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ED₅₀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(I₅₀=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ED₅₀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。     

2006—2013年菏泽市输入性恶性疟的临床特点与处置分析

目的探讨2006—2013年25例输入性恶性疟的流行特征及临床诊断和治疗效果。方法回顾性分析恶性疟病例的流行病学资料及临床资料。结果 25例恶性疟病例均有蚊虫叮咬史和有非洲地区居留史,临床症状主要为发热、畏寒、大汗、呕吐、贫血、血小板数减少、和肝肾功能异常等。在蒿甲醚联合伯氨喹治疗后,25例恶性疟均获痊愈,无输入性恶性疟传播。结论菏泽市输入性恶性疟以有非洲旅居史,青年、中年男性为主,近年来发病有所增加;恶性疟诊断主要依靠反复外周血涂片检测;蒿甲醚联合伯氨喹治疗方案治疗效果可靠。     

Compliance to recommendations for the management of curative treatment of Plasmodium vivax/ovale infections

Objectives

We assessed the compliance to recommendations for the routine management of Plasmodium vivax/ovale malaria, and analyzed the impact of discrepancies on the quality of care.

Patients and methods

We reviewed the cases of P. ovale and P. vivax malaria treated at the Besançon University Hospital, France (2008–2013).

Results

Chloroquine was prescribed in 44% of the 18 cases (4 due to P. ovale, 14 to P. vivax). Radical cure with primaquine was prescribed after the first bout of malaria for 6 patients. The primaquine dose prescribed was inferior to the recommended one for 4 patients. The mean delay between schizonticide treatment and primaquine cure was 43 days.

Conclusions

The delay before access to primaquine radical cure was the only parameter, likely to alter treatment effectiveness, but also difficult to shorten. Future national guidelines should take into account that not all patients have access to primaquine treatment immediately after schizonticide treatment.     

Extracellular Na+ removal attenuates rundown of the epithelial Na+-channel (ENaC) by reducing the rate of channel retrieval

Regulation of the epithelial sodium channel (ENaC) is important for the long-term control of arterial blood pressure as evidenced by gain of function mutations of ENaC causing Liddles syndrome, a rare form of hereditary arterial hypertension. In Xenopus laevis oocytes expressing ENaC a spontaneous decline of ENaC currents over time, so-called rundown, is commonly observed. Mechanisms involved in rundown may be physiologically relevant and may be related to feedback regulation of ENaC by intra- or extracellular Na⁺. We tested the effect of extracellular Na⁺ removal on ENaC rundown. Spontaneous rundown of ENaC was largely prevented by extracellular Na⁺ removal and was partially prevented by primaquine suggesting that it is due to endocytic channel retrieval. Liddles syndrome mutation caused a reduced rate of rundown, and in oocytes expressing the mutated channel extracellular Na⁺ removal not only prevented rundown but even increased the ENaC currents (runup). Acute exposure to high extracellular Na⁺ drastically reduced whole-cell currents and surface expression of wild-type ENaC, while these effects were much smaller in ENaC with Liddles syndrome mutation consistent with a stabilization of the mutated channel in the plasma membrane. Interestingly, the apparent intracellular Na⁺ concentration [Na⁺]_i-app was high (>60 mM) in ENaC-expressing oocytes but rundown was not associated with a further increase in [Na⁺]_i-app. We conclude that the inhibitory effect of extracellular Na⁺ removal on rundown is due to an inhibition of endocytic ENaC retrieval.     

