A importância do diagnóstico por imagem na classificação dos endoleaks como complicação do tratamento endovascular de aneurismas aórticos

OBJETIVO: Relatar uma série de casos de endoleaks, com descrição da classificação vigente. MATERIAIS E MÉTODOS: Realizou-se um estudo retrospectivo dos endoleaks diagnosticados em nossa instituição, entre 2005 e 2009. Foram incluídos 20 casos, utilizados para ilustrar os diferentes tipos de endoleaks. RESULTADOS: Setenta por cento dos pacientes eram do sexo masculino. A idade variou entre 43 e 91 anos, média de 76,3 anos. Treze casos foram observados na aorta abdominal infrarrenal, quatro na aorta torácica, dois nas artérias ilíacas e um no território carotídeo. A ultrassonografia foi o método utilizado para o diagnóstico em 3 casos e a tomografia computadorizada, nos outros 17 casos. Classificação: tipo I, 60%; tipo II, 25%; tipo III, 15%. Não foram observados os demais tipos nesta série. CONCLUSÃO: O diagnóstico precoce e a correta classificação são fundamentais para o manejo adequado dos casos de endoleaks, tornando o conhecimento de seus subtipos conceito fundamental na formação do médico especialista em radiologia e diagnóstico por imagem e para o cirurgião vascular.

Desenvolvimento de método analítico por CLAE em comprimidos de Benznidazol para a Doença de Chagas

The analytical method of high performance liquid chromatography (HPLC) for the assay of benznidazole in tablets was developed and validated following the requirements of regulatory agencies. The method used as mobile phase acetonitrile:wather 1:1, a C18 column of 12.5 cm length x 4 mm id, 5 mm particles and lambda=316 nm. The statistical analysis of the results demonstrated that the method satisfies all parameters so as to be considered a safe and efficient analytical alternative of low cost for laboratory routine.

Quimioterapia da doença de Chagas: estado da arte e perspectivas no desenvolvimento de novos fármacos

Neglected diseases are a major global cause of illness, long-term disability and death. Chagas' disease is a parasitic infection widely distributed throughout Latin America, with devastating consequences in terms of human morbidity and mortality. The existing drug therapy suffers from a combination of drawbacks including poor efficacy, resistance and serious side effects. In 2009, we celebrate the 100th anniversary of the discovery of Chagas' disease, facing the challenges of developing new, safe and effective drugs for the treatment of this disease. This brief review attempts to highlight the state of the art, limitations and perspectives of Chagas' disease drug development.

Flavonoides e terpenoides de Croton muscicarpa (Euphorbiaceae)

A new sesquiterpene and twelve known compounds comprising eight flavonoids and four terpenoids, were isolated from the leaves, stems, roots and exudate of Croton muscicarpa Müll. Arg.. Their structures were identified as the terpenoids 6α-methoxy-cyperene, dammaradienol, squalene, acetyl aleuritolic acid and spathulenol, and as the flavonoids retusin, 3,7,4'-trimethoxy kaempferol, ombuine, pachipodol, kaempferol, casticin, 5-hydroxy-3,6,7,4'-tetramethoxyflavone and artemetin. All isolated compounds were characterized based on IR, MS, ¹H and 13C NMR, including 2D analyses (COSY, HSQC, HMBC, NOESY) and comparison with data from the literature.

Estudo eletromanométrico do esôfago em portadores da doença de Chagas em sua forma indeterminada

OBJETIVOS: Avaliar as alterações manométricas dos esfíncteres superior (ESE) e inferior do esôfago, bem como a motilidade de seu corpo, em pacientes com a forma indeterminada da Doença de Chagas. MÉTODO: Foram considerados 37 pacientes portadores da Doença de Chagas, assintomáticos, que apresentavam eletrocardiograma, enema opaco e radiografia contrastada do esôfago sem alterações características da doença (forma indeterminada). Estes foram submetidos à eletromanometria do esôfago em que foram analisados dados sobre a pressão dos esfíncteres e ondas peristálticas do corpo do esôfago. RESULTADOS: Detectouse uma diminuição da média da amplitude de contração do corpo do esôfago (p=0,03) nos portadores de ondas sincrônicas quando comparados com os portadores de ondas assincrônicas. A comparação da média das pressões máximas do ESE nos pacientes portadores de ondas sincrônicas foi significativamente maior (p= 0,02) que a média encontrada nos portadores de ondas assincrônicas. CONCLUSÃO: Encontrou-se um elevado número (48,65%) de portadores de ondas sincrônicas em pacientes com a forma indeterminada da Doença de Chagas; notou-se uma redução da média da amplitude da contração do corpo do esôfago em portadores de ondas sincrônicas e observou-se que a média das pressões máximas do ESE é maior nos pacientes com ondas sincrônicas (207,14 mmHg) quando comparada com os portadores de ondas assincrônicas (142,44 mmHg). Dessa forma propomos uma discussão sobre a classificação atual da Doença de Chagas.

