Objective To study the effect and mechanism of the apoptosis of hypertrophic scar fibroblasts (HSF) induced by artesunate(Art). Methods HSFs were isolated and cultured from human earlobe scars by the tissue adherence method. The 3th to 5th generation cells were harvested and divided into two groups. HSF was cultured with normal medium in control group and with medium containing60, 120 and 240 mg/L (5 ml)Art in experimental group. Apoptosis and cell cycle were identified by light microscopy, electronmicroscopy and flow cytometry. Then, HSF was cultured with normal medium in control group and with medium containing 30, 60 and 120 mg/L Art in experimental group. The changes of intracellular calcium concentration were observed. Results The primary HSF was fusiform in shape and adherent. The vimentin positive expression was analyzed by immunocytochemistry. Art could induce apoptosis of HSF in the range of 60-240 mg/L under inverted microscope. The effect was dose and timedependent. Clumping of nuclear chromatin showed margination in the experimentalgroup. And the disaggregation of the nucleolus were observed under electronmicroscopy. There were significant differences in the proportion of HSF apoptosis and HSF at G0-G1,S, G2-M stages between the two groups(P＜0.05). Apoptotic peak was shown in experimental group by flow cytometry. The peak became more evident asArt concentration increased. The intracellular calcium concentration elevated markedly in HSF with 30-120 mg/L Art treatment for 24 hours, showing significant differences between the two groups (P＜0.05). Conclusion The Art facilitates HSF cells apoptosis in vitro by the change of cell cycle. It is suggested that intracellular calcium variation may be one of the mechanisms of HSF apoptosis induced by Art.
Objective To investigate the effects of two formulations of artesunate, and to provide evidence for the WHO Model List of Essential Medicines. Methods We searched The Cochrane Library (2006, Issue 4), MEDLINE ( 1966 to 2007), EMbase (1988 to 2007), CBM (1978 to 2007), VIP (1989 to 2007) and CNKI (1994 to 2007). Randomised trials comparing the two formulations of artesunate with other drugs were eligible for inclusion. We applied the methods of The Cochrane Collaboration to assess the effects of artesunate, compared to placebo and active controls. Results Eleven trials were included, of which 6 compared intravenous artesunate with intravenous quinine. The quality of each study was high, 6 out of the 11 studies were graded A according to the criteria of The Cochrane Collaboration. The other 5 were graded B. The meta-analysis suggested that the mortality rate was lower in the intravenous artesunate group than in the intravenous quinine group [RR 0.65, 95%CI (0.52, 0.80), Plt;0.0001]. Three trials compared intravenous artesunate with artemisinin suppositories. These trials generated similar estimates and confidence intervals for mortality rates, showing no significant difference between the two treatments [0.94 (0.35 to 2.56), 0.58 (0.19 to 1.74) and 2.00 (0.39 to 10.26)]. Two trials compared intravenous artesunate and intramuscular artesunate, and no significant difference in mortality rate was identified between the two treatment groups [RR 1.50, 95%CI 0.52 to 4.31]. Mortality rates were not statistically significantly different for intravenous artesunate compared to alternative drugs. No significant adverse drug reactions were observed. Conclusions Artesunate is effective and safe in the treatment of severe malaria.