Pharmacokinetics of primaquine and carboxyprimaquine in Korean patients with vivax malaria

Primaquine is used for relapses caused by vivax malaria hypnozoites. No studies on the pharmacokinetics of primaquine (PMQ) has been reported in Korean patients. In our study, thirty vivax malaria patients were given 15 mg primaquine daily for 14 days after 3 days of chloroquine treatment. Plasma samples were taken at intervals after each daily dose of PMQ for 3 days. Plasma concentrations of PMQ and carboxyprimaquine (CPMQ), the major metabolite of primaquine, were measured by HPLC. The PMQ concentrations reached a maximum of 0.28+/-0.18 microg/mL at 1.5 h after the first dose. The maximum concentration of CPMQ was 0.32+/-0.13 microg/mL at 4 h. Higher drug concentrations with repeated dosing were observed for CPMQ, but not for the parent drug, PMQ. The elimination half-life was 3.76+/-1.8 h and 15.7+/-12.2 h, for PMQ and CPMQ, respectively. Large variation in the plasma concentrations of both drugs was observed. Overall, PMQ is absorbed and metabolized rapidly after oral administration. It was noted that the mean peak plasma concentration of PMQ was significantly higher and that of CPMQ was lower in our patients compared to other studies. This suggests a potential difference of inter-ethnic groups, which warrants further investigations.     

辛酰伯喹在家兔体内的药代动力学研究

本文阐述了辛酰伯喹在家兔体内的药代动力学。应用最优化理论中的单纯形法自编计算机程序处理家兔静注辛酰伯喹丙二醇后的血药浓度-时间数据,拟合曲线以开放性三室模型描述较为适宜,其药代动力学参数为:T_(1/2)(λ_3、λ_2和λ_1相)3.410±1.394,0.5420±0.4373和0.1232±0.1045h;V_c 1.261±1.138 1/kg;Vd(ss)6.383±5.072 1/kg;Vd(λ_3)15.59±9.937 1/kg;AUC 9.108±3.793μg·h·ml~(-1);Cl_s 3.158±1.220 1·kg~(-1)·h~(-1);k_(10) 4.315±2.775h~(-1);k_(12)2.003±1.312h~(-1),k_(21) 2.373±0.7639h~(-1),k_(13) 1.127±0.9859h~(-1),k_(31) 0.3107±0.1158h~(-1)。     

疟原虫组织期裂殖体杀灭剂的研究:2-取代苄氧基(或甲氧基)-5-取代苯氧基-伯氨喹类似物的合成

本文报道了间日疟根治药伯氮喹2位引入取代苄氧基或甲氧基,5位引入取代苯氧基的类似物的合成。其中以化合物39及45对疟原虫组织期裂殖体的作用最强,约氏疟原虫子孢子感染的小鼠喂服100mg/kg单剂,分别有80%及90%的受试小鼠未查见原虫血症。化合物45降至20mg/kg单剂时,80%的受试小鼠也未出现原虫;对小鼠的急性毒性低于伯氨喹。     

青蒿琥酯联用伯氨喹治疗迁延、复燃疟疾的临床研究

目的:探讨青蒿琥酯联用伯氨喹治疗迁延、复燃疟疾的临床疗效。方法:将82例患者随机分成治疗组和对照组各41例。治疗组:给予青蒿琥酯和伯氨喹:青蒿琥酯首剂2.4 mg/kg i.v.,12 h后予1.2 mg/kg青蒿琥酯,随后6 d每日以1.2 mg/kg青蒿琥酯同法给予;同时加服伯氨喹片22.5 mg q.d.。对照组:给予quini max,首剂20 mg/kg,i.v.gtt,12 h后予10 mg/kg,随后每日12 h给予10 mg/kg,直至患者能口服,改口服quini max片10 mg/kg,q.8.h,疗程7 d。结果:7 d后治疗组、对照组治愈率分别为97.5%、95.1%;28 d治疗组、对照组治愈率分别为97.5%、90.2%,治疗组与对照组变化相近(P>0.05);两组的退热时间分别为28.0、51.6 h,血中疟原虫清除时间分别为30.4、59.5 h,治疗组较对照组均降低(P<0.01)。结论:青蒿琥酯联用伯氨喹治疗疟疾作用迅速,副作用小,低复燃率,且对耐奎宁株有效,可作为迁延、复发疟疾以及用奎宁等传统抗疟药治疗失败的首选方法。