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基因芯片技术在人体锥虫生物学特性研究方面的进展 被引量:6
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作者 陈木新 陈家旭 《中国寄生虫学与寄生虫病杂志》 CAS CSCD 北大核心 2016年第4期377-381,共5页
随着分子生物学技术的迅速发展,基因芯片技术在生物学和医学领域,以其高通量的特点展示出强大的优势。在众多人体血液原虫疾病中,锥虫病一直是国际关注的焦点,基因芯片技术为锥虫基因组、虫体与宿主的相互作用的研究,以及疫苗的筛选和... 随着分子生物学技术的迅速发展,基因芯片技术在生物学和医学领域,以其高通量的特点展示出强大的优势。在众多人体血液原虫疾病中,锥虫病一直是国际关注的焦点,基因芯片技术为锥虫基因组、虫体与宿主的相互作用的研究,以及疫苗的筛选和药物的研制提供了技术手段。本文就基因芯片在人体布氏锥虫(Trypanosoma brucei)和克氏锥虫(T.cruzi)研究中的应用作一概述。 展开更多
关键词 基因芯片 人体锥虫病 布氏锥虫 克氏锥虫
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美洲锥虫病的研究现状 被引量:4
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作者 王瑾 王宣焯 +1 位作者 郭中敏 陆家海 《传染病信息》 2018年第5期466-470,共5页
美洲锥虫病是由克氏锥虫引起的人兽共患病,又称为查加斯病。据估计全球目前约有1000万人感染美洲锥虫病,病例大多位于拉丁美洲,是最为普遍的"被忽视的热带病"之一。随着人口迁移和经济全球化的进程,该病已扩散至欧洲等区域,... 美洲锥虫病是由克氏锥虫引起的人兽共患病,又称为查加斯病。据估计全球目前约有1000万人感染美洲锥虫病,病例大多位于拉丁美洲,是最为普遍的"被忽视的热带病"之一。随着人口迁移和经济全球化的进程,该病已扩散至欧洲等区域,呈世界性流行趋势。我国目前尚无该病报道,但国内已发现其传播媒介即锥蝽,因此应受到人们的重视。 展开更多
关键词 美洲锥虫病 克氏锥虫 流行病学 临床表现 诊断 预防
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Modulation of immune response in experimental Chagas disease 被引量:1
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作者 Beatriz Basso 《World Journal of Experimental Medicine》 2013年第1期1-10,共10页
Trypanosoma cruzi(T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance i... Trypanosoma cruzi(T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance in the host, the amastigote, intracellular replicating form, and the extracellular trypomastigote, the infective form. Thus infection by T. cruzi induces a complex immune response that involves effectors and regulatory mechanisms. That is why control of the infection requires a strong humoral and cellular immune response; hence, the outcome of host-parasite interaction in the early stages of infection is extremely important. A critical event during this period of the infection is innate immune response, in which the macrophage's role is vital. Thus, after being phagocytized, the parasite is able to develop intracellularly; however, during later periods, these cells induce its elimination by means of toxic metabolites. In turn, as the infection progresses, adaptive immune response mechanisms are triggered through the TH1 and TH2 responses. Finally, T. cruzi, like other protozoa such as Leishmania and Toxoplasma, have numerous evasive mechanisms to the immune response that make it possible to spread around the host. In our Laboratory we have developed a vaccination model in mice with Trypanosoma rangeli, nonpathogenic to humans, which modulates the immune response to infection by T. cruzi, thus protecting them. Vaccinated animals showed an important innate response(modulation of NO and other metabolites, cytokines, activation of macrophages), a strong adaptive cellular response and significant increase in specific antibodies. The modulation caused early elimination of the parasites, low parasitaemia, the absence of histological lesions and high survival rates. Even though progress has been made in the knowledge of some of these mechanisms, new studies must be conducted which could target further prophylactic and therapeutic trials against T. cruzi infection. 展开更多
关键词 trypanosoma cruzi CHAGAS disease INNATE and adaptive IMMUNE response
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Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy 被引量:1
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作者 Ludmila Rodrigues Pinto Ferreira Amanda Farage Frade +4 位作者 Monique Andrade Baron Isabela Cunha Navarro Jorge Kalil Christophe Chevillard Edecio Cunha-Neto 《World Journal of Cardiology》 2014年第8期782-790,共9页
Chagas disease cardiomyopathy(CCC), the main consequence of Trypanosoma cruzi(T.cruzi) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC pat... Chagas disease cardiomyopathy(CCC), the main consequence of Trypanosoma cruzi(T.cruzi) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC patients is characterized by a Th1 T cell-rich myocarditis with increased production of interferon(IFN)-γ, produced by the CCC myocardial infiltrate and detected at high levels in the periphery. IFN-γ has a central role in the cardiomyocyte signaling during both acute and chronic phases of T.cruzi infection. In this review, we have chosen to focus in its pleiotropic mode of action during CCC, which may ultimately be the strongest driver towards pathological remodeling and heart failure. We describe here the antiparasitic protective and pathogenic dual role of IFN-γ in Chagas disease. 展开更多
