Navegando por Autor "Rocha, Manoel Otávio da Costa"

Agora exibindo 1 - 9 de 9

Brain natriuretic peptide based strategy to detect left ventricular dysfunction in Chagas disease : a comparison with the conventional approach.
(2006) Ribeiro, Antônio Luiz Pinho; Teixeira, Mauro Martins; Reis, Adelina Martha dos; Silva, André Talvani Pedrosa da; Perez, Amanda Arantes; Barros, Márcio Vinicius Lins; Rocha, Manoel Otávio da Costa
Background: Left ventricular dysfunction (LVd) is the main predictor of mortality in Chagas disease (ChD). Aims: To compare the diagnostic performance of the conventional approach (ECG and chest X-ray) in the recognition of LVd in ChD, with a new strategy, in which BNP is measured in patients with an abnormal ECG. Methods: Consecutive ChD patients recruited at an Outpatient Reference Center in Belo Horizonte, Brazil, without other systemic diseases, in 1998–99 (sample 1, n =165) and in 2001–02 (sample 2, n =62) underwent ECG, chest X-ray, BNP measurement and echocardiography. Results: The prevalence of LVd (ejection fraction _0.40) was 9.1% in the sample 1. The conventional strategy recognized all patients with LVd (sensitivity: 100%, 95% CI: 79.6–100% and negative predictive value _PV 100%, 92.1–100%), but with low specificity (30%, 95% CI: 23.2–37.8) and +PV (12.5%, 95% IC: I7.7–19.6). The BNP/ECG strategy showed significantly better specificity (96.0%, 95% CI: 91.5–98.2, p <0.001) and +PV (66.7%, 95% CI: 43.7–83.7, p <0.001), and non-significantly lower sensitivity (80.0%, 95% CI: 54.8–93.0, p =0.25) and _PV (98.0%,95% CI: 94.2–99.3, p =0.08). Overall accuracy was improved with the new strategy. (94.5%,95% CI: 90.0– 97.1_36.4%, 95% CI: 29.4–43.9, p <0.001). Similar results were obtained for the sample 2. Conclusions: The BNP-based strategy was more accurate than the conventional approach in the detection of LVd in ChD patients and should be considered as a valid option.
Development of an immunogen containing CD4+/CD8+ T‐cell epitopes for the prophylaxis of tegumentary leishmaniasis.
(2022) Ferraz, Isabela de Andrade; Carvalho, Ana Maria Ravena Severino; Brito, Rory Cristiane Fortes de; Roatt, Bruno Mendes; Martins, Vivian Tamietti; Lage, Daniela Pagliara; Cruz, Luiza dos Reis; Medeiros, Fernanda Alvarenga Cardoso; Gonçalves, Denise Utsch; Rocha, Manoel Otávio da Costa; Coelho, Eduardo Antônio Ferraz; Mendes, Tiago Antônio de Oliveira; Duarte, Mariana Costa; Souza, Daniel Menezes
Tegumentary leishmaniasis (TL) is a disease of high severity and incidence in Brazil, and Leishmania braziliensis is its main etiological agent. The inefciency of control measures, such as high toxicity and costs of current treatments and the lack of efective immunoprophylactic strategies, makes the development of vaccines indispensable and imminent. In this light, the present work developed a gene encoding multiple T-cell (CD4+/CD8+) epitope, derived from conserved proteins found in Leishmania species and associated with TL, to generate a chimeric protein (rMEP/TL) and compose a vaccine formulation. For this, six T-cell epitopes were selected by immunoinformatics approaches from proteins present in the amastigote stage and associated with host-parasite interactions. The following formulations were then tested in an L. braziliensis murine infection model: rMEP/TL in saline or associated with MPLA-PHAD®. Our data revealed that, after immunization (three doses; 14-day intervals) and subsequent challenging, rMEP/TL and rMEP/TL+MPLA-vaccinated mice showed an increased production of key immunological biomarkers of protection, such as IgG2a, IgG2a/IgG1, NO, CD4+, and CD8+ T-cells with IFN-γ and TNF-α production, associated with a reduction in CD4+IL-10+ and CD8+IL-10+ T-cells. Vaccines also induced the development of central (CD44highCD62Lhigh) and efector (CD44highCD62Llow) memory of CD4+ and CD8+ T-cells. These fndings, associated with the observation of lower rates of parasite burdens in the vaccinated groups, when compared to the control groups, suggest that immunization with rMEP/TL and, preferably, associated with an adjuvant, may be considered an efective tool to prevent TL.
Effect of pacemaker site on B-type natriuretic peptide levels and left ventricular function in a population with high prevalence of Chagas disease.
