Combination therapy using drugs with different mechanisms of action is the current state of the art in antimalarial treatment. However, except for artemisinin-based combination therapies, only a few other combinations are now available. Increasing concern regarding the emergence and spread of artemisinin resistance in Plasmodium falciparum has led to a need for the development of new antimalarials. Moreover, the efficacy of current available chemoprophylaxis is compromised by drug resistance and noncompliance due to intolerable adverse effects or complicated dosing regimens.

Objective To observe the antitumor effect of artemisinin and its derivatives in vitro.Methods Microculture tetrazolium assay was applied to test the cytotoxicity of artemisinin,dihydroartemisinine,artemether and artesunate to human lung cancer A549 cell line,human gastric cancer BGC823 cell line,human colon carcinoma HCT116 cell line,human erythroleukemia K562 cell line and human hepatocarcinoma SMMC7721 cell line in vitro.Results Artemisinin,dihydroartemisinine,artemether and artesunate showed selective cytotoxicity to these five tumor cell lines.Conclusion Artemisinin,dihydroartemisinine,artemether and artesunate have different antitumor activities in vitro.

Objective To establish a rapid and sensitive LC-MS-MS method for the analysis of artemisinin in the plasma and study the pharmacokinetics of artemisinin tablets in healthy volunteers.Methods Ten healthy male volunteers were received oral single dose artemisinin tablets(1 000 mg).The plasma samples were determined by L-MS-MS method.Results The limits of quantitation of method for artemisinin was 4 μg·L-1,the calibration curves in plasma was linear in the range of 4 to 1 000 μg·L-1.The pharmacokinetic parameters were as follows : Cmax was(466.50±120.15) μg·L-1;AUC0-24h was(2.78±0.85) mg·h·L-1;AUC0–∞ was(2.82±0.87) mg·h·L-1;t1/2 was(3.58±0.86) h;tmax was(2.15±0.91) h.Conclusion The method is shown to be accurate and convenient,and suitable for pharmacokinetic study of artemisinin.

Objective:To determine the inhibitory effect of compounds L20051117 and AMMS607 on influenza virus neuraminidase at molecular level.Methods:The anti-influenza virus neuraminidase activity of L20051117 and AMMS607 was examined by the fluorimetric assay.Results:The inhibitory effect of L20051117 on influenza virus neuraminidase was higher than that of AMMS607,the inhibition of influenza A virus neuraminidase by L20051117 and AMMS607 was higher than that of influenza B virus neuraminidase.Conclusion:L20051117 is a potent inhibitor of the neuraminidase activity of both influenza A and B virus.Its in vitro activity is higher than AMMS607.

Resistance has become a big obstacle to the cure of malaria. As the leading medicament, quinolines used to be widely used but now the invalidation is deteriorating. In this article, the research progress in the relationship of resistance-related genes pfcrt, pfmdr1 and cg2 to the resistant mechanism of quinolines is reviewed.

Radix Isatidis (Banlangen in Chinese) is a traditional Chinese medicinal (TCM) herb, and is frequently used for treating influenza. However, the current quality control method for Radix Isatidis should be developed since it has little correlation to the pharmacodynamic action. In this paper, the in vitro inhibitory action of Radix Isatidis on neuraminidase (NA) was investigated by fluorometric assay with 4-methylumbelliferyl-D-N-acetylneuraminate (FL-MU-NANA) method. Based on the method, the experimental condition was optimized and a bioassay statistic method was established according to the reaction type and the regularity of "parallel lines of qualitative effect". Then the bioassay method of Radix Isatidis was established. This study indicated that Radix Isatidis had obvious in vitro inhibitory activity on NA with IC50 = (0.90 +/- 0.20) mg x mL(-1) (herb). The correlation between logarithmic dose and reaction rate showed an "S" shape--is quite similar to Tamiflu's reaction curve, which hinted that Radix Isatidis had the same inhibitory function on NA as Tamiflu. The established bioassay method of "parallel lines of qualitative effect" had a good reproducibility (RSD = 5.78%). The results of potency determination of Radix Isatidis were reliable (reliability test: deviation from straight line P > 0.05, deviation from parallel line P > 0.05) and well regular. As a conclusion, this bioassay method is suitable to control and evaluate the quality of Radix Isatidis.

