Chagas Disease - Basic Investigations and Challenges最新文献

New Approaches for Chagas’ Disease Chemotherapy 恰加斯病化疗的新方法

Chagas Disease - Basic Investigations and Challenges Pub Date : 2018-09-12 DOI: 10.5772/INTECHOPEN.77235

G. G. Liñares

{"title":"New Approaches for Chagas’ Disease Chemotherapy","authors":"G. G. Liñares","doi":"10.5772/INTECHOPEN.77235","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77235","url":null,"abstract":"The latest advances concerning drug design and chemotherapy development to combat the Chagas’ disease are discussed. This chapter is based on the metabolic differences between the pathogenic parasite and mammal hosts that led to the progress in the search for novel metabolic pathways in parasites that may be essential for parasite’s survival but with no counterpart in the host. There is a considerable amount of work in the search of more promising molecular targets for drug design. However, the chemotherapy for this disease remains unsolved. It is based on old and fairly not specific drugs associated with long-term treatments, severe side effects, drug resistance, and different strains’ suscep -tibility. Herein, a thorough analysis of selected molecular targets is described in terms of their potential usefulness for drug design. Therefore, rational approaches to the chemotherapeutic control of American trypanosomiasis describing some useful metabolic pathways are covered. Enzymes involved in ergosterol biosynthesis (squalene synthase, HMG-CoA reductase, farnesyl diphosphate synthase (FPPS), sterol 24-methyltransferase, and sterol 14α-demethylase), trypanothione system (glutathionyl-spermidine synthe -tase, trypanothione synthetase, and trypanothione reductase), cysteine proteases, trans- sialidase, and so on are discussed. The design of specific inhibitors of these metabolic activities as possible means of controlling the parasites without damaging the hosts is presented.","PeriodicalId":294754,"journal":{"name":"Chagas Disease - Basic Investigations and Challenges","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125941327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Biochemical, Cellular, and Immunologic Aspects during Early Interaction between Trypanosoma cruzi and Host Cell 克氏锥虫与宿主细胞早期相互作用的生化、细胞和免疫方面

Chagas Disease - Basic Investigations and Challenges Pub Date : 2018-09-12 DOI: 10.5772/INTECHOPEN.77236

R. Solis-Oviedo, V. Monteón, R. López, Á. Pech-Canul

引用次数: 1

Antiparasitic Mechanisms of the Human Placenta 人胎盘的抗寄生虫机制

Chagas Disease - Basic Investigations and Challenges Pub Date : 2018-09-12 DOI: 10.5772/INTECHOPEN.73569

Castillo Christian, A. Liempi, Lisvaneth Medina, Ileana Carrillo, U. Kemmerling

引用次数: 1

Slowed Development of Natural Products for Chagas Disease, how to Move Forward? 治疗恰加斯病的天然产物发展缓慢，如何向前推进?

Chagas Disease - Basic Investigations and Challenges Pub Date : 2018-09-12 DOI: 10.5772/INTECHOPEN.77234

J. Varela, H. Cerecetto, Mercedes González

{"title":"Slowed Development of Natural Products for Chagas Disease, how to Move Forward?","authors":"J. Varela, H. Cerecetto, Mercedes González","doi":"10.5772/INTECHOPEN.77234","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77234","url":null,"abstract":"Chagas disease, caused by Trypanosoma cruzi , is considered an endemic disease that affects millions of people causing generating health, economic and social problems. This study provides a review on research and development of new therapies for Chagas based in natural products of plant origin. We observed that there are more than 400 plant spe - cies that have been evaluated against different models of Chagas disease, and in some cases, there are interesting results. Challenge that hinders research work is the puri - fication of the active compound and standardization of the chemical profile of whole extracts. The principal common factor that delays clinical testing is the lack of investment for the development of these products at the clinical phase. In the search of a natural, low cost and available drug for Chagas disease, we propose the use of new methodologies to overcome the existing challenges. The use of plant metabolomic technique is proposed as an option with high potential for the identification of biomarkers that could allow the standardization of chemical profiles. Furthermore, we describe the importance of apply ing good agricultural and manufacturing practices for reaching a successful development of quality phytotherapeutic products.","PeriodicalId":294754,"journal":{"name":"Chagas Disease - Basic Investigations and Challenges","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125367696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Transmitter Insect of Chagas Disease in Northwest Mexico: A Comparative Study of the Cuticular Hydrocarbons Profile of Three Populations of Triatoma rubida: Peridomestic, Domestic and Sylvatic 墨西哥西北部恰加斯病的传播昆虫:三个种群:家、家和林中斑蝽表皮碳氢化合物分布的比较研究

Chagas Disease - Basic Investigations and Challenges Pub Date : 2018-09-12 DOI: 10.5772/INTECHOPEN.77169