关键词 Chagas disease trypanosoma cruzi INTERFERON-GAMMA Gene expression CARDIOMYOPATHY
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Antitrypanosomal Activity of a Semi-Purified Subfraction Rich in Labdane Sesquiterpenes, Obtained from Flowers of Anthemis Tinctoria, Against Trypanosoma Cruzi
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作者 Nilza de Lucas Rodrigues Bittencourt Tania Ueda-Nakamura +1 位作者 Benedito Prado Dias Filho Celso Vataru Nakamura 《Pharmacology & Pharmacy》 2011年第2期47-55,共9页
In Brazil and several other Latin American countries, Chagas' disease still constitutes a serious medical and social problem, and there is a need to develop new, more-potent drugs with fewer side effects to effect... In Brazil and several other Latin American countries, Chagas' disease still constitutes a serious medical and social problem, and there is a need to develop new, more-potent drugs with fewer side effects to effectively treat this disease. We investigated the antitrypanosomal effect of a crude extract, fractions, and a semi-purified subfraction rich in a mix- ture of isomeric labdane sesquiterpenes, obtained from flowers of Anthemis tinctoria, against Trypanosoma cruzi. In epimastigote forms, the aqueous crude extract, dichloromethane fraction, and semi-purified subfraction showed a dose-dependent inhibitory activity, with IC50 of 2.3 μg/ml, 1.8 μg/ml, and 0.2 μg/ml, respectively. In the interaction in- dex, the semi-purified subfraction showed a reduction in both the percentage of infected LLCMK2 cells and the mean number of amastigotes per infected cell. The cytotoxicity evaluation demonstrated that the cytotoxic concentrations of the semi-purified subfraction were higher for LLCMK2 cells than for the protozoans, with a selectivity index of 35.0. Epimastigote forms treated with the semi-purified subfraction showed ultrastructural and morphological alterations such as rounding of the cells and bleb formation in the flagellum and cytoplasmic membrane. These results show that the flowers from A. tinctoria may be a source of new drugs with antiprotozoal activity. However, additional in vitro and in vivo studies are needed to validate the use of A. tinctoria in the treatment of Chagas’ disease. 展开更多
关键词 Antiprotozoan Activity Medicinal Plants trypanosoma cruzi ULTRASTRUCTURE Alterations
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Synthesis and Trypanocidal Evaluation of Some Novel 2-(Substituted Benzylidene)-5, 7-Dibromo-6-Hydroxy-1-Benzofuran-3(2<i>H</i>)-Ones
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作者 K. L. Ameta Nitu S. Rathore +4 位作者 Biresh Kumar Edith S. Malaga M Manuela Verastegui P Robert H. Gilman B. L. Verma 《International Journal of Organic Chemistry》 2012年第3期295-301,共7页
Substituted 2-benzylidene-1-benzofuran-3-ones are commonly known as aurones. This class of bioactive heterocycles belongs to flavonoid family. The article intends to put forth the rational design and synthesis of a ne... Substituted 2-benzylidene-1-benzofuran-3-ones are commonly known as aurones. This class of bioactive heterocycles belongs to flavonoid family. The article intends to put forth the rational design and synthesis of a new series of aurones using 3’,5’-dibromo-2’,4’-dihydroxychalcones and copper bromide in presence of DMF-water mixture (8:2, v/v) for the first time. Preliminary bioassay shows that most of compounds have good trypanocidal activity against Trypanosoma cruzi at 10 μg/mL. Few compounds are equally potent to the standard drugs Benznidazole and Nifurtimox. The structures of the newly synthesized products 2a-n were established by elemental analysis, FTIR, 1H NMR, 13C NMR and mass spectroscopic studies. 展开更多
关键词 CHALCONES AURONES trypanosoma cruzi CHAGAS Disease Inhibition
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The association of Triatoma maculata(Ericsson 1848) with the gecko Thecadactylus rapicauda(Houttuyn 1782)(Reptilia:Squamata:Gekkonidae):a strategy of domiciliation of the Chagas disease peridomestic vector in Venezuela?
