抗咯萘啶的伯氏疟原虫感染红细胞多胺量的测定

目的：了解疟原虫的多胺代谢与咯萘啶（ＰＮＤ）抗药性的关系。方法：感染伯氏疟原虫ＡＮＫＡ株（ＰＳ）和由该株培育的中抗ＰＮＤ品系（ＰＲＡ）及高抗ＰＮＤ品系（ＰＲＢ）的昆明株小鼠于腹腔接种（ｉｐ）后ｄ７取血，经薄层层析后用荧光分光光度法测定正常ＲＢＣ、ＰＳ、ＰＲＡ和ＰＲＢ感染ＲＢＣ的丁二胺（ＰＴＣ）、精脒（ＳＰＤ）和精胺（ＳＰＭ）量。另有感染ＰＳ和ＰＲＢ的小鼠于ｉｐ后ｄ６分别１次灌胃（ｉｇ）ＰＮＤ５ｍｇ／ｋｇ和１０ｍｇ／ｋｇ，ｄ７取血，按上述方法测定给药后感染ＲＢＣ的多胺量，并与不给药组比较。结果：ＰＳ感染ＲＢＣ的多胺量均明显高于未感染疟原虫的正常ＲＢＣ，而感染ＰＲＡ和ＰＲＢ的ＲＢＣ多胺量又显著高于ＰＳ感染ＲＢＣ，且多胺量的增高与抗性程度有关。经ＰＮＤ治疗后ＰＳ感染ＲＢＣ的ＳＰＤ和ＳＰＭ较未治疗组显著下降，而ＰＲＢ感染ＲＢＣ则未见明显变化。结论：伯氏疟原虫对ＰＮＤ的抗药性与其多胺代谢有关。     

云南省恶性疟流行概况及其对氯喹的抗性

云南省是我国恶性疟主要流行区。历史上分布于北纬２５°以南的高、中疟区６５个县（市），海拔１２００ｍ以下的地区。１９８０年全省恶性疟发病数已控制至１０１９例，仅占当年疟疾疫情报告数的３．１６％。由于流动人口的剧增，国外传染源的输入，抗氯喹株恶性疟的扩散，１９９２年恶性疟病例上升至５３７９例，比１９８０年增加４．２８倍，已占全省疟疾疫情报告数的３０．５６％，报告恶性疟的县（市）数已达７４个。几年来通过恶性疟原虫对抗疟药敏感性监测，结果表明氯喹及哌喹抗性程度仍然严重。本文概述了云南省恶性疟流行状况及抗氯喹恶性疟的分布、发展及治疗方案。     

Synthesis of [2H]‐ and [13C]‐labeled pyronaridine tetraphosphate—an antimalarial drug

The increasing prevalence of strains of Plasmodium falciparum resistant to chloroquine and other antimalarial drugs, necessitates the need for developing novel antimalarial drugs with a potent pharmacological activity. Pyronaridine tetraphosphate (PNDP) is one such drug that is currently undergoing preclinical and clinical trials for use in a chemotherapy treatment of malaria. The present investigation was carried out with the objective of synthesizing carbon‐13 [¹³C]‐ and deuterium [²H]‐labeled PNDP for use in studying the ADME and pharmacokinetics of the drug. Here, we present a methodology to synthesize [¹³C]‐ and [²H]‐PNDP using a microwave irradiation technique as this method was found to be more advantageous than the classical method. The labeled compounds thus synthesized had a chemical purity of >99% as determined by HPLC and were also found to be relatively stable up to 3 months when stored under standard conditions. Further they also revealed satisfactory instrumental analysis data. Copyright © 2008 John Wiley & Sons, Ltd.     

Pyronaridine induces apoptosis in non-small cell lung cancer cells by upregulating death receptor 5 expression and inhibiting epidermal growth factor receptor

Lung cancer is the leading cause of cancer death. Pyronaridine, a synthetic drug of artemisinin, has been used in China for over 30 years for the treatment of malaria, but its effect on non-small cell lung cancer (NSCLC) cells is rarely reported. In this study, we determined the efficacy of pyronaridine in four different NSCLC cell lines and explored its mechanism in H1975. The data showed that pyronaridine could upregulate the expression of TNF-related apoptosis-inducing ligand (TRAIL)-mediated death receptor 5 to promote cellular apoptosis. Meanwhile, the JNK (c-Jun N-terminal kinase) level was detected to be significantly increased after treating with pyronaridine. We used JNK inhibitor and found that it could partially inhibit cell apoptosis. The results showed that epidermal growth factor receptor (EGFR), PI3K, and AKT were downregulated after the treatment of pyronaridine. In summary, pyronaridine can selectively kill NSCLC by regulating TRAIL-mediated apoptosis and downregulating the protein level of EGFR. It is a promising anticancer drug for NSCLC.     

