Design of a new line in treatment of experimental rheumatoid arthritis by artesunate

This study was aimed to evaluate the therapeutic potency of a new antimalarial drug, artesunate, in an experimental model of rheumatoid arthritis. Collagen-induced arthritis (CIA) was induced in Lewis rats.The intraperitoneally administration of artesunate (ARS) and methotrexate (MTX) were started on day 25 postimmunization and continued until final assessment on day 35. During this period, clinical examination was intermittent. The anticollagen type II antibody (CII Ab) and nitric oxide synthesis were measured. The paws and kness were then removed for histopathology and radiography assay. The biocompatibility of ARS and MTX were assessed using fibrosarcoma cell line. Our results showed that i.p. injection of artesunate to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed reduced inflammatory cells infiltrate in joints of treated rats, and tissue edema and bone erosion in the paws were markedly reduced following ARS therapy. Moreover, our radiographic results paralleled histological findings. Cytotoxicity analysis of ARS showed greater tolerability compared with MTX. Treatment with ARS significantly diminished nitric oxide formation in treated rats compared with untreated controls. Our findings revealed the therapeutic efficacy of artesunate in experimental rheumatoid arthritis compared with a choice drug (methotrexate). This result may recommend it as a second-line drug in the treatment of rheumatoid arthritis.     

血吸虫病治疗药物研究进展

本文主要综述了国内外血吸虫病治疗药物的发展史,以及吡喹酮、青蒿琥酯、蒿甲醚和一些中草药在治疗和控制血吸虫病中的作用。     

伯氏疟原虫对青蒿素抗药性的研究

仿Peters剂量递增法用伯氏疟原虫ANKA株及N株对QHS进行了抗药性的研究。经14个月的培育至第58代,QHS im注射“4日抑制性实验”的ED_(50)在RQ/ANKA系及RQ/N系分别为其亲代系的53.4及54.6倍,但经蚊传未获成功。在第40代(I_(50)=25)时,其50%的治愈剂量为其亲代系的5.4倍。停药传代其抗性会逐渐消失。该虫系对青蒿酯钠及蒿甲醚有明显的交叉抗性,其ED_(50)分别为其亲代系的13.1及11.7倍,对伯喹的抗性为2.9倍,对氯喹未见明显交叉抗性。     

青蒿琥酯对乙酰氨基酚诱导的小鼠急性肝损伤的保护作用研究

目的探讨青蒿琥酯在对乙酰氨基酚诱导的小鼠急性肝损伤中的保护作用及其机制。方法建立对乙酰氨基酚诱导的急性肝损伤模型,将小鼠随机分为对照组、模型组、联苯双酯组和青蒿琥酯低、中、高剂量组。通过检测肝脏血清中的谷丙转氨酶(ALT)、谷草转氨酶(GOT)、肝组织匀浆中的丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)水平及肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平,检测肝细胞的凋亡率、观察肝脏病理学改变,评价青蒿琥酯在对乙酰氨基酚诱导的小鼠急性肝损伤中的保护作用。结果与对照组比较,模型组ALT、GOT、MDA水平显著升高,GSH和SOD水平显著下降(P <0.05),炎症因子TNF-α、IL-6水平和肝细胞凋亡率显著升高(P <0.05),说明造模成功。与模型组比较,青蒿琥酯组ALT、GOT及MDA水平显著下降,GSH和SOD水平显著上升(P <0.05);炎症因子TNF-α、IL-6水平和肝细胞凋亡率显著下降(P <0.05),并有效减轻肝细胞的坏死程度。结论青蒿琥酯在对乙酰氨基酚诱导的小鼠急性肝损伤中具有明显的保护作用,其机制可能与其抗氧化作用、减少炎症反应及抑制细胞凋亡有关。     

Inhibition of angiogenesis in vivo and growth of Kaposi's sarcoma xenograft tumors by the anti-malarial artesunate

Artesunate (ART) is a semi-synthetic derivative of the sesquiterpene artemisinin used for the second line therapy of malaria infections with Plasmodium falciparum. ART also inhibits growth of many transformed cell lines. In the present investigation, we show that ART inhibited the growth of normal human umbilical endothelial cells and of KS-IMM cells that we have established from a Kaposi's sarcoma lesion obtained from a renal transplant patient. The growth inhibitory activity correlated with the induction of apoptosis in KS-IMM cells. Apoptosis was not observed in normal endothelial cells, which, however, showed drastically increased cell doubling times upon ART treatment. ART strongly reduced angiogenesis in vivo in terms of vascularization of Matrigel plugs injected subcutaneously into syngenic mice. We conclude that ART represents a promising candidate drug for the treatment of the highly angiogenic Kaposi's sarcoma. As a low-cost drug, it might be of particular interest for areas of Kaposi's sarcoma endemics. ART could be useful for the prevention of tumor angiogenesis.     