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作者 Reyes-Lugo M Reyes-Contreras M +7 位作者 Salvi I Gelves W Avilan A Llavaneras D Navarrete LF Cordero G Sanchez EE Rodriguez-Acosta A 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2011年第4期279-284,共6页
Objective:To investigate the bioecological relationship between Chagas disease peridomestic vectors and reptiles as source of feeding.Methods:In a three-story building,triatomines were captured by direct search and el... Objective:To investigate the bioecological relationship between Chagas disease peridomestic vectors and reptiles as source of feeding.Methods:In a three-story building,triatomines were captured by direct search and electric vacuum cleaner search in and outside the building.Then,age structure of the captured Triatoma maculata(T.maculata) were identified and recorded.Reptiles living in sympatric with the triatomines were also searched.Results:T.maculata were found living sympatric with geckos(Thecadactylus rapicauda) and they bit residents of the apartment building in study.A total of 1 448 individuals of T.maculata were captured within three days,of which 74.2%(1 074 eggs) were eggs,21.5%were nymphs at different stages,and 4.3%were adults.Conclusions:The association of T.maculata and T.rapicauda is an effective strategy of colonizing dwellings located in the vicinity of the habitat where both species are present;and therefore,could have implications of high importance in the intradomiciliary transmission of Chagas disease. 展开更多
关键词 CHAGAS disease GEKKONIDAE REDUVIIDAE Thecadactylus rapicauda TRIATOMA maculate trypanosoma cruzi VECTOR domiciliation
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Canova medication changes TNF-α and IL-10 serum levels in mice infected with Trypanosoma cruzi Y strain
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作者 áurea Regina Telles Pupulin Lívia Bracht +5 位作者 Márcia Machado de Oliveira Dalalio Francielli Maria de Souza Silva-Comar Bruno Ambrósio da Rocha Franciele Queiroz Ames Roberto Kenji Nakamura Cuman Ciomar Aparecida Bersani-Amado 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2016年第9期838-843,共6页
Objective:To identify whether Canova medication changes TNF-α and IL-10 serum levels in mice infected with Trypanosoma cruzi Y strain.Methods:Animals were divided into five groups:non-treated infected animals(I); ben... Objective:To identify whether Canova medication changes TNF-α and IL-10 serum levels in mice infected with Trypanosoma cruzi Y strain.Methods:Animals were divided into five groups:non-treated infected animals(I); benznidazole-treated infected animals(Bz; 100 mg/kg body weight,single daily dose by gavage); Canova medication(CM) treated infected animals(CM;0.2 mL/animal,single daily dose by gavage); benznidazole- and Canova medication–treated infected animals with the above-mentioned dose(Bz+CM);and non-infected animals(C).TNF-α and IL-10 levels were determined in serum aliquots after 4,7,10,13,and 29 days of infection.An ELISA technique was employed with R&D System Inc.antibody pairs.Results:A high increase in TNF-α and IL-10 levels occurred in the infected and CM-treated groups within the treatment employed on the 10 th day after infection,coupled with a IL-10 decrease on the 13 th day after infection when compared with the other experimental groups.Conclusions:CM may change the balance between plasma cytokine levels(TNF-α and IL-10) in mice infected with Y strain T.cruzi,with important consequences leading towards a more severe infection. 展开更多
关键词 trypanosoma cruzi Canova MEDICATION CYTOKINES
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Antibody delivery into viable epimastigotes of <i>Trypanosoma cruzi</i>as a tool to study the parasite biology
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作者 Karla Y. Acosta-Viana Huchin-Cetz Julio +2 位作者 Jimenez-Coello Matilde Guzman-Marin Eugenia Jose L. Rosales-Encina 《Advances in Bioscience and Biotechnology》 2013年第6期719-726,共8页