(2015) Souza, Sônia Francisca de; Nascimento, Bruno Ramos; Nunes, Maria do Carmo Pereira; Silva, José Luiz Padilha da; Carvalho, Vinícius Tostes de; Beaton, Andrea Z.; Rocha, Manoel Otávio da Costa; Ribeiro, Antônio Luiz Pinho
Functional antibodies against G-protein coupled receptors in Beagle dogs infected with two different strains of Trypanosoma cruzi.
(2022) Wallukat, Gerd; Botoni, Fernando Antônio; Rocha, Manoel Otávio da Costa; Silva, Vitória Louise Teixeira e; Müller, Johannes; Silva, André Talvani Pedrosa da
The interaction of the anti-beta1-adrenergic receptor autoantibodies (b1ARAb) and the anti-muscarinic M2 receptor autoantibodies (M2RAb) with cardiac neurotransmitter receptors were identified in human chronic Chagas cardiomyopathy (CCC) related to the ECG and dysautonomia disturbances. Dogs are considered gold model to the study of Trypanosoma cruzi infection due the clinical similarities with CCC. This study aims to evaluate whether anti- b1ARAb, anti-b2ARAb, and anti-muscarinic M2RAb are generated in Beagle dogs infected by T. cruzi using Y and Berenice-78 strains of T. cruzi. Animals were infected with 4.0 x 103 bloodstream trypomastigotes/kg of body weight and, after 25 months of infection, blood sample was collected, and serum stored at -80°C. Dog serum was treated by ammonium sulphate precipitation and the IgG antibodies isolated and added to the beating neonatal rats’ cardiomyocytes. All T. cruzi-infected dogs developed agonistic b1ARAb, b2ARAb, and M2RAb. Animals infected by Berenice strain presented less b2ARAb and M2RAb activities than dogs infected by Y strain of the parasite. In cardiomyocytes culture, the antibodies recognized an epitope on the second extracellular loop of the receptors which were similar to findings in human Chagas disease. There was no detection of antibody against G protein- coupled receptor in serum from uninfected dogs. In conclusion, both Y and Berenice-78 strains of T. cruzi induced dog antibodies, whose targets located in the second extracellular loop of the adrenergic and muscarinic receptors were similar to those observed in individuals with CCC. Therefore, our findings highlight dogs as a promisor model to investigate pathogenic roles of functional Ab against G-protein coupled receptors.
Highly conserved CDR3 region in circulating CD4(+) Vβ5(+) T cells may be associated with cytotoxic activity in Chagas disease.
(2012) Menezes, Cristiane Alves da Silva; Sullivan, A. K.; Falta, M. T.; Mack, D. G.; Freed, B. M.; Rocha, Manoel Otávio da Costa; Gollob, Kenneth John; Fontenot, A. P.; Dutra, Walderez Ornelas
Human infection with Trypanosoma cruzi leads to Chagas disease, which presents as several different clinical conditions ranging from an asymptomatic form to a severe dilated cardiomyopathy. Several studies have demonstrated that T cells play a critical role in the development of cardiac pathology, as well as in immunoregulation during chronic disease. However, the mechanisms that drive protective or pathogenic T cell response are not known.We have shown that CD4+ T cells from chagasic patients preferentially express T cell receptor (TCR) b-chain variable region (Vb) 5. The aim of this work was to determine whether T cells expressing this particular Vb region displayed variable or restricted CDR3 sequences, as an indicator of the nature of the stimulus leading to the activation of these T cells in vivo. Additionally, we aimed to evaluate phenotypic characteristics of these cells that might be associated with pathology. CDR3 junctional region sequencing of Vb5·1 expressing CD4+ T cells revealed the occurrence of a highly homologous CDR3 region with conserved TCR Jb region usage among patients with cardiac, but not indeterminate, Chagas disease. Moreover, correlation analysis indicated that the frequency of CD4+Vb5·1+ cells is associated with granzyme A expression, suggesting that these cells might display cytotoxic function. Together these results provide new insight into T cell recognition of antigens involved in Chagas disease and suggest that these cells may be implicated in the pathogenesis of chagasic cardiomyopathy.
In vivo inhibitory effect of anti-muscarinic autoantibodies on the parasympathetic function in Chagas disease.
(2010) Ribeiro, Antônio Luiz Pinho; Carvalho, Antônio Carlos Campos de; Lombardi, Federico; Silva, André Talvani Pedrosa da; Teixeira, Mauro Martins; Rocha, Manoel Otávio da Costa
Low levels of vasoactive intestinal peptide are associated with Chagas disease cardiomyopathy.
