Anin SituQuantitative Immunohistochemical Study of Cytokines and IL-2R+in Chronic Human Chagasic Myocarditis: Correlation with the Presence of MyocardialTrypanosoma cruziAntigens

Reis, Marlene Paulino dos; Higuchi, Maria de Lourdes; Benvenuti, Luiz Alberto; Aiello, Vera Demarchi; Gutierrez, Paulo Sampaio; Bellotti, Giovanni; Pileggi, F

doi:10.1006/clin.1997.4335

Cited by 162 publications

(130 citation statements)

References 39 publications

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“…Elimination is preferred because the existence of circulating parasites could promote the evolution of tissue lesions, which is characteristic of the chronic phase of the disease. Necropsies of chronic chagasic patients show that the persistence of parasitism is related to the presence of myocarditis (Chagas 1916, Reis et al 1997) and can possibly lead to death (Z Andrade, unpublished observations). However, considering the limitations of the tools currently available to monitor parasitological cure, a massive reduction in parasite load would be considered to be an important advance towards the identification of a new trypanocidal drug.…”

Section: For In Vitro Models For Chagas Disease Drug Discovery and Dementioning

confidence: 99%

In vitro and in vivo experimental models for drug screening and development for Chagas disease

Romanha

Castro

Soeiro

et al. 2010

Mem. Inst. Oswaldo Cruz

306

339

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Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Latin America. Although the occurrence of acute cases sharply has declined due to Southern Cone Initiative efforts to control vector transmission, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. This reflects, at least in part, the lack of consensus regarding appropriate in vitro and in vivo screening protocols as well as the lack of biomarkers for treating parasitaemia. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of the workshop entitled Experimental Models in Drug Screening and Development for Chagas Disease, held in Rio de Janeiro, Brazil, on the 25th and 26th of November 2008 by the Fiocruz Program for Research and Technological Development on Chagas Disease and Drugs for Neglected Diseases Initiative. During the meeting, the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease

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Section: For In Vitro Models For Chagas Disease Drug Discovery and Dementioning

confidence: 99%

In vitro and in vivo experimental models for drug screening and development for Chagas disease

Romanha

Castro

Soeiro

et al. 2010

Mem. Inst. Oswaldo Cruz

306

339

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“…However, a low level of inflammatory response constituted by macrophages and CD8 + T lymphocytes persist in the heart. Although often they are not associated with amastigote nests or trypomastigotes, T. cruzi antigens may be present (Higuchi 1995, Reis et al 1997). CD4 + T cells, though less prominent in the chronic stage, are suggested to be associated with myocyte death and increased animal mortality (Soares et al 2001) and appear to represent an autoreactive phenotype that contributes to tissue destruction (Soares and Santos 1999).…”

Section: Experimental Studiesmentioning

confidence: 99%

“…IP-10, MCP-1, MIG, and RANTES) that may be key regulators of the innate and adaptive immune responses responsible for the control of acute infection. CD4 + T cells assist in the control of T. cruzi through secretion of Th1 cytokines, amplifi cation of phagocytic activity of macrophages, and stimulation of B cell proliferation and antibody production (Aliberti et al 1996, Brener andGazzinelli 1997 (Higuchi et al 1997, Reis et al 1997. Again, CD8 + CTL are suggested to be likely the major effectors of pathogenesis, contributing to the development of fi brosis in response to cytopathology (Brener and Gazzinelli 1997).…”

mentioning

confidence: 99%

An overview of chagasic cardiomyopathy: pathogenic importance of oxidative stress

Zacks

Wen

Vyatkina

et al. 2005

An. Acad. Bras. Ciênc.

