Disease relevance of Chagas Disease

• Although several good antiparasitic agents are available, new drugs are needed for the treatment of diseases such as chloroquine-resistant malaria, Chagas' disease, leishmaniasis and filariasis [1].
• BACKGROUND & AIMS: Autoantibodies against M(2)-muscarinic acetylcholine receptors (M(2) mAChR) have been reported in patients with chronic Chagas' disease who have cardiac dysautonomia [2].
• Consequently, TR is an attractive target molecule for a structure-based drug development against Chagas' disease, African sleeping sickness, and other diseases caused by trypanosomes and leishmanias [3].
• Trypanosoma cruzi, the agent of Chagas' disease, an ailment characterized by a progressive chronic fibrotic myocarditis and degeneration of tissues that are innervated by the autonomic nervous system, is a voracious sialic acid eater from glycoconjugates of the surrounding medium [4].
• Immunologically, La gp42 is strongly recognized by sera from patients with different forms of leishmaniasis as well as by patients with Chagas' disease [5].

Psychiatry related information on Chagas Disease

• Antibodies (Abs) were purified from pooled sera of patients with either indeterminate (IND or I) or cardiac (CARD or C) Chagas' disease, on either epimastigote (EPI or E) or amastigote-enriched (AMAST or A) antigen (Ag) columns and their idiotypic (Id) expression examined [6].

High impact information on Chagas Disease

• Of the 25 patients, 18 had been treated for coronary artery disease or idiopathic dilated cardiomyopathy for up to 108 months before the diagnosis of Chagas' disease was considered [7].
• Transmission of Chagas' disease by transfusion of blood containing Trypanosoma cruzi has often been reported, and gentian violet, a triarylmethane dye, is widely used by blood banks in attempts to eliminate such transmission [8].
• Epimastigotes, the invertebrate host stage of Trypanosoma cruzi, the protozoan parasite causing Chagas' disease in man, were fused with vertebrate cells by using polyethylene glycol [9].
• Analysis of trypomastigote transfectants expressing various cysteine proteinase isoforms showed that invasion competence is linked to the kinin releasing activity of cruzipain, herein proposed as a factor of virulence in Chagas' disease [10].
• The virulence-promoting activity of soluble trans-sialidase in the mouse model may be physiologically relevant because it was achieved with tiny doses, approximately 1-2 microgram/kg, raising the possibility that neutralization of the enzyme with specific probes could impair the development of Chagas' disease [11].

Chemical compound and disease context of Chagas Disease

• Should benznidazole be used in chronic Chagas' disease [12]?
• BACKGROUND: Benznidazole, a nitroimidazole derivative, has been recommended for the treatment of acute and congenital Trypanosoma cruzi infection (Chagas' disease) [13].
• Dinitrochlorobenzene and Chagas' disease [14].
• In the patients with Chagas' disease the mean concentrations of rectal vasoactive intestinal polypeptide, enteroglucagon, substance P, and somatostatin were all less than half of those in controls and in patients with chronic autonomic failure [15].
• "Subversive" substrates for the enzyme trypanothione disulfide reductase: alternative approach to chemotherapy of Chagas disease [16].

Biological context of Chagas Disease

• Autoimmunity in chagas disease cardiomyopathy: Fulfilling the criteria at last [17]?
• Trypanosoma cruzi antigenic specificities involved in human T-cell and antibody responses were compared in chronic chagasic patients affected with cardiomyopathy (C) or with the indeterminate form (I), the asymptomatic form of chronic Chagas' disease [18].
• Trypanosoma cruzi, the agent of Chagas disease, expresses on its surface a trans-sialidase that catalyzes preferentially the transference of alpha-2,3-linked sialic acid to acceptors containing terminal beta-galactosyl residues, instead of the typical hydrolysis reaction, found in most sialidases [19].
• Nifurtimox (NF) and benznidazole (BZ), drugs used in the treatment of Chagas' disease, did not inhibit protein biosynthesis in in vitro homologous cell-free systems isolated from Trypanosoma cruzi and Crithidia fasciculata; nevertheless, their addition to growing cultures caused polyribosomal depolymerization [20].
• The availability of the hgprt clone and large amounts of pure HGPRT protein provide a foundation for a structure-based drug design strategy for the treatment of Chagas disease [21].

Anatomical context of Chagas Disease

• Dominant T- and B-cell epitopes in an autoantigen linked to Chagas' disease [22].
• IL-12-independent IFN-gamma production by T cells in experimental Chagas' disease is mediated by IL-18 [23].
• Suppression of IL-2 production during experimental Chagas' disease accounts at least in part for the overall depressed state of the immune system in infected mice [24].
• OBJECTIVES: To determine whether dobutamine stimulation in patients with Chagas' disease may uncover abnormal contractile responses as seen in ischemic myocardium [25].
• Although ex vivo expression of CD11b was similar among the groups, in vitro infection led to decreased expression of this molecule by monocytes from Chagas' disease patients but not from noninfected individuals [26].

Gene context of Chagas Disease

• Chemokine receptor expression on the surface of peripheral blood mononuclear cells in Chagas disease [27].
• Chronic Chagas' disease cardiomyopathy patients display an increased IFN-gamma response to Trypanosoma cruzi infection [28].
• These results replicate previous analyses and suggest that presence of epistasis between MHC with humoral systems, such as IL-10, could be underlying the susceptibility/resistance to Chagas' disease [29].
• Atrophy of mesenteric lymph nodes in experimental Chagas' disease: differential role of Fas/Fas-L and TNFRI/TNF pathways [30].
• Our present data further contribute to clarifying aspects of the role of A2MR/LRP in a model of acute Chagas' disease in different mouse strains [31].

Analytical, diagnostic and therapeutic context of Chagas Disease

• We have recently described the application of a purified glycoprotein of 25,000 Mr (GP25) of Trypanosoma cruzi in serodiagnosis of Chagas' disease [32].
• Felipe Kierzenbaum and Marcelo Sztein discuss recent advances in our understanding of the processes that lead to impaired human lymphocyte function and that might be involved in the immunosuppression seen in the acute phase of Chagas disease [33].
• Synthetic peptides comprising the 13 (R-13), 10 (R-10), and 7 (R-7) carboxyl-terminal residues of the JL5 protein were used to study, by enzyme-linked immunosorbent assay, the specificity of the Chagas' disease anti-JL5 and SLE anti-P antibodies [34].
• Gentian violet has been used in medicine for almost 100 years: as an antiseptic for external use, as an antihelminthic agent by oral administration, and more recently, as a blood additive to prevent transmission of Chagas' disease [35].
• No cases have been reported involving other organ transplants up to 2002, when the Centers for Disease Control and Prevention reported 3 cases of Chagas' disease transmission to 3 recipients (liver, kidney, and pancreas-kidney) from a single chagas infected donor [36].

References