American trypanosomiasis is a zoonosis of worldwide medical importance and currently there is no effective treatment in chronic patients, hence the importance of the study of protein function of the parasite with the ... American trypanosomiasis is a zoonosis of worldwide medical importance and currently there is no effective treatment in chronic patients, hence the importance of the study of protein function of the parasite with the objective of finding new drug targets and to know better the biology of the agent causal (Trypano-soma cruzi). T. cruzi is an RNAi-negative parasite, therefore the silencing genes strategies by RNAi is not possible;for that reason, antibodies may be taken as a tool for studying the parasite proteins function by blocking these molecules with specific antibodies. The aim of this work was to establish a methodology for antibody delivery (antibody transfection) into viable parasites. We used anti-cyclin-A antibody (human origin) in western blot assay with epimastigote of T. cruzi proteins and this recognized a ~55 kDa polypeptide. Several methods for antibody transfection (electroporation, saponin permeabilization and a lipid-based formulation) were tested. The first two methods were unsuccessful. In electroporation was impossible to visualize the antibody inside parasites and with saponin permeabilization, antibodies were successfully introduced, but with loss of parasites viability. The lipid-based formulation method forms noncovalent complexes with antibodies. These complexes are internalized by cells and antibodies are released into the cytoplasm. With this method, a successful antibody delivery was achieved. Anti-cyclin antibodies were visualized in the cytoplasm from fixed transfected parasites (immunofluorescence assays). At 24 h post-transfection, parasites maintained their viability (90%) and were able to arrest the cell cycle in G0/G1-phase of cultured epimastigotes (cell population increased in G0/G1-phase from 50.5% to 66.2% and decreased in S-phase from 47.2% to 26%). It was also observed that anti-cyclin-A antibodies inhibit the parasite population doubling (p T. cruzi, with a simple and cheap technique, which will allows carrying out further studies of this protozoan. 展开更多
关键词 trypanosoma cruzi ANTIBODY Delivery ANTIBODY Transfection Cell Cycle Anti-Cyclin-A ANTIBODY
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Intra-Domiciliary Transmission of Chagas’ Disease in Rural Areas of Yucatan Mexico
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作者 Eugenia Guzman-Marin Karla Y. Acosta-Viana +2 位作者 Marylin Puerto-Solís Antonio Ortega-Pacheco Matilde Jimenez-Coello 《Open Journal of Epidemiology》 2016年第4期244-255,共12页
With the objective to describe the relationship between T. cruzi infection in humans and sinantropic reservoir and vectors in the rural conditions a study was performed in municipalities of the Yucatan state in Mexico... With the objective to describe the relationship between T. cruzi infection in humans and sinantropic reservoir and vectors in the rural conditions a study was performed in municipalities of the Yucatan state in Mexico. Blood samples from humans, dogs and opossum were taken from the households. Vectors were also collected and the infection and infestation indexes were calculated. Serum samples were evaluated by indirect hemagglutination (IH) and indirect immunofluorescence (IFI) to determine IgG antibodies against Trypanosoma cruzi. The polymerase chain reaction (PCR) was also performed in the samples taken from humans and reservoirs. Blood smears were performed in reservoirs. Sampled humans underwent to an electrocardiographic study to identify functional and conduction alterations of the heart. Household building characteristics were noted. A total of 367 blood samples were collected from people. The presence of IgG antibodies was 16.6% and 71.0% at PCR. Electrocardiographic studies revealed that 31% of patients seropositive to T. cruzi have a medical condition. 20.0% of dogs were seropositive and 68.5 positive to PCR. At the direct detection 13.6% resulted positive. In opossum 29.1% were seropositive and 72.9% positive to PCR. A total of 269 triatomineos were captured and 52.7% were infected with T. cruzi. The infection and infestation index were 52.4% and 60.8% respectively. The presence of adult vectors and their nymph’s were more frequently found in households made with wattle roofs (45.2 and 73.9 % respectively) than other kind of building materials. Electrocardiographic abnormalities found in positive persons were: Incomplete right bundle branch block (55%), tachycardia (35%), old myocardial infarction (5%) and incomplete block of the left bundle (5%). This work highlights the importance of comprehensive studies on the transmission of T. cruzi in the Yucatan where the link between human infection in synanthropic reservoirs and vectors is established. This information is important to design programs for t 展开更多
关键词 trypanosoma cruzi VECTORS SEROLOGY PCR Zoonosis.
