青蒿酯钠的抗疟机理

青蒿酯钠(sodium artesunate,SA)在碱性条件下可产生超氧阳离子(O_2~-)和过氧化氢(H_2O_2)等活性氧;在pH 7.4条件下虽不能产生活性氧,但可使红细胞中O_2~-和H_2O_2等活性氧的浓度升高,并能增加红细胞膜的脂质过氧化.SA使疟原虫感染红细胞的活性氧增加和膜脂质过氧化程度均比未感染红细胞显著.     

青蒿琥酯抗肿瘤作用的机制研究

青蒿琥酯 (ａｒｔｅｓｕｎａｔｅ ,ＡＳＴ)是我国研制的抗疟药。文献[1,2 ] 报道青蒿琥酯有抗肿瘤作用 ,体外试验还能诱导人肝癌细胞凋亡 ,对Ｐ5 3表达无明显影响。尚未见有青蒿琥酯对在体肿瘤细胞中增殖细胞核抗原 (ＰＣＮＡ) ,Ｂｃｌ 2和Ｂａｘ基因的影响的报道。本实验进一步探讨青蒿琥酯抗肿瘤作用及其作用机制。材料与方法　　药物与试剂　注射用青蒿琥酯 ,桂林第二制药厂产品 ,批号 0 0 0 10 1,先用 5 %ＮａＨＣＯ3溶解后用生理盐水配制成所需浓度 ;5 氟尿嘧啶针剂 (5 ＦＵ) ,上海旭东海普药业有限公司产品 ,批号 9912 0 5 ;抗ＰＣ…     

恶性疟原虫对青蒿酯钠抗性的体外培育

恶性疟原虫FCR_3在体外采用剂量递增间隔接触方法在青篙酯钠的作用下产生了对该药的抗药性。在接触药物前,青蒿酯钠对该虫株裂殖体成熟抑制的半数抑制浓度(IC_(50))为1.6ng/ml(4.1nmol/L),经过130d间隔接触药物后,虫株对青蒿酯钠的敏感性下降,其IC_(50)值增高至约为亲代系的3倍,即4.7ng/ml(12.2nmol/L)。抗性系在去除药物作用后,其抗性水平很快下降。     

Efficacy and tolerability of artesunate‐amodiaquine (Camoquin plus®) versus artemether‐lumefantrine (Coartem®) against uncomplicated Plasmodium falciparum malaria: multisite trial in Senegal and Ivory Coast

Objective To compare, in a phase IV trial, the efficacy and tolerability of artesunate‐amodiaquine (Camoquin plus®) dosed at 300 and 600 mg of amodiaquine per tablet to artemether‐lumefantrine (Coartem®) for the treatment of Plasmodium falciparum uncomplicated malaria in Ivory Cost and Senegal. Method Multisite, randomised, open‐labelled study in patients over the age of 7 years. The primary endpoint for efficacy was adequate clinical and parasitological response (ACPR) at day 28. The secondary endpoints were fever and parasite clearance and gametocyte carriage in each treatment group. Drug tolerability was assessed comparing adverse events and modification of biological parameters between D0 and D7. Data were analysed on an intention‐to‐treat and per protocol basis. Results We included 322 patients; 316 patients completed the monitoring to D28 (155 in AS + AQ group and 161 in AL group). In ITT analysis, an ACPR corrected rate of 97.4% was observed in AS + AQ group versus 97% in AL group (P = 0.99). No parasite recrudescence was observed in AS + AQ arm. All patients in both groups had a fever and parasite clearance at D2. Gametocytes had disappeared by D14 in the AL group and by D21 in the AS + AQ group. No serious adverse events were observed. Minor adverse events were significantly more frequent in the AS + AQ arm. Biological parameters between D0 and D7 did not show any significant statistical variations except for anaemia. Conclusion This study demonstrates the efficacy and tolerability of AS + AQ for uncomplicated Plasmodium falciparum malaria treatment in African patients over the age of 7 years.     