J. Ortega-García, G. Hernandez

{"title":"Transmitter Insect of Chagas Disease in Northwest Mexico: A Comparative Study of the Cuticular Hydrocarbons Profile of Three Populations of Triatoma rubida: Peridomestic, Domestic and Sylvatic","authors":"J. Ortega-García, G. Hernandez","doi":"10.5772/INTECHOPEN.77169","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77169","url":null,"abstract":"In México, biogeography data are available for species of triatomas called Trypanosoma cruzi transmitters; for example, the phyllosoma complex is distributed in several states of the south-central southeast of the country. In contrast, Northwestern Mexico species such as Triatoma rubida are considered sylvatic and in the process of domestication. The lack of research of these northern species of the country has generated an ignorance that contrasts with a growing number of alleged new cases of Chagas disease registered in health institutions in states such as Sonora. From the six species of triatomas that are potential transmitters of the trypanosoma in the state of Sonora, Triatoma rubida is the only one that has recent studies of distribution and transmission capacity. It is important then to know the degree of domesticity of the native species with the capacity of transmission of Trypanosoma cruzi and to define areas of risk. The process of adaptation of the sylvatic triatomines to the peridomestic and the domestic habitat has been understood in terms of environmental and biological variables. In this research, the profile of cuticular hydrocarbons of a peridomestic, domestic and sylvatic population of Triatoma rubida was analyzed and compared. distinctions can be made between populations. The profile of cuticular hydrocarbons, identified in this study, can be used as a reliable chemotaxonomic tool to identify the populations of T. rubida , considering the expression of hydrocarbons as the chemical phenotype of the vector that responds to environmental and biological factors of the insect.","PeriodicalId":294754,"journal":{"name":"Chagas Disease - Basic Investigations and Challenges","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115313223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Silent Information Regulator 2 from Trypanosoma cruzi Is a Potential Target to Infection Control 克氏锥虫沉默信息调控因子2是控制感染的潜在靶点

Chagas Disease - Basic Investigations and Challenges Pub Date : 2018-09-12 DOI: 10.5772/INTECHOPEN.77030

Luís Gaspar, Terry K. Smith, N. Moretti, S. Schenkman, A. Cordeiro-da-Silva

{"title":"Silent Information Regulator 2 from Trypanosoma cruzi Is a Potential Target to Infection Control","authors":"Luís Gaspar, Terry K. Smith, N. Moretti, S. Schenkman, A. Cordeiro-da-Silva","doi":"10.5772/INTECHOPEN.77030","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77030","url":null,"abstract":"Human trypanosomiasis is a neglected tropical disease caused by protozoan parasites of the genus Trypanosoma . Trypanosoma brucei is responsible for sleeping sickness, also called African trypanosomiasis, while Trypanosoma cruzi causes Chagas disease, or American trypanosomiasis. Together, these diseases are responsible for significant mortality, mor-bidity and lost productivity in the endemic regions. There are no vaccines and treatments rely on drugs with limited efficacy, high cost, serious side effects and long administration periods. Since these diseases affect mostly the poor, there is no economic interest in the development of new drugs by pharmaceutical companies, and hopes for new treatments rely on public initiatives, public-private partnerships or philanthropic programs. The first step in the discovery of new drugs involves the identification of active molecules as starting points for further development, by either employing whole cells or by specific molecular target screenings. Research efforts undertaken by the authors ’ groups have focused on exploiting both strategies in the search for new molecules for trypanosomiasis drug discovery. In this chapter, we focus on Chagas disease and the recently uncovered potential of using sirtuins as targets for infection control. proliferation might be instrumental to mediate tissue integrity during aging.","PeriodicalId":294754,"journal":{"name":"Chagas Disease - Basic Investigations and Challenges","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124951218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Mouse Model as a Tool for Histological, Immunological and Parasitological Studies of Trypanosoma cruzi Infection 克氏锥虫感染小鼠模型的组织学、免疫学和寄生虫学研究

Chagas Disease - Basic Investigations and Challenges Pub Date : 2018-09-12 DOI: 10.5772/INTECHOPEN.77168

M. Villagrán-Herrera, J. Martínez-Ibarra, M. Sánchez-Moreno, H. Hernández-Montiel, R. Mercado-Curiel, N. Camacho-Calderón, J. D. Diego-Cabrera

{"title":"The Mouse Model as a Tool for Histological, Immunological and Parasitological Studies of Trypanosoma cruzi Infection","authors":"M. Villagrán-Herrera, J. Martínez-Ibarra, M. Sánchez-Moreno, H. Hernández-Montiel, R. Mercado-Curiel, N. Camacho-Calderón, J. D. Diego-Cabrera","doi":"10.5772/INTECHOPEN.77168","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77168","url":null,"abstract":"The global expansion of Chagas disease is due to the constant migration of individu- als from endemic countries with incidence of vector and nonvector transmission of Trypanosoma cruzi . The disease is present in its various stages: chronological character-istic signs and symptoms of the infection and its mechanism of immune system and cell and tissue damage. The first stage, which lasts 90 days approximately, is diagnosed by direct methods (blood smears stained with Giemsa, fresh and xenodiagnosis). The indeterminate-chronic stage is asymptomatic, but the growth and intracellular binary multiplication of the trypomastigotes continue promoting cell lysis and allowing para- sites to infect other cells, with preferential tropism to organs producing mega syndromes such as cardiomyopathy, myocarditis, meningoencephalitis, megaesophagus and mega - colon. Inadvertently, this process is repeated for several years leading to Chagas disease. The mouse inoculation allows checking the parasitemia in vivo and the development of the disease in short time (signs, behavior and tropism), histopathological alterations and detection of antibodies in serum. These parameters may vary when using different strains of T. cruzi from different geographical areas; Triatoma species due to their genetic variability are influenced by the environment, nutrition, reservoirs and habitat. The murine model ECA CD-1 has the ability to replicate human findings of Chagas disease.","PeriodicalId":294754,"journal":{"name":"Chagas Disease - Basic Investigations and Challenges","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133739017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Introductory Chapter: Chagas Disease and Its Global Impacts 前言:恰加斯病及其全球影响