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Specific primers design based on the superoxide dismutase b gene for Trypanosoma cruzi as a screening tool:Validation method using strains from Colombia classified according to their discrete typing unit
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作者 Francisco Olmo Javier Escobedo-Ortegón +4 位作者 Patricia Palma Manuel Sánchez-Moreno Ana Mejía-Jaramillo Omar Triana Clotilde Marín 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2014年第11期854-859,共6页
Objective:To classify 21 new isolates of Trypanosoma cruai(T.cruzi) according to the Discrete Typing Unit(DTU) which they belong to,as well as tune up a new pair of primers designed to detect the parasite in biologica... Objective:To classify 21 new isolates of Trypanosoma cruai(T.cruzi) according to the Discrete Typing Unit(DTU) which they belong to,as well as tune up a new pair of primers designed to detect the parasite in biological samples.Methods:Strains were isolated,DNA extracted,and classified by using three Polymerase Chain Reactions(PCR).Subsequently this DNA was used along with other isolates of various biological samples,for a new PCR using primers designed.Finally,the amplified fragments were sequenced.Results:It was observed the predominance of DTU i in Colombia,as well as the specificity of our primers for detection of T.cruzi,while no band was obtained when other species were used.Conclusions:This work reveals the genetic variability of 21 new isolates of T.cruzi in Colombia.Our primers confirmed their specificity for detecting the presence of T.cruzi. 展开更多
关键词 trypanosoma cruzi Polymerase chain reaction Colombia Superoxide dismutase GENE b-based primers DISCRETE TYPING UNIT
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美洲锥虫病——美洲新型艾滋病 被引量:2
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作者 朱来华 王宁宁 +8 位作者 王树峰 邓明俊 肖西志 孙涛 魏乃林 于红光 赵玉然 郑小龙 王群 《动物医学进展》 CSCD 北大核心 2013年第5期115-121,共7页
美洲锥虫病,又称查加斯病,是由克氏锥虫引起的潜在致命的寄生虫性人兽共患病。除人外,在美洲200多种哺乳动物感染了克氏锥虫。人和动物感染的主要传播媒介为吸血昆虫——锥蝽,偶尔通过非吸血昆虫媒介机制传播,如输血、污染食品、母婴感... 美洲锥虫病,又称查加斯病,是由克氏锥虫引起的潜在致命的寄生虫性人兽共患病。除人外,在美洲200多种哺乳动物感染了克氏锥虫。人和动物感染的主要传播媒介为吸血昆虫——锥蝽,偶尔通过非吸血昆虫媒介机制传播,如输血、污染食品、母婴感染。该病的临床症状因感染阶段不同而异,早期急性期无症状或症状轻微,隐匿期亦无症状,慢性期的典型症状为渐进性慢性心脏和消化系统损害,持续终生,部分病例死亡。因克氏锥虫与人免疫缺陷病毒(HIV)的早期传播模式、漫长的潜伏期和难以治愈等方面极其相似,有专家将查加斯病称为"美洲的新艾滋病"。该病曾局限于美洲地区,但现已随人口迁移传播到欧洲等大陆,成为全球性疫病。在急性期,使用苄硝唑和硝呋替莫抗寄生虫药物治疗很有效;在慢性期,也可延迟或防止症状恶化,但仍有部分慢性病例最终发展成致命的心脏和消化道衰竭。查加斯病可通过病原鉴定、血清学和分子学技术进行诊断。目前尚无查加斯病疫苗,媒介昆虫控制是最有效的预防手段。论文详细介绍了美洲锥虫病的病原学、生活史、流行病学、临床症状、病理变化、诊断、治疗以及防控措施,以供参考。 展开更多