Formas digestivas da doença de Chagas e carcinogênese: um estudo de associação

Os autores analisam a relação entre carcinogênese gastrintestinal e doença de Chagas, com base em revisão pormenorizada da literatura. Para tal, foram selecionados estudos epidemiológicos, experimentais e de descrição anatomopatológica com material humano. O artigo discute a possibilidade de a proteção ser conferida por fatores celulares morfocinéticos, imunológicos e neuroendócrinos não totalmente conhecidos e que seriam secundários à degeneração plexular. Também são apresentados aspectos relacionados à interação parasito-hospedeiro, sob o ponto de vista da modulação epitelial da mucosa colônica, e suas implicações antitumorais. Por fim, expõe-se o mecanismo fisiopatológico de desenvolvimento da neoplasia de esôfago em pacientes com megaesôfago. Conclui-se que a colopatia chagásica, especialmente o dano neuronal intrínseco, constitui modelo de estudo que pode contribuir no entendimento da carcinogênese colorretal.

Aspectos epidemiológicos da Doença de Chagas canina no semiárido paraibano

Com o objetivo de determinar os aspectos epidemiológicos que envolvem a doença de Chagas (DC) canina e identificar os principais fatores de risco da enfermidade no semiárido paraibano, foi conduzido um estudo na zona rural de Patos, onde a área foi dividida em três estratos amostrais (Norte, Sul e Oeste) e, em cada estrato foram amostradas aleatoriamente 294 casas, e dessas todos os cães domiciliados representaram as unidades elementares do estudo. Em cada unidade domiciliar foi aplicado um questionário epidemiológico para se obter informações sobre indicadores que favorecem a disseminação da doença no segmento peridomiciliar. O diagnóstico sorológico para DC em cães foi baseado em três métodos (RIFI, ELISA e HAI), sendo consideradas positivas aquelas amostras que apresentassem pelo menos dois testes reagentes e ausência de reatividade cruzada. Para zona rural do município, a prevalência de cães sororreagentes para T. cruzi por estrato amostral foram: Norte 6,05%, Sul 3,59% e Oeste 2,97%, correspondendo a uma prevalência em sua totalidade de 4,08%. Os fatores de riscos (odds ratio, OR) evidenciados em análise multifatorial foram: tipo de parede (OR=2,59 [1,24-5,4]), presença de armazém (OR=1,89 [1,31-3,0]), presença de galinheiros (OR=8,31 [1,29-61,7]), contato com animais (OR=9,11 [1,12-73,9]), contato com aves (OR=9,7 [1,81-52,83]), triatomíneos capturados (OR=16,58 [3,43-80,23]) e antropismo (OR=4,35 [1,36-14,0]. Diante dos resultados foi possível se obter informações inerentes à situação epidemiológica da Doença de Chagas ressaltando características biogeográficas da zona rural do semiárido paraibano, elevando a espécie canina e os fatores de risco evidenciados, em destaque ao contato com aves e ecótopos artificiais, operacionalizando indicadores a serem assistidos e considerados na cadeia de transmissão da doença na região.

Cytokine profiles during experimental Chagas' disease

People infected with Trypanosoma cruzi remain so for life, yet only 30-40% of these individuals develop characteristic chagasic cardiomyopathies. Similarly, when infected with the Brazilian strain of T. cruzi, DBA/2 mice develop severe cardiac damage while B10.D2 mice do not. To better understand the immunological parameters that may be involved in the disease process, we have used this murine model (DBA/2 vs B10.D2) and compared the changes in cytokine production during the course of infection with T. cruzi. Concanavalin A (Con A) stimulation of spleen cells harvested during the acute phase (day 30) resulted in similarly high levels of IFN-g in both mouse strains. However, the amount of IFN-g in supernatants from cultures of B10.D2 spleen cells initiated during the chronic phase (day 72) was at subacute levels, whereas secretion by chronic DBA/2 spleen cells remained high. In addition, Con A-stimulated spleen cells from acute DBA/2 mice produced approximately twice as much IL-10 and significantly more IL-4 than cells from B10.D2 mice. IL-4 secretion remained low by cells from chronic B10.D2 mice, but when using cells from chronic DBA/2 mice, levels continued to increase beyond the already high levels secreted by cells harvested during the acute phase. Proliferative responses to Con A stimulation by spleen cells from DBA/2 mice were significantly higher than those from B10.D2 mice in both the acute and chronic phases. These data suggest that enhanced responses in DBA/2 mice, which may be related to a higher parasite burden, a lack of down-regulation, and/or the onset of autoimmune phenomena, correlate with the more severe cardiomyopathy seen in pathopermissive mice.

