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1.
锥虫抗药性机制的研究进展 总被引：1，自引：0，他引：1
为了较全面地了解锥虫抗药性机制的研究进展,综述了国内外有关报道。锥虫抗药性形成的机制主要表现在三方面,即锥虫体内酶的活性（或含量）发生变化,抗药株虫体的苹果酸酶、锥虫硫酮还原酶或鸟氨酸脱羧酶等酶的活性明显升高;锥虫细胞膜上的特异载体,即细胞膜上转运腺苷酸和腺苷的Ｐ２载体发生改变,药物进入虫体受阻;虫体的抗药基因被激活或基因发生重组、突变或扩增。本文还总结了锥虫抗药性机制研究中存在的问题及今后的研究 相似文献
2.
为了探讨伊氏锥虫对安锥赛抗药性的分子基础，将伊氏锥虫单虫克隆，一部分克隆虫通过28只免疫抑制小白鼠，用安锥赛亚治疗剂量治疗，使其产生抗药性，为抗药锥虫；另一部分克隆锥虫也通过28只免疫抑制小白鼠,，但不用药物治疗，为敏感锥虫，即对照，用体外生长抑制法测得抗药和敏感锥虫的IC50分别为43．8和0．16878μg/ml。分别提取它们的总RNA和mRNA，总RNA分离出3条带，即从电泳的阴极到阳棚分别为26s,21s和5s,mRNA主要分布在21sRNA之后。用抑制性消减杂交法，以敏感锥虫的cDNA为试验组（Tester)，抗药锥虫的cDNA为驱动组（Driver)，共挑选出34个阳性克隆，以cDNA来合成探针，用Southern dot blot鉴定，其中18个片段所在的基因是由于抗药性产生而表达量降低，这18个片段长度为300－700bp。 相似文献
3.
锥虫不同抗原免疫学特性研究进展杨发青孙恩贵刘俊华王祥生（解放军农牧大学军事兽医研究所·长春·１３００６２病源性锥虫对人类的健康和农牧业生产存在相当大的危害。化学药物防治往往由于抗药性、毒副作用大或杀伤力低而难以达到理想的效果，［１］加之虫体变异和对媒... 相似文献
4.
《中国动物传染病学报》2016,(6)
为检测实验室长期保存的柔嫩艾美耳球虫马杜拉霉素抗药株和地克珠利抗药株的遗传稳定性,采用鸡体试验法,以抗球虫指数、最适抗球虫活性百分率、病变记分减少率和相对卵囊产量4项指标,评价2个抗药株对地克珠利、癸氧喹酯、马杜拉霉素等3种抗球虫药物的抗药性,并以柔嫩艾美耳球虫敏感株为对照。结果显示,柔嫩艾美耳球虫敏感株对3种抗球虫药物均无抗药性,4项指标全部阴性。柔嫩艾美耳球虫马杜拉霉素抗药株对马杜拉霉素为完全耐药,4项指标全部阳性;对地克珠利、癸氧喹酯则表现为无抗药性,4项指标全部阴性。柔嫩艾美耳球虫地克珠利抗药株对地克珠利表现为完全耐药,4项指标全部阳性;对马杜拉霉素表现为中度耐药,2项指标阳性;对癸氧喹酯则表现为无抗药性,4项指标全部阴性。结果表明,在实验室已繁殖保存10余年的柔嫩艾美耳球虫2个抗药虫株对其诱导药物具有明显抗药性,实验室保种繁殖方法可行,虫株遗传稳定性良好,为利用该虫株进行球虫抗药性机制等相关研究奠定了基础。 相似文献
5.