关键词 美洲锥虫病 查加斯病 克氏锥虫 锥蝽
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两种锥虫双重实时荧光PCR检测方法的建立
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作者 王渊 刘永杰 +4 位作者 金子懿 王文博 付强 王爽 高毅 《中国口岸科学技术》 2022年第2期4-8,共5页
通过比较美洲锥虫和非洲锥虫基因组的保守性与特异性,设计2套锥虫特异性引物和探针用于核酸检测,美洲锥虫和非洲锥虫分别使用HEX和FAM荧光基团标记探针,建立美洲锥虫和非洲锥虫的双重实时荧光PCR检测方法,并对建立的方法进行灵敏度、特... 通过比较美洲锥虫和非洲锥虫基因组的保守性与特异性,设计2套锥虫特异性引物和探针用于核酸检测,美洲锥虫和非洲锥虫分别使用HEX和FAM荧光基团标记探针,建立美洲锥虫和非洲锥虫的双重实时荧光PCR检测方法,并对建立的方法进行灵敏度、特异性和重复性分析。结果显示,新建立的双重实时荧光PCR检测方法只对2种锥虫阳性对照模板有特异性扩增,与健康人血液、健康人尿液、钩端螺旋体、丝虫阳性对照样本均无交叉反应。2套引物和探针的检测灵敏度均可达到最低10^(-4)拷贝/mL。美洲锥虫和非洲锥虫阳性对照模板的2种稀释度重复检测10次均有较好的重复性。结果表明,建立的2种锥虫双重实时荧光PCR检测方法灵敏度高,特异性强,重复性好,可用于对我国口岸输入性锥虫病例的早期检测和分型鉴别。 展开更多
关键词 美洲锥虫 非洲锥虫 双重实时荧光PCR
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细菌脂多糖促进克氏锥虫抗原诱导的自身免疫性心肌炎
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作者 林爱芬 颜卫华 +1 位作者 余素飞 Wang Kegiang 《中国人兽共患病杂志》 CSCD 北大核心 2005年第12期1094-1096,1118,共4页
目的观察细菌脂多糖(LPS)对克氏锥虫抗原诱导自身免疫性心肌炎的影响。方法克氏锥虫抗原辅以完全弗氏佐剂免疫A/J小鼠,LPS经腹腔接种方式给药,其后加强免疫2次,28 d后,测定心肌肌球蛋白特异的迟发型超敏反应(DTH)及自身抗体,并取鼠心脏... 目的观察细菌脂多糖(LPS)对克氏锥虫抗原诱导自身免疫性心肌炎的影响。方法克氏锥虫抗原辅以完全弗氏佐剂免疫A/J小鼠,LPS经腹腔接种方式给药,其后加强免疫2次,28 d后,测定心肌肌球蛋白特异的迟发型超敏反应(DTH)及自身抗体,并取鼠心脏观察心肌炎症情况。结果LPS提高锥虫抗原诱导的心肌肌球蛋白特异性DTH及自身抗体,并且25μg LPS与锥虫抗原免疫的小鼠可见明显的心肌炎。结论LPS能够促进心肌肌球蛋白特异的自身免疫反应及锥虫抗原诱导的自身免疫性心肌炎。 展开更多
关键词 细菌脂多糖(LPS) 克氏锥虫 肌球蛋白 自身免疫性心肌炎
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Comparison of biological fitness in crosses between subspecies of Meccus phyllosomus (Hemiptera: Reduviidae: Triatominae) in southern Mexico 被引量:1
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作者 Jose Alejandro Martinez-Ibarra Benjamin Nogueda-Torres +3 位作者 Luis Fernando Salazar-Montano Juan Carlos Garcia-Lino Demver Arroyo-Reyes Juan Angel Hernandez-Navarro 《Insect Science》 SCIE CAS CSCD 2017年第1期114-121,共8页
Understanding the biological parameters of some triatomine subspecies of Meccus phyllosomus (Burmeister) is a crucial first step in estimating the epidemiologie importance of this group. Biological parameters relate... Understanding the biological parameters of some triatomine subspecies of Meccus phyllosomus (Burmeister) is a crucial first step in estimating the epidemiologie importance of this group. Biological parameters related to hatching, lifetime, number of blood meals to molt, percentage of females at the end of the cycle, number of laid eggs, and mortality for each instar of 3 M. phyllosomus subspecies [M. p. mazzottii (Usinger), M. p. pallidipennis (Stal), and M. p. phyllosomus] and