Differences in resistance to reinfection with low and high inocula of <i>Trypanosoma cruzi</i> in chagasic mice treated with nifurtimox and relation to immune response

Reinfection of chronic chagasic mice after treatment with nifurtimox resulted in different outcomes according to the number of parasites used for inoculation. Nifurtimox-treated chagasic animals injected with 2,500 trypomastigotes developed higher parasitemia and increased mortality compared with nontreated chagasic mice. When reinfection was done with 25 trypomastigotes, treated and nontreated animals showed similar parasitemias and mortalities, which were significantly higher in nonchagasic controls infected for the first time. Immunological studies showed that treatment with nifurtimox led to a decrease in anti-Trypanosoma cruzi antibodies engaged in parasite destruction, inducing either complement-dependent lysis or antibodydependent cytotoxicity, but no difference in anti-T. cruzi cell-mediated immunity was found between treated and nontreated chagasic animals. It is concluded that treatment with nifurtimox leads to a loss of resistance to reinfection with a large number of trypanosomes, which is maintained with challenge with a few parasites, and that these two thresholds of premunition are probably associated with humoral and cell-mediated anti-T. cruzi immune responses, respectively.Facultad de Ciencias Médica

Presence of anti-<i>Trypanosoma cruzi</i> antibodies in the sera of mice with experimental autoimmune myocarditis

The existence of antigens shared in common by T. cruzi and heart muscle cells is suggested by the presence of antibodies binding to the parasite surface in the serum of mice with autoimmune myocarditis induced by immunization with syngeneic heart antigens.Facultad de Ciencias Médica

DNA content and expression of cell cycle proteins in caterpillar nuclei from fetal human cardiac myocytes

Caterpillar nuclei (CN) are characterized by their peculiar morphology, with chromatin distributed in clusters and running along the longitudinal axis of the nucleus. They can be observed in normal hearts of fetuses as well as in hearts of children and adults with rheumatic heart disease. This study has demonstrated by means of ploidy studies with digital image analysis that in the fetal heart (20.5±1.8 weeks) the CN (diploid = 5.6±8.4%; tetraploid = 46.2±24.2%; hypertetraploid = 46.9±26.3%) present higher DNA content than non-caterpillar myocyte nuclei (diploid = 89.4±6.2%; tetraploid = 10.0±4.1%; hypertetraploid = 1.5±1.3%) (P=0.000001, 0.00013, and 0.000038, respectively). Expression of proliferation cell nuclear antigen (PCNA; 30.6±11.7% in CN and 13.4±7.3% in non-caterpillar myocyte nuclei; P=0.0115) and cyclin B1 (2.8±3.8% and 12.6±15.6%, respectively; P=n.s.) was also positive in these nuclei. In conclusion, these results suggest that there exists a relationship between CN morphology and myocyte replication phenomena.Universidad Nacional de La Plat

Acentuación de la enfermedad experimental de injerto contra huésped con el agregado de esplenocitos murinos

En un trabajo anterior se presentó en un modelo de Enfermedad de Rechazo de Injerto vs Huésped (EICH) en ratones ablacionados con ciclofosfamida y trasplantados con células de médula ósea con hemi-disparidad genética una alteración del ciclo celular, con detención en la fase G2-M de las células del epitelio intestinal y de la piel de ratones, asociada a un aumento de la apoptosis. Con el fin de intentar profundizar en los mecanismos de producción de daño epitelial en la EICH se modificó el modelo mediante el agregado de células provenientes del bazo.Facultad de Ciencias Médicas (FCM

Asociación de la detención del ciclo celular en la fase g2-m con la apoptosis en la enfermedad experimental del injerto contra huésped

El objetivo de este artículo es pesquisar en un modelo experimental de EICH, si en las células de los epitelios de la piel y tubo digestivo existen alteraciones en la expresión de proteínas involucradas en el ciclo celular que se asocien con la presencia de apoptosis.Facultad de Ciencias Médicas (FCM

Differences in resistance to reinfection with low and high inocula of <i>Trypanosoma cruzi</i> in chagasic mice treated with nifurtimox and relation to immune response

Reinfection of chronic chagasic mice after treatment with nifurtimox resulted in different outcomes according to the number of parasites used for inoculation. Nifurtimox-treated chagasic animals injected with 2,500 trypomastigotes developed higher parasitemia and increased mortality compared with nontreated chagasic mice. When reinfection was done with 25 trypomastigotes, treated and nontreated animals showed similar parasitemias and mortalities, which were significantly higher in nonchagasic controls infected for the first time. Immunological studies showed that treatment with nifurtimox led to a decrease in anti-Trypanosoma cruzi antibodies engaged in parasite destruction, inducing either complement-dependent lysis or antibodydependent cytotoxicity, but no difference in anti-T. cruzi cell-mediated immunity was found between treated and nontreated chagasic animals. It is concluded that treatment with nifurtimox leads to a loss of resistance to reinfection with a large number of trypanosomes, which is maintained with challenge with a few parasites, and that these two thresholds of premunition are probably associated with humoral and cell-mediated anti-T. cruzi immune responses, respectively.Facultad de Ciencias Médica