IFN-g in human Chagas' disease: protection or pathology?

An apparently paradoxical role for IFN-g in human Chagas' disease was observed when studying the pattern of cytokine production by peripheral blood mononuclear cells (PBMC) obtained from two groups of chagasic patients after specific stimulation with Trypanosoma cruzi-derived antigens. The groups studied were 1) patients treated with benznidazole during the acute phase of Trypanosoma cruzi infection and 2) chronically infected untreated patients. In the treated group, higher levels of IFN-g were produced by PBMC from individuals cured after treatment when compared to non-cured patients. In contrast, in the chronically infected group (not treated) higher levels of IFN-g were produced by PBMC from cardiac patients in comparison with asymptomatic (indeterminate) patients. This apparently paradoxical role for IFN-g in human Chagas' disease is discussed in terms of the possibility of a temporal difference in IFN-g production during the initial stages of the infection (acute phase) in the presence or absence of chemotherapy. The maintenance of an immune response with high levels of IFN-g production during the chronic phase of the infection may favor cure or influence the development of the cardiac form of the disease

Cytokine production profile of heart-infiltrating T cells in Chagas' disease cardiomyopathy

The hallmark of chronic Chagas' disease cardiomyopathy (CCC) is the finding of a T cell-rich inflammatory mononuclear cell infiltrate in the presence of extremely few parasites in the heart lesions. The scarcity of parasites in affected heart tissue casts doubt on the direct participation of Trypanosoma cruzi in CCC heart tissue lesions, and suggests the possible involvement of autoimmunity. The cells in the infiltrate are presumably the ultimate effectors of tissue damage, and there is evidence that such cells recognize cardiac myosin in molecular mimicry with T. cruzi proteins rather than primary reactivity to T. cruzi antigens (Cunha-Neto et al. (1996) Journal of Clinical Investigation, 98: 1709-1712). Recently, we have studied heart-infiltrating T cells at the functional level. In this short review we summarize the studies about the role of cytokines in human and experimental T. cruzi infection, along with our data on heart-infiltrating T cells in human Chagas' cardiomyopathy. The bulk of evidence points to a significant production of IFN-g and TNF-a which may be linked to T. cruzi-induced IL-12 production

Total and segmental colonic transit time in constipated patients with Chagas’ disease without megaesophagus or megacolon

Manometric and pharmacological tests have shown that motor abnormalities may occur in the non-dilated colons of chagasic patients. In order to investigate the presence of abnormalities of colonic function in constipated patients with Chagas’ disease (ChC) without megaesophagus or megacolon, studies of total and segmental colonic transit time with radiopaque markers were performed on 15 ChC patients, 27 healthy volunteers and 17 patients with idiopathic constipation (IC). The values obtained for the control group were similar to those reported in the literature (total colonic time: 34.1 ± 15.6 h; right colon: 9.9 ± 7.3 h; left colon: 10.8 ± 10 h, and rectosigmoid: 12.6 ± 9.9 h). Colonic transit time data permitted us to divide both IC and ChC patients into groups with normal transit and those with slow colonic transit. Colonic inertia was detected in 41% of IC patients and in 13% of ChC patients; left colon isolated stasis (hindgut dysfunction) was detected in 12% of IC patients and 7% of ChC patients, and outlet obstruction was detected in 6% of IC patients and 7% of ChC patients. There were no significant differences in total or segmental colonic transit times between slow transit IC and slow transit ChC patients. In conclusion, an impairment of colonic motility was detected in about 30% of constipated patients with Chagas’ disease without megaesophagus or megacolon. This subgroup of patients presented no distinctive clinical feature or pattern of colonic dysmotility when compared to patients with slow transit idiopathic constipation.