their laboratory hybrids were evaluated and compared. No significant differences (P 〉 0.05) were found among the experimental hybrids (MaPa, MaPhy, PaPhy) and reciprocal cohorts. In 5 (hatching, number of blood meals to molt, accumulative mortality, percentage of females, and mean number of laid eggs) of the 6 studied parameters (with the exception of development time), the hybrid cohorts had better fitness results than the parental cohorts involved in each set of crosses. The increase in hybrid fitness found in our study could lead to an increase in the epidemiologic risks caused by transmission of Trypanosoma cruzi to humans. 展开更多
关键词 biological parameters Chagas disease Meccus subspecies Mexico tri- atomines trypanosoma cruzi transmission
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Challenges in the chemotherapy of Chagas disease: Looking for possibilities related to the differences and similarities between the parasite and host 被引量:1
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作者 Vitor Sueth-Santiago Debora Decote-Ricardo +2 位作者 Alexandre Morrot Celio Geraldo Freire-de-Lima Marco Edilson Freire Lima 《World Journal of Biological Chemistry》 CAS 2017年第1期57-80,共24页
Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countr... Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countries. This short review highlights the enormous need for new studies aimed at the development of novel and more specific drugs to treat chagasic patients. The primary tool for facing this challenge is deep knowledge about the similarities and differences between the parasite and its human host. 展开更多
关键词 trypanosoma cruzi Trans-sialidase Trypanothione reductase CYP51 cruzipain TUBULIN
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萘酰肼类化合物的合成设计及其抑制克鲁斯氏锥体虫半胱氨酸蛋白酶的活性
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作者 程卯生 张莉 +2 位作者 闫冬 陈娥功 沈建民 《中国药物化学杂志》 CAS CSCD 2002年第4期187-193,共7页
目的卡格氏病 (Chagas′disease)是由克鲁斯氏锥体虫引起的一种寄生虫病 ,克鲁斯氏锥体虫半胱氨酸蛋白酶 (cruzain)是锥体虫生活周期中起重要作用的一种酶 ,研究该酶的抑制剂可望发展出一类治疗卡格氏病的新药。方法采用DOCK程序对前期... 目的卡格氏病 (Chagas′disease)是由克鲁斯氏锥体虫引起的一种寄生虫病 ,克鲁斯氏锥体虫半胱氨酸蛋白酶 (cruzain)是锥体虫生活周期中起重要作用的一种酶 ,研究该酶的抑制剂可望发展出一类治疗卡格氏病的新药。方法采用DOCK程序对前期研究中的抑酶活性最强的萘酰肼化合物z1与cruzain拟合的情况进行了研究 ,辅助指导药物分子设计和化学结构修饰 ,设计了 7个目标化合物z2~z8,并采用酶法体外筛选测定其抗克鲁斯氏锥体虫活性。结果以 2 ,3 二羟基萘为起始原料 ,经甲醚化保护、硝化、还原、氮甲基化、甲酰化、脱保护基和缩合等共 7步反应 ,制得目标化合物N′ (2 ,3 二羟基 4 二甲氨基 1 萘亚甲基 ) 3 羟基 2 萘甲酰肼 (z7) ,其抑制cruzain的IC50 值约为 0 2 0 μmol L ,其活性强度是化合物z1的两倍多。结论目标化合物经1 H NMR和MS确定了其化学结构。目标化合物z7的抑制酶的活性大大增强 。 展开更多
