吡喹酮与左旋吡喹酮治疗华支睾吸虫病的对比观察

1972年吡喹酮问世,很快成为治疗血吸虫病、华支睾吸虫病、肺吸虫病首选药。吡喹酮是左、右旋各半组成的外消旋化合物,重庆医科大学化学教研室拆分合成吡喹酮的中间体而获得左旋吡喹酮和右旋吡喹酮二种光学异构体。左旋吡喹酮治疗血吸虫病疗效优于吡喹酮,而右旋吡喹酮杀血吸虫作用甚微因此,我们用吡喹酮及两种光学异构体进行了大鼠实验治疗以及在现场采用左旋吡喹酮与毗喹酮治疗华支睾吸虫病进行对比观察其疗效,现将结果报告如下。     

蛋白激酶C及其亚型对钙通道的调节功能

吡喹酮是目前治疗血吸虫的惟一特效药,但其作用靶点及机制仍未完全阐明,研究表明吡喹酮的作用靶点町能为钙通道.钙通道可受多种因素的调控,该文综述了蛋白激酶C及其亚型对钙通道的调控作用,为阐明吡喹酮的药物作用机制以及进一步研发抗血吸虫新药提供了思路.     

吡喹酮的免疫依赖性与免疫协同性

吡喹酮是一种广谱抗蠕虫药,它的抗虫作用具有免疫依赖性和免疫协同性。该文概述了其免疫依赖性和免疫协同性的发现过程及有关证据,推断了其作用机制,介绍了吡喹酮与一些免疫因子抗日本血吸虫的协同作用以及吡喹酮抗虫治疗对宿主免疫功能的影响,并提出了需要继续探讨的问题。     

大鼠及犬皮下埋植吡喹酮控释棒的药物释放及预防细粒棘球蚴原头节感染的初步观察

报告了一种吡喹酮控释棒，并实验观察了这种用于皮下埋植的吡喹酮缓释制剂在大鼠和家犬体内的缓释效果和对家犬细粒棘球绦虫成虫感染的驱虫作用。初步观察结果，在大鼠体内６０天的药物释放率为４７．６％；在家犬体内７５天的释放率为５２．３％。在实验犬体内吡喹酮埋植量为３２．９３～６５．８８ｍｇ／ｋｇ的情况下，有明显的驱虫作用     

吡喹酮治疗血吸虫病肝纤维化的实验研究

目的观察吡喹酮对血吸虫病肝纤维化的治疗作用。方法将小鼠随机分为正常对照组、模型组、吡喹酮组。模型组、吡喹酮组小鼠经腹部皮肤感染日本血吸虫尾蚴诱导肝纤维化模型,吡喹酮组于感染8周后灌胃吡喹酮治疗2次。16周末测小鼠血清中ALT、AST;观察小鼠肝脏形态,HE染色观察肝纤维化病理组织变化,测定虫卵肉芽肿面积;免疫组化测定肝脏Ⅰ和Ⅲ型胶原表达。结果吡喹酮治疗可降低血吸虫病肝纤维化小鼠肝脏指数及血清ALT、AST,改善肝组织形态结构,降低肝脏Ⅰ和Ⅲ型胶原表达及虫卵肉芽肿面积。结论吡喹酮对血吸虫病肝纤维化有明显治疗作用。     

血吸虫钙调蛋白与吡喹酮杀虫作用机理

提取了日本血吸虫成虫之钙调蛋白制成 DNS—虫钙调蛋白,利用它本身的荧光及加入荧光探针,观察了吡喹酮对其蛋白构象的影响,从而表明在钙离子存在下吡喹酮可与虫钙调蛋白发生结合。对动物钙调蛋白具有亲和性的三氟拉嗪、氯丙嗪及异博定等在体外具有吡喹酮相似的杀虫效果,但在小鼠体内的效果较差。作者认为吡喹酮的杀虫作用是由于吡喹酮使血吸虫的钙调蛋白构象发生固定化,从而导致了一系列代谢系统失调的结果。     

大鼠及犬皮下埋植吡喹酮控释棒的药物释放及预防细粒棘球蚴原头节感 …

报告了一种吡喹酮控释棒，并实验观察了这种用于皮下埋植的吡喹酮缓释制剂在大鼠和家犬体内的缓释效果和对家犬细粒棘球绦虫成虫感染的驱虫作用。初步观察结果，在大鼠体内６０天的药物释放率为４７．６％，在家犬体内７５天的释放率为５２．３％。在实验犬体内吡喹酮埋植量为３２．９３￣６５．８８ｍｇ／ｋｇ的情况下，有明显的驱虫作用。     

