kDNA gene signatures of Trypanosoma cruzi in blood and oesophageal mucosa from chronic chagasic patients

Trypanosoma cruzi presents a high degree of intraspecific variability, with possible implications for the pathogenesis of Chagas disease. The aim of this study was to evaluate T cruzi kDNA minicircle gene signatures using the low-stringency single-specific-primer PCR technique in both peripheral blood and oesophageal. mucosa from chronic chagasic patients, with or without megaesophagus, atone or in combination with cardiopathy and megacolon. It was not possible to identify a uniform pattern of shared bands between blood and oesophageal mucosa samples from individuals with the same clinical. form or mixed forms, suggesting multiple T. cruzi infections with differential tissue tropism. Thus, the results indicate that there is an intense intraspecific variability in the hypervariable regions of T cruzi kDNA, which has so far made it impossible to correlate the genetic profile of this structure with the clinical manifestations of Chagas disease. (C) 2008 Royal. Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. AIL rights reserved.

Implications of genetic variability of Trypanosoma cruzi for the pathogenesis of Chagas disease

O Trypanosoma cruzi, agente etiológico da doença de Chagas, apresenta elevado grau de variabilidade genética intra-específica, com possíveis implicações na forma clínica da doença, como o desenvolvimento de cardiopatia, do megaesôfago e do megacólon de forma isolada ou em associação. Este tropismo tecidual envolvido na patogênese da doença não está totalmente esclarecido. Assim, nesta revisão são abordados alguns aspectos referentes à diversidade genética dos parasitas isolados, às formas clínicas da doença de Chagas, ao processo de infecção do parasita na célula hospedeira e resposta imune. Outros aspectos também são enfocados, como os fatores imunossupressivos liberados pelo parasita que atuam na regulação das respostas imunes, a inibição da apoptose da célula hospedeira, assim como da patogênese do megaesôfago chagásico que pode estar relacionada à interação hospedeiro- parasita e sua associação com risco aumentado para o desenvolvimento do carcinoma epidermóide do esôfago. Porém, apesar dos avanços no entendimento desta doença, ainda não é possível estabelecer o verdadeiro perfil da variabilidade genética do parasita com a forma clínica da doença de Chagas.

TOXIC DILATATION OF THE COLON IN CHAGAS-DISEASE

Toxic megacolon occurs in colitis of differing aetiology. This report describes 15 patients with chagasic megacolon with this complication. The clinical signs and symptoms in all patients were pain and progressive abdominal distension accompanied by fever, severe toxaemia and shock. Seven patients developed this clinical pattern after manual removal of faeces. The remaining patients had pain and abdominal distension followed by signs of severe toxaemia when first examined. Nine patients underwent total colectomy with ileostomy (one death), four partial colectomy (all died) and two received medical treatment (both died). At autopsy, three of the four patients undergoing partial colectomy had residual colitis and enteritis. The surgical procedure of choice for this complication of chagasic megacolon is total colectomy.

Chromosomal imbalances are uncommon in chagasic megaesophagus

Background: Chagas' disease is a human tropical parasitic illness and a subset of the chronic patients develop megaesophagus or megacolon. The esophagus dilation is known as chagasic megaesophagus (CM) and one of the severe late consequences of CM is the increased risk for esophageal carcinoma (ESCC). Based on the association between CM and ESCC, we investigated whether genes frequently showing unbalanced copy numbers in ESCC were altered in CM by fluorescence in situ (FISH) technology.Methods: A total of 50 formalin-fixed, paraffin-embedded esophageal mucosa specimens (40 from Chagas megaesophagus-CM, and 10 normal esophageal mucosa-NM) were analyzed. DNA FISH probes were tested for FHIT, TP63, PIK3CA, EGFR, FGFR1, MYC, CDKN2A, YES1 and NCOA3 genes, and centromeric sequences from chromosomes 3, 7 and 9.Results: No differences between superficial and basal layers of the epithelial mucosa were found, except for loss of copy number of EGFR in the esophageal basal layer of CM group. Mean copy number of CDKN2A and CEP9 and frequency of nuclei with loss of PIK3CA were significantly different in the CM group compared with normal mucosa and marginal levels of deletions in TP63, FHIT, PIK3CA, EGFR, CDKN2A, YES and gains at PIK3CA, TP63, FGFR1, MYC, CDNK2A and NCOA3 were detected in few CM cases, mainly with dilation grades III and IV. All changes occurred at very low levels.Conclusions: Genomic imbalances common in esophageal carcinomas are not present in chagasic megaesophagus suggesting that these features will not be effective markers for risk assessment of ESCC in patients with chagasic megaesophagus.

Flora do delgado em megas chagásicos: estudo pelo teste do H2 respiratório.

The author use the H2 breath test to study the small bowel microflora of chagasic patients with megaesophagus and/or megacolon. Compare this group with a control one. Find a significant increase (P < 0.05) in the small bowel flora of chagasic group. It is concluded that H2 breath is a simple and useful test to detect alteration in intestinal flora.

Biologic and genetics aspects of chagas disease at endemic areas

The etiologic agent of Chagas Disease is the Trypanosoma cruzi, transmitted through blood-sucking insect vectors of the Triatominae subfamily, representing one of the most serious public health concerns in Latin America. There are geographic variations in the prevalence of clinical forms and morbidity of Chagas disease, likely due to genetic variation of the T. cruzi and the host genetic and environmental features. Increasing evidence has supported that inflammatory cytokines and chemokines are responsible for the generation of the inflammatory infiltrate and tissue damage. Moreover, genetic polymorphisms, protein expression levels, and genomic imbalances are associated with disease progression. This paper discusses these key aspects. Large surveys were carried out in Brazil and served as baseline for definition of the control measures adopted. However, Chagas disease is still active, and aspects such as host-parasite interactions, genetic mechanisms of cellular interaction, genetic variability, and tropism need further investigations in the attempt to eradicate the disease. Copyright 2012 Marilanda Ferreira Bellini et al.

The enigmatic role of cholinergic reflex in the pathogenesis of Chagas disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Modelos para dados grupados e sensurados aplicados à área biológica: comparação usando fator de Bayes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)