Upper esophageal sphincter pressure in patients with Chagas' disease and primary achalasia

The most important component of the upper esophageal sphincter (UES) is the cricopharyngeal muscle. During the measurement of sphincter pressure the catheter passed through the sphincter affects the pressure value. In Chagas' disease and primary achalasia there is an esophageal myenteric plexus denervation which may affect UES pressure. We measured the UES pressure of 115 patients with Chagas' disease, 28 patients with primary achalasia and 40 healthy volunteers. We used a round manometric catheter with continuous perfusion and the rapid pull-through method, performed in triplicate during apnea. Pressures were measured in four directions, and the direction with the highest pressure (anterior/posterior) and the average of the four directions were measured. The highest UES pressure in Chagas' disease patients without abnormalities upon radiologic esophageal examination (N = 63) was higher than in normal volunteers (142.8 ± 47.4 mmHg vs 113.0 ± 46.0 mmHg, mean ± SD, P<0.05). There was no difference in UES pressure between patients with primary achalasia and patients with Chagas' disease and similar esophageal involvement and normal volunteers (P>0.05). There was no difference between patients with or without esophageal dilation. In the group of subjects less than 50 years of age the UES pressure of primary achalasia (N = 21) was lower than that of Chagas' disease patients with normal radiologic esophageal examination (N = 41), measured at the site with the highest pressure (109.3 ± 31.5 mmHg vs 149.6 ± 45.3 mmHg, P<0.01) and as the average of the four directions (64.2 ± 17.1 mmHg vs 83.5 ± 28.6 mmHg, P<0.05). We conclude that there is no difference in UES pressure between patients with Chagas' disease, primary achalasia and normal volunteers, except for patients with minor involvement by Chagas' disease, for whom the UES pressure at the site with the highest pressure was higher than the pressure of normal volunteers and patients with primary achalasia.

Esophageal striated muscle contractions in patients with Chagas' disease and idiopathic achalasia

Chagas' disease causes degeneration and reduction of the number of intrinsic neurons of the esophageal myenteric plexus, with consequent absent or partial lower esophageal sphincter relaxation and loss of peristalsis in the esophageal body. The impairment of esophageal motility is seen mainly in the distal smooth muscle region. There is no study about esophageal striated muscle contractions in the disease. In 81 patients with heartburn (44 with esophagitis) taken as controls, 51 patients with Chagas' disease (21 with esophageal dilatation) and 18 patients with idiopathic achalasia (11 with esophageal dilatation) we studied the amplitude, duration and area under the curve of esophageal proximal contractions. Using the manometric method and a continuous perfusion system we measured the esophageal striated muscle contractions 2 to 3 cm below the upper esophageal sphincter after swallows of a 5-ml bolus of water. There was no significant difference in striated muscle contractions between patients with heartburn and esophagitis and patients with heartburn without esophagitis. There was also no significant difference between patients with heartburn younger or older than 50 years or between men and women or in esophageal striated muscle contractions between patients with heartburn and Chagas' disease. The esophageal proximal amplitude of contractions was lower in patients with idiopathic achalasia than in patients with heartburn. In patients with Chagas' disease there was no significant difference between patients with esophageal dilatation and patients with normal esophageal diameter. Esophageal striated muscle contractions in patients with Chagas' disease have the same amplitude and duration as seen in patients with heartburn. Patients with idiopathic achalasia have a lower amplitude of contraction than patients with heartburn.

Minor segmental wall motion abnormalities detected in patients with Chagas' disease have adverse prognostic implications

Recent data from our laboratory have shown that patients with the indeterminate form of Chagas' disease can have impairment of left ventricular contractility, as evaluated by the slope of the left ventricle end-systolic pressure-dimension relationship. We also showed that Chagas' disease patients with minimal baseline wall motion abnormalities detected by two-dimensional echocardiography have more intense contractility impairment when compared to patients with the indeterminate form of the disease without this abnormality. The prognostic implications of these findings have not been established. We evaluated 59 patients (37-76 years, mean = 55 years) with different clinical forms of Chagas' disease, who had normal left ventricular global systolic function at baseline (57.6 ± 6.9%) and who had at least one additional echo during clinical follow-up (0.4-17.6; mean 4.6 years). Group 1 consisted of 14 patients with minor baseline left ventricle wall motion abnormalities and group 2 consisted of 45 patients without these abnormalities. During follow-up, global left ventricle systolic function deterioration was observed in 10 group 1 patients (71.4%) and in only 10 group 2 patients (22.2%; P < 0.005). Age and duration of follow-up were not independent determinants of left ventricular function deterioration in these patients. The present data indicate that mild segmental left ventricular wall motion abnormalities are associated with worsening of systolic function in Chagas' disease patients who have normal baseline global systolic performance.

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

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.