关键词 萘酰肼类化合物 克鲁斯氏锥体虫半胱氨酸蛋白酶 抑制
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RIL—2对急性克氏锥虫感染小鼠的抗SRBC直接溶血空斑反应及抗虫保护性免疫影响的初步研究 被引量:1
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作者 薛燕萍 《寄生虫与医学昆虫学报》 CAS 1994年第4期1-6,共6页
为研究IL—2在克氏锥虫感染过程中出现的免疫抑制机制中的作用,8只克氏锥虫感染的C3H/HeJn小鼠每日皮下注射两次,每日总量5000μ重组人rIL-2;对照组相同数量小鼠皮下注射等量的无钙、镁离子的PBS。实验结果... 为研究IL—2在克氏锥虫感染过程中出现的免疫抑制机制中的作用,8只克氏锥虫感染的C3H/HeJn小鼠每日皮下注射两次,每日总量5000μ重组人rIL-2;对照组相同数量小鼠皮下注射等量的无钙、镁离子的PBS。实验结果表明rIL-2注射组小鼠脾细胞对羊红细胞的反应能力由PBS注射鼠的15。2%提高到93。5%(P<0.05)。相当接近于正常的未感染小鼠的空斑形成细胞数。rIL-2注射组小鼠仅表现轻度降低的寄生虫血症,其动态变化在两组间未显示出差异。除PBS组的1只小鼠在感染后第36d死亡外,rIL-2以及PBS注射组的其它动物都在克氏锥虫急性感染期存活。尽管rIL-2注射并未明显地提高克氏锥虫急性感染期C3H/HeJn小鼠的抗虫保护性免疫,本实验提示IL-2不足是克氏锥虫急性感染期C3H/HeJn小鼠非特异性免疫抑制的原因之一。 展开更多
关键词 锥虫 克氏锥虫 感染 重组 白细胞介素2
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N,N′-双取代脲类克鲁斯氏锥体虫半胱氨酸蛋白酶小分子抑制剂的合成及其活性研究
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作者 郭春 Xiaohui Du +1 位作者 James H.McKERROW Fred E.Cohen 《中国药科大学学报》 CAS CSCD 北大核心 2003年第6期491-495,共5页
目的 :寻找克鲁斯氏锥体虫体半胱氨酸蛋白酶 (Cruzain)的小分子抑制剂。方法 :根据对Cruzain分子结构的计算机模拟设计结果 ,选用N ,N′ 双取代脲为先导结构 ,设计并合成了 2 1个未见文献报道的双取代脲衍生物 ,确证了它们的化学结构 ,... 目的 :寻找克鲁斯氏锥体虫体半胱氨酸蛋白酶 (Cruzain)的小分子抑制剂。方法 :根据对Cruzain分子结构的计算机模拟设计结果 ,选用N ,N′ 双取代脲为先导结构 ,设计并合成了 2 1个未见文献报道的双取代脲衍生物 ,确证了它们的化学结构 ,测定了化合物的体外抑制Cruzain的IC50 值。结果 :生物活性测定结果显示所合成的化合物均有不同程度的抑制Cruzain的活性 ,其中化合物Ⅳ8、Ⅳ9和Ⅳ1 7的活性与对照药tf 展开更多
关键词 克鲁斯氏锥体虫体半胱氨酸蛋白酶 抑制剂 N N'-双取代脲 合成 活性
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克氏锥虫唾液酸转移酶催化机理的理论研究
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作者 冯燕 管航敏 《计算机与应用化学》 CAS CSCD 北大核心 2012年第2期165-168,共4页
克氏锥虫唾液酸转移酶(TcTs)是恰加斯病的致病原,它具有由6个β片构成的桶状催化结构域。该催化结构域集中在酶N端的边缘。本文利用量子力学/分子力学(QM/MM)联用的模型研究了克氏锥虫唾液酸转移酶的催化机理。初始酶和底物复合物... 克氏锥虫唾液酸转移酶(TcTs)是恰加斯病的致病原,它具有由6个β片构成的桶状催化结构域。该催化结构域集中在酶N端的边缘。本文利用量子力学/分子力学(QM/MM)联用的模型研究了克氏锥虫唾液酸转移酶的催化机理。初始酶和底物复合物模型由蛋白质晶体数据库得到(PDB ID:lSOI)。其中QM部分在半经验模型中由AM1描述,在从头算模型中由B3LYP/6-3lG~*描述。MM部分只取酶的N端结构域,并始终由AMBER力场来描述。QM部分与MM部分成键相互作用边界用pseudo-bond方法处理,将3个重要的氨基酸残基(Glu230,Asp59,Tyr342)的C_β-C_β键作为OM/MM模型中的pseudo-bond。由Nudged Elastic Band(NEB)路径优化方法得到的TcTs半经验的最低能量反应路径中,关键原子间距离沿最低能量路径的变化表明:反应开始后Glu230开始靠近Tyr342,当它们之间的氢键距离由2.9 A缩短为2.4 A时,Tyr342将质子转移给Glu230,增强了Tyr342酚氧负离子的碱性,更有利于Tyr342亲核进攻糖苷键。同时,Asp59作为酸,提供质子给糖苷键断裂后的离去基团。过程中,伴随着唾液酸的单糖糖环从扭曲的船式构象向松弛的椅式构象的转变,从而更有利于稳定生成的共价唾液酸-酶中间产物。对得到的半经验的最低能量反应路径再做B3LYP/6-31G~*/MM模型下的优化,得到反应的能垒约为13.53 kcal/mol,说明该反应路径是合理的。研究结果与实验上通过突变的TcTs_(D59A)推测的乒乓双置换酸碱催化的机理一致,是对实验结论的有力支持,为TcTs抑制剂的设计和结构修饰提供了理论参考,有助于预防和抗恰加斯病的新药物研发。 展开更多
关键词 量子力学/分子力学模型 克氏锥虫唾液酸转移酶 催化机理
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