目的 观察金振口服液对Vero E6细胞内SARS相关冠状病毒的抑制作用.方法 取一定量的SARS相关冠状病毒BJ-01株加入培养好的Vero E6细胞中,置37℃、5%CO2培养箱吸附2 h,吸出病毒液,再分别加入不同浓度的药物稀释液,在同样条件下培养4～5 d,观察细胞病变情况.结果 金振口服液抑制冠状病毒半数有效浓度(IC50)为2.0μg/mL,治疗指数(TI)为35,,结论金振口服液对SARS病毒有较好的抑制作用.

Peters 4d inhibition test were used to determine the antimalarial activity of different ingredients of Artemisia annua L.and their combinations with Qinghaosu(QHS)on P.berghei.The ED_50 and ED_90 of QHS are(10.2±1.3)and(29.0±2.7)mg/kg/d respectively;and those of QHH(Qinghaosu:Qinghao acid:Qinghao B:Scopoletin=1:1:1:1)are(12.6±1.1)and(47.0±5.7)mg/kg/d respectively.Qinghao acid(QHA),Qinghao B(QHB),Scopoletin(QHC),Casticin(QHD)and Chrysosplenol D(QHE)had some antimalarial activities on P.berghei.Even when the dosage was up to 500 mg/kg/d,the maximal inhibition rate was only 59%,which is less active than QHS.Therapeutic effect of different ingredients of A.auuna and QHS combinations on P.berghei appeared synergistic effects only with high dosage of QHC.Although QHS only accounts for 1/4 in QHH,QHH and QHS have similar antimalarial activity.The results revealed that the mixture of QHA,QHB and QHC enhanced the antimalarial activity of QHS on P.berghei.It was proved that the antimalarial activity of QHS primarily together with other ingredients of A.annua is the result of the antimalarial activity on P.berghei of A.annua in the study.

To observe the effect of Qinghao extract and artemisinine on the ultrastructure of Plasmodium berghei by Peters four-day oral treatment.The result showed membrane structure of the protozoon trophozoit was damaged by Qinghao extract and artemisinine.The polypide surface membrane,food vacuole membrane,restriction membrane,mitochondrial membrane,endoplasmic reticulum and nuclear membrane swelled.The intermembrane space widened.Some polypide surface membrane and food vacuole membrane showed multilayer thread-like change.Serve pathological changed protozoon trophozoit were cataplasis and their structure disappeared.The red blood cell contained the residual food vacuole and phagocytotic vesicle.The Qinghao extract and artemisinine had the inhibitory action on the development of merozoite in the plasmodium.Qinghao extract had the same effect on the damaged location of ultrastructure and character of pathological changes as the artemisinine.Meanwhile Qinghao extract and artemisinine had some effect on the development of the merozoite in the parasitophorous vacuole of plasmodium.