中缅边境西段缅甸恶性疟原虫对氯喹、青蒿琥酯及咯萘啶的敏感性体外测定

应用Rieckmann体外微量法测得中缅边境西段缅甸境内感染的恶性疟原虫对氯喹及我国抗疟新药青蒿琥酯及咯萘啶的抗性率分别为100％、14.3％及19.0％,半数抑制量(ID_(50)依次为249.5、4.2及12.1nmol/L。3例抗青蒿琥酯恶性疟原虫对氯喹和咯萘啶的ID_(50)分别为335.6nmol/L和43.1nmol/L;4例抗咯萘啶恶性疟原虫对氯喹和青蒿琥酯的ID_(50)分别为260.1nmol/L和5.0nmol/L。结果显示抗青蒿琥酯恶性疟原虫对咯萘啶及氯喹有明显的交叉抗性;抗咯萘啶恶性疟原虫对青蒿琥酯无交叉抗性。当地恶性疟原虫对氯喹的抗性程度明显高于云南南部恶性疟原虫,但对其它2种药物的敏感性则无明显差别,提示当地恶性疟原虫对青蒿琥酯及咯萘啶无交叉抗性。     

磷酸咯萘啶治疗恶性疟疾140例临床疗效观察

应用国产磷酸咯萘啶治疗非洲桑给巴尔籍140例恶性反复发作性疟疾,应用4mg/kg 体重深部肌肉注射,6小时后复注一次。若48小时后疟原虫不转阴者再给药一次。观察退热时间及疟原虫转阴时间均显著短于30例应用氯喹治疗的对照组(P<0.001)。且对氯喹耐药虫株同样有效。治疗期间作用药前后ECG,肝功能及尿常规检查说明本品杀虫作用强、副作用少。     

抗药性疟疾的化疗

综述了７０年代以来抗疟药研究的进展，介绍了抗疟新药甲氟喹、青蒿素、青蒿琥酯、蒿甲醚、咯萘啶、卤泛群及配伍用药治疗抗氯喹恶性疟临床研究的基本概况。     

咯萘啶逆转人乳腺癌MCF-7/ADM细胞耐药性及机制探讨

目的 在明确咯萘啶(PND)逆转人乳腺癌细胞MCF-7/ADM耐药性的药效基础上,初步探索作用机制。方法采用MTT法检测单用阿霉素(ADM)和联用咯萘啶(PND)对人乳腺癌敏感细胞MCF-7和耐药细胞MCF-7/ADM的抑制作用,得出半数抑制浓度(IC₅₀),并计算耐药倍数和逆转倍数。Western blot检测细胞中Fas和Caspases-3蛋白表达。结果ADM对MCF-7和MCF-7/ADM的IC₅₀分别为1.399 μg/mL和43.885 μg/mL,耐药倍数为31.4倍。PND(0.5 μg/mL)联合ADM作用MCF-7/ADM的IC₅₀为3.246 μg/mL,逆转倍数为13.5倍,并能提高耐药MCF-7/ADM中Fas和Caspases-3蛋白表达。结论PND能够逆转人乳腺癌细胞MCF-7/ADM耐药性,通过上调膜蛋白Fas表达,增加MCF-7/ADM对ADM的敏感性,从而促进细胞凋亡。     

咯萘啶与磺胺多辛-乙胺嘧啶单剂及两天疗法加伯氨喹治疗恶性疟的效果

目的：在海南省多重抗性恶性疟流行区，观察咯萘啶加伯氨喹与磺胺多辛－乙胺嘧啶加伯氨喹两种方案治疗恶性疟的效果。方法：采用咯萘啶与磺胺多辛－乙胺嘧啶各５００ｍｇ、１０００ｍｇ、５０ｍｇ单剂口服以及３药各８００ｍｇ、１０００ｍｇ、５０ｍｇ２ｄ分服，同时各加伯氨喹４５ｍｇ２ｄ分服，治疗恶性疟各５０例。结果：平均退热时间分别为３９．８±２７．２ｈ和４２．１±２０．５ｈ，原虫无性体转阴时间分别为４６．９±１３．３ｈ和５１．０±１４．２ｈ，２４ｈ减虫率分别为８０％和７８％。２８ｄ治愈率皆为１００％。药物副反应较轻，一般不需特殊处理，但两组各有３例发生溶血反应，心电图有窦性心动过缓或伴窦性心律不齐。结论：表明两种方案均可治愈抗性恶性疟。     

双氢青蒿素与咯萘啶伍用治疗抗性恶性疟的研究

目的　寻找更理想的治疗抗药性恶性疟的联合用药方案。　方法　双氢青蒿素、咯萘啶单用及伍用分别治疗24、25和32例恶性疟现症患者,分别于服药后第14、21及28天随访,以退热时间、原虫消失时间、复燃时间、复燃率、治愈率、配子体携带率、药物副作用发生率等为指标,以双氢青蒿素、咯萘啶标准疗法为对照,进行临床双盲试验,综合评估双氢青蒿素合并咯萘啶疗法。　结果　伍用组退热时间35.7±24.7h与咯萘啶单用组35.8±16.5h相似(P>0.05),显著快于双氢青蒿素单用组52.6±38.9h(P<0.01)。伍用组无性体原虫消失时间23.8±10.1h与双氢青蒿素单用组22.9±6.5h相似(P>0.05),显著快于咯萘啶单用组49.4±20.3h(P<0.01)。伍用组治后配子体出现率、持续时间及密度分别为20.0%、5.7d和4个/μl血,与双氢青蒿素单用组16.7%、3.5d和3个/μl血相似(P>0.05),明显好于咯萘啶单用组60.9%、11.5d和12个/μl血(P<0.01)。3种方案均无明显药物副反应。　结论　双氢青蒿素与咯萘啶伍用保持了两药的优点,克服了两药的不足,是目前治疗抗性恶性疟较为理想的药物组合