抗包虫药物的实验研究——Ⅰ.吡喹酮体外抗细粒棘球蚴原头节的作用

在20％小牛血清-RPMI1640中,吡喹酮对体外培养的细粒棘球蚴原头节有较强的杀灭作用,主要表现为外翻、皮层肿胀、泡状物形成、破裂,以及头钩排列紊乱和脱落等,24h后即出现死亡,3天内的死亡率达90％以上。吡喹酮对培养在囊液中的原头节亦有杀灭作用,但对培养在RPMI1640和HBSS中的则无。进一步观察的结果表明,吡喹酮在体外抗原头节的作用需赖于有蛋白质的存在。此外,小鼠口服吡喹酮后,其血清有抗原头节作用,主要成份为吡喹酮原药。     

吡喹酮激惹对日本血吸虫病人血清循环抗原水平的影响

本文报道了吡喹酮对日本血吸虫病人血清循环抗原(CAg)的激升效应。病人分别在经40mg、20mg、10mg/kg 体重剂量的吡喹酮作用后1、3、6天以单克隆抗体 Dot-ELISA(McAb-Dot-ELISA)检测血清循环抗原,结果显示,其检出水平显著高于吡喹酮作用前,平均检出滴度提高1～4倍,阴性样本经吡喹酮激惹后均转为阳性。此结果提示,在经吡喹酮激惹后短时间内,病人血清的 CAg 水平有一个明显的升高过程,此举对于提高慢性、低感染度血吸虫病人的血清 CAg 检出水平具有一定的意义。     

吡喹酮抗肝纤维化作用研究进展

吡喹酮除具有广谱抗吸虫和绦虫作用外,还具有调节炎症反应、抗纤维化等药理作用。本文综述了吡喹酮抗肝纤维化作用及其机制,以期为吡喹酮用于肝纤维化治疗提供理论依据。 =     

Effectiveness of different approaches to mass delivery of praziquantel among school-aged children in rural communities in Nigeria

Schistosomiasis is hyperendemic in Nigeria. The national policy on schistosomiasis control has adopted praziquantel as the main drug of use in the control strategy aimed at reducing morbidity. However, the best delivery channel for praziquantel in schistosomiasis control in Nigeria is yet to be determined. This study assessed different channels for praziquantel delivery in a mass treatment effort. Three groups, each of two communities, were assigned to one of the following three channels: health facility (HF), school, and community for mass delivery of praziquantel to school-aged children. Distributors were trained on all aspects of praziquantel distribution and sufficient praziquantel tablets were provided for the drug distribution within 3 weeks following which an evaluation of the drug distribution by the different treatment channels was conducted. Overall, the community channel of delivery achieved the best coverage of 72.2% (range: 69-73%) compared to 44.3% (range: 39.5-62%) and 28.5% (range: 26.3-74.5%) for the HF and school channels, respectively. Community channel of praziquantel delivery as shown in this study ensures good coverage of both in and out-of-school children.     

Use of praziquantel for clinical treatment and morbidity control of schistosomiasis japonica in China: a review of 30 years' experience

Chemotherapy is widely acknowledged as the most important, rapid and cost-effective method of reducing morbidity due to schistosome infections. The discovery of praziquantel in the 1970s has been a breakthrough for treatment of patients infected with schistosomes, including Schistosoma japonicum in China, and entire communities at risk of schistosomiasis. Praziquantel is usually administered in a single oral dose and has no or only mild and transient side effects. The drug is highly efficacious against S. japonicum, both in patients with acute and chronic stages of the infection, among subjects with extensive hepatosplenic involvement, and in patients with other complicated diseases. The cost of praziquantel has been reduced significantly over the past years. Hence, praziquantel has become the backbone of the national schistosomiasis control programme in China and in other countries where the disease remains endemic, most notably in sub-Saharan Africa. Chemotherapy with praziquantel also plays a role in transmission control of schistosomiasis, although transmission interruption cannot be reached by chemotherapy alone. Here, I review 30 years' of experiences gained with the use of praziquantel for clinical treatment and larger-scale control of schistosomiasis japonica in China.     