(2013) Corrêa, Marielle Valério; Rocha, Manoel Otávio da Costa; Sousa, Giovane Rodrigo de; Nunes, Maria do Carmo Pereira; Gollob, Kenneth John; Dutra, Walderez Ornelas; Menezes, Cristiane Alves da Silva
The interconnection between immune and neuroendocrine systems influences regulation of inflammatory responses. The possible relevance that this integrative response may have during the course of Chagas disease remains poorly characterized. In this context, our study was designed to determine the expression of vasoactive intestinal peptide (VIP), a neuropeptide with anti-inflammatory properties, in blood from the indeterminate and cardiac polarized forms of Chagas disease. Moreover, we determined whether the differential expression of VIP is associated with the development of cardiomyopathy in individuals infected with Trypanosoma cruzi. Finally, we analyzed gene polymorphisms of VIP receptors, VPAC1 and VPAC2, and performed correlation analysis of these polymorphisms with the different clinical forms of Chagas disease. Our results demonstrated that low plasma levels of VIP were associated with the cardiac morbidity in Chagas disease. Accordingly, correlation analysis showed that low plasma levels of VIP were associated with worse cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Polymorphism analysis showed a significant association between VPAC1 and the indeterminate form of Chagas disease development. Our data indicate that VIP expression and its receptors’ polymorphism may be important in determining susceptibility to progression from mild to severe forms of Chagas disease.
Plasma concentrations of tumour necrosis factor-alpha, tumour necrosis factor-related apoptosis-inducing ligand, and FasLigand/CD95L in patients with Chagas cardiomyopathy correlate with left ventricular dysfunction.
(2009) Lula, Jamille Fernandes; Rocha, Manoel Otávio da Costa; Nunes, Maria do Carmo Pereira; Ribeiro, Antônio Luiz Pinho; Teixeira, Mauro Martins; Bahia, Maria Terezinha; Silva, André Talvani Pedrosa da
Cardiomyocyte apoptosis is reported to be involved in the pathogenesis of human chronic Chagas cardiomyopathy (CCC). Members of the tumour necrosis factor (TNF) superfamily (TNF-a, FasLigand/CD95L, and TNF-related apoptosis-inducing ligand) are known to activate the death receptor pathway. We therefore investigated whether levels of TNF-a, FasLigand/CD95L, and TRAIL correlated with changes in heart function of patients with Chagas disease (n ¼ 31). Concentrations of TNF-a and TRAIL were clearly augmented in individuals with severe form CCC (n ¼ 16). Levels of FasLigand/CD95L were greater in chagasic patients than in non-infected individuals (n ¼ 15) but did not differentiate between clinical forms of Chagas disease. There was a good correlation between TNF-a (r ¼ 0.85 and r ¼ 0.68, P , 0.0001) or TRAIL (r ¼ 0.68 and r ¼ 0.60, P , 0.001) and left ventricular ejection fraction (LVEF) and left ventricular diastolic diameter (LVDD), respectively. In addition, TNF-a (r ¼ 0.57, P ¼ 0.0001), TRAIL (r ¼ 0.56, P ¼ 0.001), and FasLigand/CD95L (r ¼ 0.51, P ¼ 0.001) showed a good correlation with brain natriuretic peptide, a well-known parameter of ventricular dysfunction in CCC. There was a weak correlation between levels of FasLigand/CD95L (r ¼ 0.50, P , 0.004) and both LVEF and LVDD. There was no correlation between levels of TNF superfamily ligands and chronotropic incompetence, maximal heart rate, or number of ventricular premature beats in 24 h. Plasma levels of TNF superfamily ligands are elevated in patients with functional but not arrhythmogenic disturbances, and these death receptor ligands may be potential markers of ventricular dysfunction in CCC.
Treatment of Chagas cardiomyopathy.
(2013) Botoni, Fernando Antônio; Ribeiro, Antônio Luiz Pinho; Marinho, Carolina Coimbra; Lima, Marcia Maria Oliveira; Nunes, Maria do Carmo Pereira; Rocha, Manoel Otávio da Costa
Chagas’ disease (ChD), caused by the protozoa Trypanosoma cruzi (T. cruzi), was discovered and described by the Brazilian physician Carlos Chagas in 1909. After a century of original description, trypanosomiasis still bringsmuch misery to humanity and is classified as a neglected tropical disease prevalent in underdeveloped countries, particularly in South America. It is an increasing worldwide problem due to the number of cases in endemic areas and the migration of infected subjects tomore developed regions, mainly North America and Europe. Despite its importance, chronic chagas cardiomyopathy (CCC) pathophysiology is yet poorly understood, and independently of its social, clinical, and epidemiological importance, the therapeutic approach of CCC is still transposed from the knowledge acquired from other cardiomyopathies. Therefore, the objective of this review is to describe the treatment of Chagas cardiomyopathy with emphasis on its peculiarities.