but not beta-adrenergic receptor antagonist propranolol (5-20 mg x kg(-1), ip) and 5-HT3 receptor antagonist tropisetron (5-40 mg x kg(-1), ip). Agmatine (5-40 mg x kg(-1), ig) also dose-dependently decrease the immobility time in forced swimming test in mice. The effect of agmatine (40 mg x kg(-1), ig) was also antagonized by pindolol (20 mg x kg(-1), ip), yohimbine (5-10 mg x kg(-1), ip), or idazoxan (4 mg x kg(-1), ip). Incubation of agmatine (0.1-6.4 micromol x L(-1)) with the synaptic membrane extracted from rat frontal cortex activated the AC in a dose-dependent manner in vitro. While the effect of agmatine (6.4 micromol x L(-1)) was dose-dependently antagonized by pindolol (1 micromol x L(-1)) or yohimbine (0.25-1 micromol x L(-1)). Chronic treatment with agmatine (10 mg x kg(-1), ig, bid, 2 w) or fluoxetine (10 mg x kg(-1), ig, bid, 2 w) increased the basic activity, as well as the Gpp (NH)p (1-100 micromol x L(-1)) stimulated AC activity in rat prefrontal cortex. These results indicate that regulation on 5-HT1A/1B and alpha2 receptors, and activation AC in the frontal cortex is one of the important mechanisms involving in agmatine's antidepressant-like action.

Aim: To study the anticancer effect of artesunate and its mechanism., Methods: To observe the effect of artesunate on the growth of solid tumor and the expression of PCNA, Bcl-2 and Bax genes in mice bearing H22 solid hepatic carcinoma., Results: After administration of artesunate (ig, 300 mg.kg-1.d-1 x 7 d), growth of solid tumor was obviously inhibited, the tumor inhibitory rates were 49.1%, 48.7% and 46.6% and 46.6% in 3 experiments. The apoptosis of liver cancer cells were increased. Immunohistochemical staining showed that the number of Bcl-2 protein positive cells were decreased, but the number of Bax protein positive cells were increased. The PCNA positive cells were significantly lower than those in the control group., Conclusion: Artesunate showed obvious anticancer activity on H22 hepatic carcinoma bearing mice and undergo apoptosis of liver cancer cells. The mechanism of anticancer effect of artesunate may be related to down-regulation of the expression of PCNA and Bcl-2 genes and up-regulation of the expression of Bax gene.

The cytochrome P-450 (Cyt P-450) sensitive to mepyramine (HP-450) in liver microsome is a protein that possesses properties of both H1 receptor and cytochrome P-450. We used [3H]mepyramine radioligand binding assay and enzymological technique to study the kinetic properties of HP-450 and Cyt P-450. Age-related changes in the Bmax, Kd of HP-450 and Cyt P-450 in rat hepatic microsome were demonstrated. The levels of Bmax for both HP-450 and the Cyt P-450 dramatically increased in the postnatal period from the second to the eighth week, and reached maximum steady status during the eighth to tenth week. The values of Bmax of HP-450 correlated well with the content of Cyt P-450 in rat liver microsome (r = 0.625). The affinity of HP-450 (Kd) decreased with the growth of rats during postnatal. No sexual-related difference was observed in this experiment.