伊氏锥虫对安锥赛抗药性机制的初步探讨 总被引：1，自引：0，他引：1
选用克隆伊氏锥虫的安锥赛敏感株 C0 1、C0 3和 5个不同程度抗药株 C1、C2、C4、C6、C7,用聚丙烯酰胺凝胶电泳分离它们的己糖激酶 (HK)、6 -磷酸葡萄糖脱氢酶 (G6 PDH)、丙氨酸转氨酶 (AL AT)、天冬氨酸转氨酶 (ASAT)同功酶 ,并测定胆碱酯酶活性。结果 ,这 5种酶与伊氏锥虫对安锥赛产生抗药性无关。用 SDS-聚丙烯酰胺凝胶电泳分离和测定这 7个样品的粗蛋白质 ,结果相对分子质量为 15 790带在抗药株 C1、C2、C4、C6和 C7含量较高 ,这表明它可能与安锥赛抗药性的产生有一定关系 ;相对分子质量为 1976 0带在高抗药株 C4、C6和 C7的含量很高 ,这表明它可能也与抗药性的产生有一定关系 相似文献
6.
病原体的药物抗性是日益严重的问题，其机制尚不完全了解。一般认为细胞摄入抗布氏锥虫的药大多是通过一种至今尚未被识别的不平常的腺苷运输系统发生的，使用酿酒酵母（Ｓａｃｃｈａｒｏｍｙｃｅｓ ｃｅｒｅｖｉｓｉａｅ）以功能筛选的方法克隆了布氏锥虫指名亚种（Ｔｒｙｐａｎｏｓｏｍａ ｂｒｕｃｅｉ ｂｒｕｃｅｉ）的一个编码核苷酸运输系统的基因－ＴｂＡＴ１。ＴｂＡＴ１在酵母中表达时，使酵母能摄取腺苷，并赋予对密胺基苯胂类药物（Ｍｅｌａｍｉｎｏｐｈｅｎｙｌ ａｒｓｅｎｉｃａｌｓ）的敏感性，抗药锥虫藏匿缺损ＴｂＡＴ１的变种，杀锥虫药进入细胞途径的分子识别开辟了诊断和治疗抗药锥虫病的途径。 相似文献
7.
克隆伊氏锥虫对安锥赛抗药性的培育 总被引：2，自引：1，他引：1
为了深入观察伊氏锥虫对安锥赛抗药性的形成,将伊氏锥虫浙江水牛株克隆,克隆繁殖后的虫体一部分作为原种对照组,即C01组;一部分虫体连续经环磷酰胺免疫抑制的小鼠,再用安锥赛亚治疗剂量治疗该小鼠,使其伊氏锥虫对安锥赛产生7个不同程度的抗药性组,即C1～C7组;另一部分虫体也连续经环磷酰胺免疫抑制的小鼠,作为伴随C7的同步繁殖组,即不用药物的C02组.结果C01、C02、C1～C7组所用安锥赛剂量依次为0、0、6、16、40、80、196、406、638mg/kg,它们经小鼠传代数依次为0、28、1、3、6、9、15、22、28代.用体外生长繁殖抑制法测得它们的ICs0值依次为0.015 50、0.016 87、0.082 60、0.102 37、1.409 29、1.922 90、9.923 30、23.563 00、43.84000.结果表明,安锥赛亚治疗剂量与伊氏锥虫抗药性的IC50值呈曲线关系,从C1到C4的IC50值上升较缓慢,从C4后的ICs0值上升较快,并且几乎呈直线上升;伊氏锥虫所经小鼠的代数与它们的IC50值的关系呈抛物线型,从C1到C4的ICs0值上升很慢,C4以后的IC50值上升很快.用体内试验测试C01～C4组的CD100值,每个组感染35只小鼠,每只小鼠接种1.0×104条锥虫,其中30只小鼠分为安锥赛的3个剂量治疗小组,另5只小鼠为不治疗对照组.结果C01组和C1组的CD100值分别为7.0、13.0 mg/kg,这表明C1组只经1代免疫抑制小鼠,注射安锥赛剂量3×2 mg/kg,就使该组伊氏锥虫对安锥赛的抗药性提高了6 mg/kg,并且它们的IC50值C1是C01的6.6倍.C2、C3和C4组由于抗药性程度过高均不能治愈,因此尚未测到它们的CD100值.这些结果表明,伊氏锥虫经免疫抑制小鼠对安锥赛产生抗药性的速度是非常快的. 相似文献
8.