OBJECTIVE To study the antimalarial activity of naphthoquine phosphate combined with artemisinine against Plasmodium knowlesi in rhesus monkey. METHODS Monkeys were randomly divided into 9 groups (3/group). The monkeys in groups A and B were treated i.g. once daily for 3 days with 6 or 10 mg/kg of naphthoquine phosphate respectively. Those in groups C and D were treated i.g. twice for the 1st day and once for the 2nd and 3rd day with 31.6 or 100 mg/kg of artemisinine respectively. In groups E, F and G, they were treated i.g. only once with the combination of naphthoquine phosphate 10 mg/kg and artemisinine 10, 20 or 25 mg/kg respectively. Groups H and I served as controls which were treated i.g. only once with 10 mg/kg of naphthoquine phosphate and 30 mg/kg of artemisinine respectively. Parasitemia was examined beginning 24 h after drug administration. The observation lasted 105 days when no more parasite was found. RESULTS At 24 h after drug administration, the parasite reduction rate in all groups was higher than 90%. The parasite clearance time for groups E, F and G was (56.0 +/- 16.0), (53.3 +/- 4.6), and (56.0 +/- 8.0) h respectively, more rapid than that of Group H [(69.3 +/- 4.6) h]. There were 1, 3, 3, 2, 2, and 3 monkeys in groups A, B, D, E, F, and G respectively which were cured. No monkeys were cured in groups C, H and I. CONCLUSION The combination of naphthoquine phosphate and artemisinine is superior to the single component and the optimum proportion in the combination is 1 : 2.5 in treating P. knowlesi infection in monkeys.

Aim To evaluate the anti-SARS-CoV effect of interferon-α,interferon-γ and the combination of interferon-α and interferon-γ at 5 different ratios in vitro.Methods The antiviral activity of interferon-αand interferon-γ was determined by MTT colorimetry.Results The TCID50 of SARS-CoV was 10-7.Interferon-α and interferon-γ had anti-SARS-CoV activity in vitro.The anti-SARS-CoV effect of Interferon-α was better than that of interferon-γ.And the anti-SARS-CoV effect of the combination of Interferon-α and interferon-γ was better than that of any single drug.Conclusion Interferon-α,interferon-γ and the combination of interferon-α and interferon-γ all have anti-SARS-CoV activity in vitro.This study has provided experimental evidence for the clinical use of antiviral treatment of the SARS-CoV infection.

To study the pharmacodynamic effect of naphthoquine phosphate and its combination with artemisinin in mice infected with Plasmodium berghei. Applying orthogonal design and "4 d suppressive test" to study the optimum proportion of synergetic effect. By gradually increasing drug pressure during successive weekly passages of P. berghei infection in mice, cultivate drug-resistance of P. berghei to naphthoquine phosphate, artemisinin and its combination respectively,up to 100 passages. The optimum proportion of naphthoquine phosphate and artemisinin was 1∶50. The pharmacodynamic tests revealed that the combination of these two drugs was synergetic, the synergetic indices were 4.2 and 8.2 that calculated from chloroquine-sensitive strain of P.bergher or chloroquine-resistent strain of P.bergher, respectively. The curative effects of the combination against P.bergher in mice were superior to the drug used in single. After 100 passages, the resistant indices of naphthoquine phosphate, artemisinin and the combination were 200.3, 5.6 and 4.4 respectively. The tests confirmed that the naphthoquine phosphate and its combination with artemisinin exhibited a synergetic activity against P.bergher in mice. It was also revealed that the combination could delay the emergence of drug resistance and reduce its resistance level.

真菌多糖被称为生物反应调节剂,多糖及其复合物的研究已成为今年生物学、医学等领域的研究热点之一.本文在广泛收集目前国内外文献资料的基础上,针对桑黄多糖的免疫功能研究现状就其多方面的免疫调节作用做一综述.

Artemisinin and its derivatives with endoperoxide function are new and important antimalarial drugs,and their antimalarial action is quick,efficient and without cross resistance.It is generally agreed that artemisinins' action mechanism is associated with the endoperoxide function,but some researchers have some other ideas.Up to the present,drugs like chloroquine,mefloquine and pyrimethamine have brought clearly drug resistance,and owing to the unique chemical constitution,artemisinins are the only drugs without drug resistance.So,finding their action mechanism is far important to avoid bringing the resistance and prolong their service life.