中药加小剂量干扰素治疗急性输血后丙型肝炎21例

中药加小剂量干扰素治疗急性输血后丙型肝炎２１例巩合义，郭秀兰１９９０年１月～１９９６年１月，我们应用４种方法比较治疗急性输血后丙型肝炎共８１例，现报告如下。临床资料８１例均符合同型肝炎诊断标准［中华传染病杂志１９９１；９（１）：５２］随机分为４组。Ⅰ...     

现场应用青蒿琥酯预防日本血吸虫感染的效果

目的： 观察现场应用青蒿琥酯预防日本血吸虫感染的效果。方法： １９９７ 年７ ～９ 月, 分别在望江县杨河试区及贵池市沙山试区选择易感人群５６２ 例与２１８ 例, 将受试者随机分为两组, 按双盲法分服青蒿琥酯和安慰剂, 剂量均为６ ｍｇ／ｋｇ 顿服, 受试者在接触疫水后２ ｗｋ 开始服药, 每２ ｗｋ １ 次, 连服４ 次, 接受全程试验者末次服药后４ ｗｋ , 用尼龙绢集卵法加改良加藤法进行效果评价。结果： 杨河试区服药组２７３ 例中２ 例孵化阳性,阳性率为０７ ％ ; 对照组２８９ 例粪检阳性１１ 例, 阳性率为３８ ％ , Ｅ Ｐ Ｇ 为２６４０ ±１４９ 个。沙山试区服药组１０７例粪检均为阴性, 对照组１１１ 例粪检阳性７ 例, 感染率为６３ ％ , Ｅ Ｐ Ｇ 为１４２３ ±２１４ 个。两试区青蒿琥酯预防血吸虫感染的保护率分别为８０９ ％ 与１００ ％ 。结论： 口服青蒿琥酯能有效地预防日本血吸虫感染。     

青蒿琥酯对小鼠玫瑰痤疮样炎症的作用观察

目的 观察青蒿琥酯对小鼠玫瑰痤疮样炎症的影响.方法 在25只7周龄BALB/c雄鼠背部皮下注射40μl抗菌肽LL-37,每12小时1次,共4次,制备玫瑰痤疮样小鼠模型,并将其随机等分为5组,每次注射LL-37后模型组给予生理氯化钠溶液灌胃,治疗组分别给予25、50、100 mg/kg青蒿琥酯溶液灌胃,阳性对照组给予30 mg/kg盐酸多西环素溶液灌胃;另取5只小鼠作为空白对照组,仅背部皮下注射4次纯水.首次注射LL-37后48 h观察各组皮损和红斑评分,取背部注射部位皮肤行HE染色,观察组织结构并计数炎症细胞数量,ELISA法检测皮损髓过氧化物酶(MPO)活性.结果 模型组皮损炎症反应明显,红斑评分(3.20±0.84)、炎症细胞计数(517.27±99.43)和MPO活性(0.57±0.08)均显著高于空白对照组(均P＜0.01),阳性对照组红斑评分(1.60±0.89)、炎症细胞计数(270.93±124.63)和MPO活性(0.40±0.05)均显著低于模型组,差异有统计学意义(P＜0.05、0.01、0.01).50和100 mg/kg青蒿琥酯组红斑评分分别是1.80±0.84和1.40±0.55,显著低于模型组(P＜0.05、0.01),炎症细胞计数分别为286.00±33.72和258.00±36.44,显著低于模型组(均P＜0.01),MPO活性分别是0.43±0.05和0.40±0.06,亦明显低于模型组(P＜ 0.05、0.01).50 mg/kg和100 mg/kg青蒿琥酯组红斑评分、炎症细胞计数和MPO活性与阳性对照组差异均无统计学意义.结论 青蒿琥酯能抑制小鼠玫瑰痤疮样炎症反应,以中、高剂量最为明显.     

Effects of artesunate-cotrimoxazole and amodiaquine-artesunate against asexual and sexual stages of <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> malaria in Nigerian children

The activities of artesunate-cotrimoxazole and artesunate-amodiaquine combinations against asexual-and sexual-stage parasites were evaluated in 182 Nigerian children with uncomplicated Plasmodium falciparum malaria. One hundred and twenty-one children received artesunate-cotrimoxazole and 61 received artesunate-amodiaquine and all were followed up for 28 days. Clinical recovery from illness occurred in all children. There was no significant difference in fever clearance time (P = 0.35). Both treatment groups achieved a parasite clearance time of less than 2 days (1.84 +/- 0.66 days and 1.31 +/- 0.48 days); gametocyte carriage rates were comparable in the two treatment groups prior to and following treatment; both treatments appeared to reduce gametocyte carriage. The pretreatment gametocyte sex ratio, which was female-biased, was maintained throughout the period of follow up in both treatment groups. Reduction of gametocyte carriage by these two treatment regimens may reduce transmissibility in P. falciparum malaria, and this reduction is presumed to be related to the accelerated clearance of the asexual forms of the parasite.