钙通道β亚单位相关作用蛋白ahnak的研究进展

吡喹酮作为当前治疗血吸虫病的首选药物,对所有种类的血吸虫均有疗效且副作用甚微,临床应用已达30余年,但其作用机制至今尚未完全阐明.研究表明吡喹酮抗血吸虫作用与Ca~(2+)内稳态的破坏有直接关系.电压门控性钙通道(voltage-gated calcium channels,VGCC)为Ca~(2+)的内流提供通道,并已有研究者提出了"血吸虫钙通道-吡喹酮作用靶点"假说.研究显示ahnak蛋白与钙通道β亚单位结合能增加Ca~(2+)内流,该文围绕ahnak蛋白的基本结构、功能以及ahnak/β亚单位之间的相互作用及功能等方面的研究进展作一综述,为探讨吡喹酮抗血吸虫的机制提供一定的参考价值.     

吡喹酮引起药物热1例

本文报道服吡喹酮后出现药物热1例。     

Exudative polyserositis and acute respiratory failure following praziquantel therapy

Praziquantel is recommended as the drug of choice for all forms of schistosomiasis. We report the first case (to our knowledge) of exudative effusive polyserositis following treatment of schistosomiasis with this drug. This involved pleura, pericardium, and peritoneum and was associated with acute respiratory failure. The latter preceded the appearance of pleural effusions. We present a brief review of the literature and attract attention to the need for close observation of patients with schistosomiasis who are treated with praziquantel.     

Comparison between the efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infections on a sugar estate in Ethiopia

The efficacy of the antischistosomal drugs praziquantel and oxamniquine was tested on four groups of Ethiopian sugar estate workers. The cure rates, determined by the absence of eggs in stools, were 96, 93 and 74% at one, three and six months post-treatment for patients receiving a single dose (40 mg kg-1 body weight) of praziquantel, and 82, 78 and 78% for patients on a single dose (15 mg kg-1 body weight) of oxamniquine. When split doses of these drugs were used, praziquantel achieved cure rates of 96, 95 and 89%, while the corresponding cure rates for oxamniquine were 98, 96 and 88% at one, three and six months post-treatment. In general, there were no statistically significant differences within the single and split doses of each drug, nor between the two drugs except that single doses of praziquantel had significantly higher cure rates than oxamniquine at one and three months post-treatment. Although both drugs produced mild and transient side-effects such as dizziness, abdominal discomfort and diarrhoea, serious side-effects such as seizures were seen only among patients on oxamniquine. As praziquantel is also effective against other forms of schistosomiasis as well as against cestodes, we recommended the use of this drug in mass chemotherapy and in the ambulatory treatment of schistosomiasis in Ethiopia.     

脑型血吸虫病的手术治疗

回顾性分析手术治疗48例脑型血吸虫病患者的临床资料,对CT证实病灶较大、占位效应明显、有明显颅高压症状、药物治疗无效或不能完全排除胶质瘤的患者,采取手术治疗,病情稳定后按常规口服吡喹酮治疗。48例中,术后恢复良好35例,肢体瘫痪加重8例,肢体麻木加重5例,新出现癫痫发作2例,无手术死亡。提示手术结合药物治疗脑型血吸虫病可获良好疗效。     

A safe, effective, herbal antischistosomal therapy derived from myrrh.

Schistosomiasis is a widespread helminthic disease. Treatment of schistosomiasis is based on chemotherapy with praziquantel, which is the drug of choice. Since resistance to praziquantel has been demonstrated, alternative drugs must be considered. Myrrh is an oleo-gum resin from the stem of the plant Commiphora molmol. This study was carried out on 204 patients with schistosomiasis. The drug was given at a dose of 10 mg/kg of body weight/day for three days, and induced a cure rate of 91.7%. Re-treatment of cases who did not respond with a dose of 10 mg/kg of body weight/day for six days gave a cure rate of 76.5%, increasing the overall cure rate to 98.09%. The drug was well tolerated, and side effects were mild and transient. Twenty cases provided biopsy specimens six months after treatment and none of them showed living ova.     

Praziquantel: is there real resistance and are there alternatives?

The low cure rates obtained with praziquantel in a Senegalese focus of schistosomiasis can best be interpreted on the basis of epidemiological factors, and are unlikely to be connected with any drug resistance in the parasite. Schistosome isolates obtained in Egypt from uncured patients present evidence of lower susceptibility to the drug, albeit to a rather limited extent. Similarly, laboratory schistosomes subjected to repeated passages under drug pressure are partly insensitive to the drug. Oxamniquine is at present the only available alternative to praziquantel. Research and development of new antischistosomal drugs is urgently needed.