鸡体内用5mg/kg马杜霉素作用于柔嫩艾美耳球虫（Eimeria tenella)敏感虫株和抗药虫株，比较裂殖生殖阶段超微结构的差异。敏感株型裂殖体体积变小，所生成裂殖子的数目变小，裂殖子膨胀，裂殖子间（带虫空泡内）微管膨胀，结构模糊，有髓鞘样结构出现；限制膜外突和细胞质分离形成空隙，膜结构模糊，有破损；细胞浆空泡化，出现附加体和髓鞘样结构；少数细胞核的外膜外突和内膜分离，有的部位的核膜模糊、破损。首次发现裂殖子顶体结构发生异常变化，棒状体消失，微线数目减少或者消失；线粒体表现为形态改变，嵴脱落，内部形成空泡、膜状结构和髓鞘样结构，线粒体的嵴与长辆平行排列，且贯穿线粒体。抗药虫株没有发现异常变化。推理抗生素类抗球虫药的作用机理为破坏虫体结构和抑制虫体的生理机能两个方面；球虫对该类药物产生抗药性的机制是基因突变和药物选择的结果。 相似文献
9.
现代驱虫药物的作用机理及其应用 《畜牧与饲料科学》1995,16(1):11-11
本文介绍了常用的新型广谱驱虫药物的作用机理及其适用范围,目的是通过对这些药物的驱虫机理以及对虫体作用位点的了解,能够合理地选用之,避免抗药性的产生,充分发挥药物的驱虫效力。 相似文献
10.
为探讨伊氏锥虫对安锥赛抗药性的分子机理,以已报导的布氏锥虫对砷剂药物抗药性相关的TbTA1基因设计引物,以不同退火温度(55℃、57℃、60℃、63℃和65℃)和不同DNA聚合酶(Clontech的50×Advantage Poly-merase Mix和上海生物工程公司的Taq聚合酶),分别从伊氏锥虫敏感株(C03)的cDNA和基因组DNA中分离出TbTA1基因的全长序列,而从抗药株(C7)的cDNA和基因组DNA中都没分离出TbTA1基因,这表明抗药株的Tb-TA1已发生改变;根据TbTA1的5'端和1041端设计引物,从敏感株和抗药株都分离到约1000bp的片段,这表明因安锥赛抗药性的产生而TbTA1的改变主要发生在TbTA1的1042-1415部分.由此确定TbTA1与伊氏锥虫的安锥赛抗药性有关.将伊氏锥虫敏感株的TbTA1克隆、测序,其序列与布氏锥虫TbTA1序列比较,它们有10个碱基不同,即第88位的G(T.e)-A(T.b)、第144位的T(T.e)-C(T.b)、第224位的C(T.e)-T(T.b)、第471位的C(T.e)-T(T.b)、第472位的A(T.e)-G(T.b)、第549位的G(T.e)-T(T.b)、第1008位的C(T.e)-T(T.b)、第1033位的A(T.e)-G(T.b)、第1293位的A(T.e)-G(T.b)和第1384位的T(T.e)-C(T.b),其中有5个碱基所编码的氨基酸不同,即Val30(T.e)-Ile(T.b)、Ala75(T.e)-Val(T.b)、Ile158(T.e)-Val(T.b)、Thr345(T.e)-Ala(T.b)和Ser462(T.e)-Pro(T.b),这表明伊氏锥虫与布氏锥虫的TbTA1差异可能是它们的种间差异. 相似文献
11.
