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71.
72.
青蒿琥酯下调人喉癌细胞所致 T 细胞免疫抑制的体外实验研究 总被引:1,自引:0,他引:1
目的:体外实验研究青蒿琥酯( ART)对人喉癌细胞所致T细胞免疫抑制的影响。方法制备经ART预处理的人喉癌Hep-2细胞培养上清(ART-S),收集连续2次再培养的上清(分别称为ART-S1、ART-S2),以不经ART作用的Hep-2及其上清作对照;分析对人外周血单个核细胞经光镜观察、噻唑蓝( MTT)法测定的植物血凝素( PHA)诱导淋巴细胞转化增殖反应,以及流式细胞计数(FCM)法检测的T淋巴细胞表面CD3ε+、CD3ε+ζ+、IL-2Rα+表达的影响。结果 Hep-2对5项免疫指标的抑制率分别为(52?.58±6.13)%、(50.34±7.26)%、(45.28±5.38)%、(39.74±5.27)%、(64.25±9.37)%。 ART作用后,可显著下调Hep-2所致T细胞免疫抑制( P <0.01);第1次再培养后,对淋巴细胞转化、诱导增殖、IL-2Rα表达抑制的逆转均明显降低,与ART-S比较差异有统计学意义( P <0.01),对CD3ε+及CD3ε+ζ+表达抑制的逆转持续增强,与ART-S比较差异有统计学意义( P <0.05);第2次再培养后,对淋巴细胞转化、诱导增殖、IL-2Rα表达抑制的逆转继续保持,与ART-S1比较差异无统计学意义( P>0.05),对CD3ε+、CD3ε+ζ+表达抑制的逆转明显下降回复至 ART-S水平,差异无统计学意义( P >0.05)。结论人喉癌Hep-2细胞可产生T细胞免疫抑制作用,ART可对其产生稳定的逆转作用。下调肿瘤免疫抑制是ART的重要抗瘤机制之一。 相似文献
73.
The combination of artesunate and mefloquine is one of the most effective treatments against multidrug-resistant falciparum malaria. Experience in children is however limited. The objective of this study was to compare the efficacy and safety of two artesunate/mefloquine combinations with artesunate monotherapy in Ecuadorian children. A total of 150 children with an age between 2 and 12 years, confirmed to have uncomplicated falciparum malaria, were randomly selected and divided in three treatment groups of 50 patients each. Group 1 received 50 mg rectal capsules alone (40 mg/kg total dose) administered over 6 days. Group 2 received 50 mg rectal capsules (30 mg/kg total dose) for 3 days combined with mefloquine (20 mg/kg total dose) on day 1. Group 3 was treated with 50 mg rectal capsules (30 mg/kg total dose) for 3 days, combined with mefloquine on days 1 and 3 (15-17 mg/kg total dose). Patients were continuously followed up and controlled by clinical and laboratory examinations for 7 days as well as on days 14, 21 and 28. An additional parasite examination was performed at 2 months following therapy. Clearance of parasitaemia was comparable between treatment groups. These were 9.2, 9.2 and 8.3 h for Groups 1, 2 and 3, respectively. Cure rates at day 28 were 76, 96 and 94% and after 2 months 60, 88 and 80%, respectively. There were no adverse events (AEs) reported during the study. Vital signs and laboratory examinations revealed no changes of clinical relevance. It can be concluded that the combination of artesunate rectal capsules with mefloquine is effective and safe. Starting concomitant administration already on day 1 is well tolerated. This combination significantly reduces the incidence of recrudescence compared to artesunate monotherapy. Comparing the two tested artesunate/mefloquine regimens, a total mefloquine dose of 20 mg/kg seems to be more effective compared to a total dose of 15-17 mg/kg. Further studies seem to be warranted. 相似文献
74.
75.
Gaudin K Langlois MH Barbaud A Boyer C Millet P Fawaz F Dubost JP 《Journal of pharmaceutical and biomedical analysis》2007,43(3):1019-1024
Stability of artesunate (ART) was established in three pharmaceutical solvents. The chromatographic conditions developed for this study were acetonitrile:potassium phosphate buffer 10 mM (40:60, v:v; pH 2.9) at 0.7 mL min(-1) with UV detection at 220 nm using a short X-Terra RP C18 column (50 mm x 3 mm, 3.5 microm). This isocratic condition led to the separation between ART and its main degradation products (i.e. alpha-DHA and beta-DHA) with analysis time of less than 4 min. The retention factors are 1.49, 2.26 and 2.79 min for alpha-DHA, beta-DHA and ART, respectively. This method was proved linear (r(2)=0.9995), accurate (R.S.D.=0.20), precise (R.S.D.=0.74) and robust. The system performance remained unaffected by pH variation from 2.6 to 3.2 and variation of acetonitrile percentage from 38 to 42. Stability of ART was assessed in ethanol, propylene glycol (PG) and polyethylene glycol 400 (PEG 400). Unfortunately none of these solvents prevented ART from degradation longer than 3 months. In ethanol, significant degradation of ART occurred after 3 months at room temperature and this degradation was characterised by numerous degradation products. In PEG 400, significant degradation was observed after only 1 month, however DHA was the unique degradation product, which is also an efficient anti-malarial drug. 相似文献
76.