Selectivity of alterations in skeletal fibers in chronic Chagas' disease of the mouse

In mice chronically infected withTrypanosoma cruzi, the masseter muscle (rich in type II fibers) was devoid of inflammatory infiltrates and parasites. In contrast, other muscles, composed of type I and II fibers, showed a decrease of type I fibers, parasites and lesions, suggesting that inT. cruzi infection type I muscle fibers are selectively damaged.Facultad de Ciencias Médica

Presencia de angiogénesis en placas vulnerables ateroscleróticas en corazones humanos aparentemente sanos

Background Angiogenesis or neovascularization involves the formation of new blood vessels adjacent to preexisting vessels. This vascular proliferation is prevalent in various clinical conditions, such as atherosclerosis. Microvessels in coronary artery atherosclerotic plaques may contribute to plaque instability. Objectives The aim of this study was to correlate the presence of angiogenesis in atherosclerotic plaques with the criteria of plaque vulnerability used by the American Heart Association (AHA). Methods One hundred and twenty one hearts from non-diabetic and apparently healthy transplant donors older than 40 years were selected. The coronary arteries were examined and all areas of cross-sectional luminal narrowing underwent histological, immunohistochemical and morphometric studies. A semi-quantitative score (scale 0-3) was used to identify of angiogenesis. Univariate and multivariate logistic regression analysis was performed to identify angiogenesis-related risk factors. Results On hundred and forty three high-risk lesions (AHA type IV, V and VI) in the left anterior descending coronary artery (46.3%), the circumflex coronary artery (28.9%) and the right coronary artery (43%) were identified. Angiogenesis had a statistically significant association with the severity of vascular occlusion, inflammatory cell infiltration, presence of a lipid core, fibrosis and periarteritis. A history of hypertension (HT) was associated with angiogenesis only in lesions of the left anterior descending coronary artery (LAD). According to the AHA classification angiogenesis was detected in 1 Type II, 5 Type III, 21 Type IV, 22 Type V, and 7 Type VI plaques. Conclusions Angiogenesis in vulnerable plaques was associated with the severity of vascular occlusion, inflammatory cell infiltration, fibrosis and presence of a lipid core, and with a history of HT in LAD lesions. There was no association between angiogenesis and plaque hemorrhage or calcification, suggesting that angiogenesis may anticipate plaque rupture.Introducción La angiogénesis o neovascularización involucra la formación de nuevos conductos en las adyacencias de vasos preexistentes. Esta proliferación vascular es frecuente en varias circunstancias clínicas, como es el caso de la aterosclerosis. Los microvasos de las placas ateroscleróticas coronarias pueden estar vinculados a la inestabilidad de la lesión. Objetivo Correlacionar la presencia de angiogénesis en placas ateroscleróticas con los criterios de vulnerabilidad de la clasificación de la American Heart Association (AHA). Material y métodos En 121 corazones de donantes no diabéticos aparentemente sanos y mayores de 40 años destinados para homoinjertos se examinaron las arterias coronarias y todas las áreas de estrechamiento luminal se sometieron a estudios histológicos, inmunohistoquímicos y morfométricos. Para el análisis de la angiogénesis se empleó un puntaje semicuantitativo (escala 0-3). Se realizó un análisis de regresión logística univariado y multivariado para identificar factores de riesgo relacionados con la angiogénesis. Resultados Se hallaron 143 lesiones de riesgo alto (AHA tipos IV, V y VI) en las arterias descendente anterior (46,3%), circunfleja (28,9%) y coronaria derecha (43%). La angiogénesis se asoció en forma estadísticamente significativa con el grado de oclusión vascular, la infiltración de células inflamatorias, la presencia de centro lipídico, la fibrosis, la periarteritis y, sólo en la descendente anterior, con el antecedente de hipertensión arterial (p < 0,006). Se detectó angiogénesis en 1 placa tipo II, en 5 tipo III, en 21 tipo IV, en 22 tipo V y en 7 placas tipo VI (AHA). Conclusiones La angiogénesis de placas vulnerables se asoció con el grado de oclusión vascular, la infiltración de células inflamatorias, la fibrosis, la presencia de núcleo lipídico y, sólo en la descendente anterior, con el antecedente de hipertensión arterial. No se encontró asociación con la hemorragia intraplaca o la calcificación, lo cual sugiere que la angiogénesis puede anticipar la rotura de las placas