痘病毒是所有病毒中最大、最复杂的病毒。致死性的正痘病毒仍然威胁着人类的健康。虽然在20世纪70年代末,世界卫生组织宣布天花病毒已经在全球范围内被消灭,但是,还是存在天花出现的可能性。因此,各国科学家仍在积极寻找能够有效对抗天花病毒及其他能够导致疾病和死亡的痘病毒的药物。西多福韦是全球研究最多、最深入的一个药物,其余处于研究阶段的药物还包括常用的抗病毒药、酶抑制剂及其他核苷类药物等。

Objective:To establish the normal hematological indexes and biochemical indexes of clean Wistar rat.Methods: 110 male and 110 female clean Wistar rats of 10～12 weeks old were selected.The indexes of hematology and biochemistry were measures.Results: WBC and ALT were much higher in males than in females(P0.01),while the creatinine and TP in males were lower in males than in females(P0.01).Conclusions: The normal value ranges of these indexes are coincident with those reported in relevant literature.

In order to know the safety of compound sodium dichloroisocyanurate disinfection powder,toxicological evaluation was carried out in laboratory.Results: In mouse acute oral toxicity test,the LD_(50) of the compound sodium dichloroisocyanurate disinfection powder was 5000 mg/kg·bw(95% confidence limits were 4811～7328),indicating that it is practically non-toxic.Subacute toxicity test found no abnormalities in animal blood routine,blood biochemical indexes and various organs.The skin irritation index was 0.5,indicating that the irritation intensity belongs to no irritability.It did not cause micronucleus formation in mouse bone marrow polychromatic erythrocytes and has no teratogenic effect on mouse sperms.Conclusions: Under the conditions of present experiment,the compound sodium dichloroisocyanurate disinfection powder is practically non-toxic and not irritating to rabbit skin,does not cause micronucleus formation and has no teratogenic effect.

Aim: To investigate the anti-tumor activities of crude polysaccharides(PL) from the mushroom Phellinus linteus on transplanted tumor in mice and observe the effects on the functions of peritoneal macrophages(PM) in vitro.Method: Anti-tumor activities were assayed by weighing tumor weight.LDH release assay was utilized for measuring PM-mediated lysis of tumor cell.The TNF-α secretion of PM was measured by Elisa assay.Result: PL at regimen 250,500 and 1000mg/kg.day ×10 day inhibited evidently the development of transplanted tumor in mice,in vitro PL a dose 100μg/ml up-regulated PM-mediated cytotoxicity and enhances TNFα secretion of PM in dose-dependent manner.Conclusion: PL inhibited evidently the development of transplanted tumor in mice,enhancing PM function and up-regulation of TNF-αtumor activity.

In order to study the toxicity of compound chlorhexidine acetate disinfectant for skin and mucosa,animal test method was used for toxicological evaluation.Results: Using chlorhexidine acetate as the evaluating dosage,the mouse acute oral LD_(50) of the disinfectant was 20 g/kg body weight,which practically belongs to nontoxic category.The stock solution of the disinfectant was non-irritating to rabbit skin and eye mucous membrane.In vaginal mucosa irritation test,histopathological examination of vaginal mucosa of 3 rabbits found various degrees of congestion,edema,leukocyte infiltration and distortion of tissue.The average irritation score was 1.9 which meant mild irritation.In subacute toxicity test,28 days after the rats of 3 dosage groups received the drug,the results of measurement of 10 blood biochemical indices and 6 hematological indices did not show significant change as compared with those of the normal control group.Histopathological examination of 10 organs did not find significant abnormality.The percentrges of PCE with micronucleus induced by 3 dosages showed no significant difference as compared with that of the negative control group(P0.05),indicating no mutagenic effect on mouse bone marrow PCE.Conclusion: The disinfectant belongs to practically nontoxic category and did not show abnormal change in subacute toxicity evaluation.It was slightly irritating to rabbit vaginal mucous membrane.

目的 BC是以醋酸氯已定为主要成分的一种用于皮肤粘膜的杀菌液.本试验依据卫生部颁布的<消毒技术规范>对该产品进行安全性评价.