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There is growing evidence to suggest that chagasic myocardia are exposed to sustained oxidative stressinduced injuries that may contribute to disease progression. Pathogen invasion-and replication-mediated cellular injuries and immune-mediated cytotoxic reactions are the common source of reactive oxygen species (ROS) in infectious etiologies. However, our understanding of the source and role of oxidative stress in chagasic cardiomyopathy (CCM) remains incomplete. In this review, we discuss the evidence for increased oxidative stress in chagasic disease, with emphasis on mitochondrial abnormalities, electron transport chain dysfunction and its role in sustaining oxidative stress in myocardium. We discuss the literature reporting the consequences of sustained oxidative stress in CCM pathogenesis.Key words: chagasic cardiomyopathy, reactive oxygen species, inflammation, mitochondria, oxidant/antioxidant status, oxidative damage. PARASITE, VECTOR AND TRANSMISSIONTrypanosoma cruzi, a parasitic protozoan of the ancient branch of eukaryotes (Kingdom Eukaryota, Order Kinetoplastida), is the etiological agent of Chagas disease in humans (Miles 2003). Currently, the World Health Organization estimates that 11-18 million individuals are infected worldwide (WHO 2002). Transmission of T. cruzi occurs predominantly via insect vectors of the subfamily Triatoma, family Reduviidae, referred to as " kissing bugs". Residing in the peridomestic habitat of mud-thatch Correspondence to: Nisha Garg Ph.D. E-mail: nigarg@utmb.edu houses in rural areas (Mott et al. 1978), Triatoma infestans in South America, Rhodnius prolixus in Venezuela, Colombia and Central America (Schofi eld and Dias 1999), and Triatoma barberi in Mexico (Guzman 2001), are the most common species responsible for transmission. Improvements in housing conditions and vector control measures instituted by the Southern Cone Initiative in 1991 have contributed to a decline in transmission in endemic countries (Schofi eld and Dias 1999). However, concern remains that reinfestation of homes by secondary sylvatic vectors, e.g. Triatoma sordida, will compromise the long-term effi cacy of vector control measures in Brazil and other Southern American countries (Monteiro et al. 2001, WHO 2002. Blood transfusion and organ transplantation represent further routes of T. cruzi transmission. Although many countries in Latin America screen blood donations for T. cruzi, infection rates ranging from 0.1% to 24.4% are estimated to occur through transfusion (WHO 2002).In the U.S., vector-transmitted human infections have been reported in the southern States (Ochs et al. 1996, Herwaldt et al. 2000. Several studies have shown the presence of the insect vector as well as infection of domestic dogs and wild animals in the US (Meurs et al. 1998, Bradley et al. 2000, Beard et al. 2003, Yabsley and Noblet 2002. Further, due to signifi cant increases in immigration to the USA and Canada from endemic countries and perinatal transmission, it is estimated that ∼ 100, 000 people residing...

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“…The local cytokine production profile is consistent with a T1-type response, with interferongamma (γ)-induced chemokines (5)(6)(7)(8)(9)(10)(11)(12). Gene expression profiling of CCC myocardial tissues showed that 15% of the known genes selectively up-regulated in CCC are IFN-γ-inducible (12).…”

Section: Introductionmentioning

confidence: 60%

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy

Teixeira¹,

Iwai²,

Kuramoto³

et al. 2006

Braz J Med Biol Res

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Chronic Chagas' disease cardiomyopathy (CCC) is an often fatal outcome of Trypanosoma cruzi infection, with a poorer prognosis than other cardiomyopathies. CCC is refractory to heart failure treatments, and is the major indication of heart transplantation in Latin America. A diffuse myocarditis, plus intense myocardial hypertrophy, damage and fibrosis, in the presence of very few T. cruzi forms, are the histopathological hallmarks of CCC. To gain a better understanding of the pathophysiology of CCC, we analyzed the protein profile in the affected CCC myocardium. Homogenates from left ventricular myocardial samples of end-stage CCC hearts explanted during heart transplantation were subjected to two-dimensional electrophoresis with Coomassie blue staining; protein identification was performed by MALDI-ToF mass spectrometry and peptide mass fingerprinting. The identification of selected proteins was confirmed by immunoblotting. We demonstrated that 246 proteins matched in gels from two CCC patients. They corresponded to 112 distinct proteins. Along with structural/contractile and metabolism proteins, we also identified proteins involved in apoptosis (caspase 8, caspase 2), immune system (T cell receptor ß chain, granzyme A, HLA class I) and stress processes (heat shock proteins, superoxide dismutases, and other oxidative stress proteins). Proteins involved in cell signaling and transcriptional factors were also identified. The identification of caspases and oxidative stress proteins suggests the occurrence of active apoptosis and significant oxidative stress in CCC myocardium. These results generated an inventory of myocardial proteins in CCC that should contribute to the generation of hypothesis-driven experiments designed on the basis of the classes of proteins identified here.

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Anin SituQuantitative Immunohistochemical Study of Cytokines and IL-2R+in Chronic Human Chagasic Myocarditis: Correlation with the Presence of MyocardialTrypanosoma cruziAntigens

Cited by 162 publications

References 39 publications

In vitro and in vivo experimental models for drug screening and development for Chagas disease

In vitro and in vivo experimental models for drug screening and development for Chagas disease

An overview of chagasic cardiomyopathy: pathogenic importance of oxidative stress

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy

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