Chagas Disease - Basic Investigations and Challenges Pub Date : 2018-09-12 DOI: 10.5772/INTECHOPEN.77275

F. Masangkay, G. Milanez, H. Oz, V. Nissapatorn

{"title":"Introductory Chapter: Chagas Disease and Its Global Impacts","authors":"F. Masangkay, G. Milanez, H. Oz, V. Nissapatorn","doi":"10.5772/INTECHOPEN.77275","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77275","url":null,"abstract":"Soft tissue specimens from mummified remains of members of the Chinchorro culture of the Andean coast in South America have been found to be positive for Trypanosoma cruzi (T. cruzi) DNA [1]. The Chinchorros were fishermen inhabiting the pacific coastal region of northern Chile and southern Peru and T. cruzi the causative agent of American trypanosomiasis or Chagas disease is presently listed as one of the several neglected tropical diseases (NTDs) and as one of the five neglected parasitic infections (NPIs) of the world focused by the World Health Organization (WHO) and the Center for Disease Control (CDC) for public health intervention [2]. This finding spells out that the causative agent of American trypanosomiasis has been around for 9000 years already as the samples which tested positive are dated back to 7050 B.C. [1]. There are several historical accounts that have also mentioned about the prevalence of Chagas disease but some of these are just speculative assessments as signs and symptoms of patients were not consistent with the current pathophysiology of the disease. There were even speculations that Charles Darwin himself was infected with Chagas disease but popular opinions disagree as there were no actual clinical evidences to support that Charles Darwin was indeed suffering from megacolon or heart disease even later on in his life [3].","PeriodicalId":294754,"journal":{"name":"Chagas Disease - Basic Investigations and Challenges","volume":"569 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121199125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chagas Cardiomyopathy: Role of Sustained Host-Parasite Interaction in Systemic Inflammatory Burden 恰加斯心肌病:持续宿主-寄生虫相互作用在全身炎症负担中的作用

Chagas Disease - Basic Investigations and Challenges Pub Date : 2018-09-12 DOI: 10.5772/INTECHOPEN.77980

R. Kölliker-Frers, M. Otero-Losada, Gabriela Razzitte, M. Calvo, J. Carbajales, F. Capani

{"title":"Chagas Cardiomyopathy: Role of Sustained Host-Parasite Interaction in Systemic Inflammatory Burden","authors":"R. Kölliker-Frers, M. Otero-Losada, Gabriela Razzitte, M. Calvo, J. Carbajales, F. Capani","doi":"10.5772/INTECHOPEN.77980","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77980","url":null,"abstract":"The economic and social burden associated with Chagas disease morbidity and mortality is regrettably large in Latin America causing more deaths than does any other parasitic disease. Inflammatory dilated cardiomyopathy is, by far, the most important clinical consequence of Trypanosoma cruzi infection. The insidious persistence of this parasite determines chronic myocarditis progression. The clinical outcome is multifactorial and depends on the particular parasite strain and virulence factors, the infective load and route of infection, the parasite ability to by-pass the protective immune response, the intensity and type of immune response during the acute infective phase, and the host genetic background. From the immunological viewpoint, host control of T. cruzi has been shown to depend on both humoral and cell-mediated adaptive responses and from the innate immune system. In this review, we discuss the most relevant literature conveying information on the relevance of identifying a subset of systemic inflammatory molecules as potential markers of cardiovascular risk morbidity and mortality in patients with Chagas disease. Concurrently, a direct role for the parasite in the perpetuation of myocardial inflammation is substantiated. Ultimately, host-parasite interactions determine the course of the ongoing systemic inflammation and the perpetuation of myocardial inflammation in genetically predisposed patients.","PeriodicalId":294754,"journal":{"name":"Chagas Disease - Basic Investigations and Challenges","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125765826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Efficacy and Safety of Chagas Disease Drug Therapy and Treatment Perspectives 恰加斯病药物治疗的疗效和安全性及治疗前景

Chagas Disease - Basic Investigations and Challenges Pub Date : 2018-03-13 DOI: 10.5772/INTECHOPEN.74845

W. Kawaguchi, L. B. Cerqueira, M. Fachi, M. L. Campos, I. J. Reason, R. Pontarolo

引用次数: 6