Lack of impact of artesunate on the disposition kinetics of sulfadoxine/pyrimethamine when the two drugs are concomitantly administered 总被引:1,自引:1,他引:0
Minzi OM Gupta A Haule AF Kagashe GA Massele AY Gustafsson LL 《European journal of clinical pharmacology》2007,63(5):457-462
Objective
To determine the effect of artesunate (AT) on the disposition kinetics of sulfadoxine/pyrimethamine (SP) in humans.Methods
In a randomized cross-over study, 16 healthy volunteers were given a dose of three SP tablets containing 500 mg of sulfadoxine (SDX) and 25 mg of pyrimethamine (PYR) (=SP group), while the second arm received three SP tablets + two AT tablets of 200 mg in total followed by 100 mg AT for the next 4 days (SP+AT group). Blood samples (100 μl) were collected by means of a finger prick and dried on filter paper. The blood spots were wrapped in polythene folders and stored at room temperature until analysis. The samples were assayed using high-performance liquid chromatographic methods.Results
The peak concentration Cmax), time required to attain peak concentration (Tmax), half-life (t ½) and area under the plasma concentration-time curve (AUC) were determined. The Cmax of SDX were 92.9 and 98.9 μg/ml for the SP and SP+AT arms, respectively; for PYR, these were 0.86 and 0.79 μg/ml, respectively. The Tmax of SDX were 10 and 8 h for the SP and SP+AT arms, respectively; for PYR, these were 4.0 and 3.0 h, respectively. The AUC0–288 of SDX were 15,840 and 18,876 μg/ml h for the SP and SP+AT arms, respectively; for PYR, they were 124 and 112 μg/ml h, respectively. The t ½ of values for SDX were 165 and 180 h for the SP and SP+AT arms, respectively; for PYR, these were 158 and 177 h, respectively. There was no statistically significant difference between the Cmax, Tmax, AUC0–288 and t ½ between the two arms (p?>?0.05).Conclusion
Taking AT concomitantly with SP does not have any impact in the disposition of SP.77.
Design of a new line in treatment of experimental rheumatoid arthritis by artesunate 总被引:2,自引:0,他引:2
Mirshafiey A Saadat F Attar M Di Paola R Sedaghat R Cuzzocrea S 《Immunopharmacology and immunotoxicology》2006,28(3):397-410
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. 相似文献
78.
目的验证青蒿琥酯对佐剂性关节炎大鼠血清及滑膜细胞原代培养上清液中单核细胞趋化因子(MCP)-1、调节正常T细胞表达和分泌因子(RANTES)和肿瘤坏死因子(TNF)-α的影响。方法取雄性Wistar大鼠80只建立佐剂性关节炎大鼠模型,第6天选出右后足和两前足关节炎指数之和≥6分的60只大鼠,随机数字表法分为空白对照组、模型对照组、甲氨蝶呤阳性药物对照组(简称甲氨蝶呤组)和青蒿琥酯大剂量[20mg/(kg.d)]、中剂量[10mg/(kg.d)]、小剂量组[2.5mg/(kg.d)]并灌胃给药。给药免疫后第8天处死大鼠,抽取静脉血,取血清。同时无菌操作取各组大鼠膝关节滑膜组织行原代培养后培养48h,离心收集上清液。采用酶联免疫吸附试验(ELISA)观察各组治疗前后血清及滑膜细胞原代培养上清液MCP-1、RANTES及TNF-α浓度变化。结果青蒿琥酯大、中、小剂量组能显著降低血清及上清液中细胞因子TNF-α,与模型对照组比较,差异有统计学意义(P<0.05),青蒿琥酯大、中剂量组与甲氨蝶呤组比较,差异无统计学意义(P>0.05),而青蒿琥酯小剂量组与青蒿琥酯大、中剂量组及甲氨蝶呤组比较,差异均有统计学意义(P<0.05);青蒿琥酯各剂量组能显著降低血清及上清液中炎性趋化因子MCP-l和RANTES的表达,与模型组比较,差异有统计学意义(P<0.05),而与甲氨蝶呤组比较,差异无统计学意义(P>0.05)。结论青蒿琥酯抗炎和免疫调节作用可能与抑制炎症因子TNF-α及趋化因子MCP-1、RANTES相关。 相似文献
79.
血吸虫病治疗药物研究进展 总被引:2,自引:2,他引:0
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。 相似文献
80.
Campbell P Baruah S Narain K Rogers CC 《Transactions of the Royal Society of Tropical Medicine and Hygiene》2006,100(2):108-118
A four-arm drug sensitivity study compared chloroquine, sulfadoxine-pyrimethamine (SP), mefloquine and mefloquine-artesunate in Sonitpur and Karbi Anglong districts in Assam state, India. Two criteria were used to ascertain outcome: success of clinical treatment and parasitologic cure. In Sonitpur, at 14 days, there were 36/56 early and late treatment failures plus late parasitologic failures to chloroquine and 16/56 for SP. In Karbi Anglong, combined treatment failure at 14 days was 16/56 to chloroquine and 8/60 to SP. Mefloquine and mefloquine-artesunate demonstrated 93.9% and 93.6% sustained responses respectively at 42 days. High failure rates to both chloroquine and SP preclude the use of these drugs as first-line treatment for uncomplicated falciparum malaria in this region. A mefloquine-artesunate combination presents an effective alternative utilizing the currently recommended higher dose of mefloquine. 相似文献