Resistance to arsenical drugs in trypanosomes has been linked to changes in adenosine uptake. The transport of melaminophenyl arsenicals into Trypanosoma brucei was shown to be mediated by an unusual adenosine nucleoside transporter, P2 (Carter and Fairlamb, 1993), and the loss of this transporter is associated with resistance to melaminophenyl arsenicals in these parasites. To further understand the mechanisms of arsenical resistance, we generated several lines of Mel Cy-resistant T. evansi from a drug-sensitive isolate using both in vivo and in vitro selection methods. Uptake of the melaminophenyl arsenical, Mel Cy on the P2 transporter was studied in the drug-sensitive as well as Mel Cy-resistant parasites, by means of inhibition of Mel Cy-induced lysis of trypanosomes, in an in vitro lysis assay. Adenosine uptake was also investigated using competition inhibition assays.Our study shows that T. evansi, TREU 1840, possesses the P1/P2 adenosine transport system as reported in T. brucei and T. equiperdum. However, in T. evansi, the P2 transporter is the larger transport process instead of the P1. The P2 transporter in T. evansi mediated the uptake of Mel Cy in the drug-sensitive parasites. The P2 was retained in all the arsenical-resistant T. evansi lines studied. However, the activity of the transporter was reduced to different extents in the different-resistant lines. The residual P2 activity related well to the levels of drug resistance in each line, suggesting that P2 activity could be an important marker for arsenical resistance. Furthermore, important differences were observed between the in vivo- and the in vitro-selected arsenical-resistant parasites suggesting that there may be differences in resistance phenotypes selected on the field. 相似文献
12.
Both acquired and innate resistance to African trypanosomiasis can occur in cattle. The former raises the possibility of a vaccine against tsetsetransmitted metacyclic trypanosomes which have been shown to have a smaller repertoire of variable antigens than bloodstream parasites. The latter provides two further avenues of approach: firstly, trypanotolerant breeds are being increasingly exploited and improved by conventional management and breeding methods including embryo transfer; secondly, research is being carried out into the factors associated with their innate resistance, i.e., the control of trypanosome growth, the development of effective immune responses and resistance to anaemia. If the mechanisms underlying these factors are identified it might be possible by immunisation, by specific drug treatment or by transfection of appropriate genes to produce highly productive cattle resistant to trypanosomiasis. 相似文献
13.
Tsetse-transmitted livestock trypanosomosis affects livestock in large parts of sub-Saharan Africa. In southern Africa two epidemiological situations can be distinguished. The disease can have an endemic nature with high morbidity and low mortality in the livestock population. Endemic livestock trypanosomosis is found mainly in areas where cattle constitute the main host of tsetse and reservoirs of trypanosomes. Epidemic trypanosomosis, with high morbidity and high mortality is found in areas where wildlife persist as main reservoir and where livestock come into contact with tsetse flies transmitting trypanosomes from the sylvatic reservoir. Based on the differences in impact of the disease on livestock health in these two epidemiological settings, the appropriateness of the available trypanosomosis control tools differs. In trypanosomosis endemic areas, trypanocidal drug use could be the most suitable approach. Possible problems associated with the development of resistance in trypanosomes to the drugs need to be investigated further. In epidemic situations, vector control seems the most appropriate long-term solution. 相似文献
14.
Isometamidium chloride (Samorin, RMB, England) is a widely used and highly effective trypanocide for the treatment of bovine trypanosomiases. However, the appearance of isometamidium-resistant populations of T. congolense in Africa makes it necessary to develop methods for the rapid and reliable detection of drug resistance in the laboratory. Currently available tests are time-consuming and/or expensive. In the present study, the short-term in vitro incubation of trypanosomes in a range of isometamidium concentrations and the infectivity of the parasites in mice has been assessed. A series of T. congolense isolates were used which were known to differ in their in vivo sensitivity to the drug. The results showed a close correlation between the known level of resistance and the capability of trypanosomes to remain infective after incubation in isometamidium. Thus isolates displaying a high level of resistance in vivo remained infective following incubation in higher concentrations of drug. This assay may provide a simple and reliable method for detecting drug resistance in T. congolense. 相似文献
15.