青蒿琥酯对人胚肺成纤维细胞系HFL—I细胞增殖、凋亡的影响及机制

目的进一步探讨青蒿琥酯的抗纤维化作用及机制。方法取对数生长期人胚肺成纤维细胞（HELF）系HFL-I细胞株,随机分为观察1—4组及对照组,观察1-4组分别加入质量浓度为4、8、16、32mg／L的青蒿琥酯,对照组加入等体积培养液后继续培养。用CCK-8法检测细胞增殖情况（A值）,流式细胞仪检测细胞周期及凋亡率,RT-PCR法测定Survivin mRNA表达。结果观察1-4组G0＋G1期细胞所占比例及细胞凋亡率均显著高于对照组,细胞A值及Survivin mRNA表达均显著低于对照组,且各观察组间亦有显著差异（P〈0．05）。结论青蒿琥酯具有抗肺纤维化作用,可能机制为通过下调Survivin mRNA表达抑制HFL-I细胞增殖、促进HFL-I细胞凋亡。     

转铁蛋白增强青蒿琥酯对A549细胞增殖抑制活性

目的研究转铁蛋白增强青蒿琥酯对A549细胞的增殖抑制活性。方法采用MTr法检测青蒿琥酯单用或合用转铁蛋白对肺癌A549细胞的增殖抑制作用。结果青蒿琥酯对A549细胞的IC50值为144．76mg·L^-1,青蒿琥酯合用转铁蛋白后IC50值降为45．89mg·L^-1。结论转铁蛋白增强了青蒿琥酯对A549细胞的增殖抑制活性。     

青蒿琥酯对人胃腺癌MKN45细胞株增殖抑制和诱导凋亡作用

目的研究青蒿琥酯(ART)对人胃腺癌MKN45细胞株的体外增殖抑制和诱导凋亡作用,并探讨其作用机制。方法以不同浓度的ART作用于体外培养的人胃腺癌MKN45细胞株,采用四甲基偶氮唑盐比色法(MTT)检测细胞生长抑制率;应用流式细胞仪检测细胞凋亡情况;用Western Blotting法检测不同浓度的ART作用于MKN45细胞株时凋亡相关蛋白B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、半胱天冬蛋白酶9(caspase-9)和半胱天冬蛋白酶3(caspase-3)等表达情况。结果 MTT实验显示,ART作用48 h后对MKN45细胞增殖有显著抑制作用,抑制作用随着药物浓度的增加而递增(P<0.05),IC50值为13.41μmol.L-1。13.41μmol.L-1ART对MKN45细胞增殖存活有明显的抑制作用,且对细胞抑制作用与药物作用时间和浓度呈正相关(P<0.05)。随着ART浓度的增加,ART对MKN45细胞凋亡率逐渐升高(P<0.05)。ART使MKN45细胞Bcl-2蛋白表达明显降低,Bax、caspase-9及caspase-3蛋白表达明显增高,并随药物浓度的增加,其对凋亡相关蛋白表达的调控作用也明显增强。结论 ART能体外抑制人胃腺癌MKN45细胞株的生长并诱导细胞发生凋亡。     

健康人对青蒿琥酯片的耐受性和不良反应

以双盲法对22名健康男性志愿者进行青蒿琥酯片口服的耐受性和不良反应研究。结果:最大耐受量,单次给药为12mg/kg,5d连续给药为4mg/(kg·d);不良反应,最敏感的指标是网织红细胞下降,其次是转氨酶升高.建议青蒿琥酯片口服治疗量暂定为2mg/(kg·d),首剂加倍,5d疗程总量12mg/kg。     

我国近几年抗疟药研究新进展

综述了我国抗疟药研究的新进展。自1985年以来有三种新药和一种制剂在国内注册,它们是:蒿甲醚、青蒿琥酯、本芴醇和青蒿素栓剂;新药萘酚喹和蒿甲醚-本芴醇复方正进行第Ⅱ期临床试验。此外,咯萘啶与其他药物伍用亦取得进展。     

What is the effect of combining artesunate and praziquantel in the treatment of Schistosoma mansoni infections?

A group of 110 individuals with Schistosoma mansoni infection was investigated. Patients were allocated to one of three treatment groups and given artesunate or praziquantel alone or both in combination. Combined artesunate-praziquantel significantly increased the number of individuals cured at 5 weeks post-treatment, but at 12 weeks was only better than artesunate alone and at 24 weeks there was no statistically significant difference between the three groups. Egg count reduction rate was similar to the rate obtained with praziquantel used alone.