In the last decade, there has been a wide range of studies using a series of molecular markers to investigate the genotypic diversity of some of the important species of African trypanosomes. Here, we review this work and provide an update of our current understanding of the mechanisms that generate this diversity based on population genetic analysis. In parallel with field based studies, our knowledge of the key features of the system of genetic exchange in Trypanosoma brucei, based on laboratory analysis, has reached the point at which this system can be used as a tool to determine the genetic basis of a phenotype. In this context, we have outlined our current knowledge of the basis for phenotypic variation among strains of trypanosomes, and highlight that this is a relatively under researched area, except for work on drug resistance. There is clear evidence for ‘strain’-specific variation in tsetse transmission, a range of virulence/pathogenesis phenotypes and the ability to cross the blood brain barrier. The potential for using genetic analysis to dissect these phenotypes is illustrated by the recent work defining a locus determining organomegaly for T. brucei. When these results are considered in relation to the body of research on the variability of the host response to infection, it is clear that there is a need to integrate the study of host and parasite diversity in relation to understanding infection outcome. 相似文献
16.
17.
Trypanosomes in the lymph nodes of cattle and sheep infected with Trypanosoma congolense 总被引：2，自引：0，他引：2
The prefemoral lymph nodes of two calves and a sheep infected with a stock of Trypanosoma congolense transmitted by Glossina morsitans were examined histologically for the presence of trypanosomes. Ten days after infection trypanosomes were found in the subcapsular sinuses of the nodes of a calf and the sheep but parasites were absent from the blood at this time. Trypanosomes were also detected in the prefemeral lymph node of the other calf on examination 30 days after infection, when parasites were also present in the blood. These observations provide further evidence that extravascular foci of trypanosomes develop in infections with T congolense and indicate that it should not be regarded as a strict plasma parasite. 相似文献
18.
Localised skin reactions (chancres) occurred on the flanks of cattle at the sites of deposition by tsetse flies of metacyclic forms of Trypanosoma congolense. Marked enlargement of the draining prefemoral lymph nodes accompanied the development of the skin reactions. Lymph from these nodes was collected through polyethylene cannulae inserted into the efferent lymphatics, and examined for trypanosomes, cells and antibody content. Within 6-9 days after infected tsetse fly bite, trypanosomes were detected in the efferent lymph; this preceded their appearance in the blood by 3-6 days, indicating that the lymphatic system acted as a major route for the passage of trypanosomes from the skin into the bloodstream. Responses induced in the draining lymph node as a result of trypanosome migration included a 2-3-fold increase in the volume of lymph and up to a 10-fold increase in lymphocyte output, including blast lymphocytes and plasma cells. Neutralising antibodies to metacyclic trypanosomes were detected in lymph and serum by Day 14 after infection, although in 2 out of 4 animals investigated, they were not demonstrated in serum until Day 18. Trypanosomes were also found in small numbers in efferent lymph of the prefemoral lymph node on the flank contralateral to the infected tsetse bites after development of parasitaemia. Increases in lymph flow and cellular output occurred about the same time in the ipsilateral and the contralateral efferent lymphatics, but were significantly less in the latter. Homologous challenge of immunised calves with tsetse-transmitted parasites revealed that trypanosomes were eliminated at the level of the skin or within the draining lymph node, as no parasites were detected in efferent lymph. 相似文献
19.
African trypanosomosis: from immune escape and immunopathology to immune intervention 总被引：2，自引：0，他引：2
Stijlemans B Guilliams M Raes G Beschin A Magez S De Baetselier P 《Veterinary parasitology》2007,148(1):3-13
African trypanosomes can cause prolonged chronic infections through a mechanism of antigen variation whereby they manipulate the humoral immune system of their hosts. However, besides antigenic variation these extracellular parasites exert other immunoregulatory activities mainly mediated by innate cells in particular macrophage-like (M) cells. In this review, the modulation of M cells through parasite factors and host cytokines as well as their role in parasite control and immunopathology will be examined. The concept of M cell polarization into distinct activation states (M1, M2) that may contribute to trypanosusceptibility or resistance will be discussed. Finally, the possibility to interfere with such activation states hereby providing new therapeutical modalities in the treatment of this infectious disease will be illustrated. 相似文献