Blood viscosity changes in experimentally Trypanosoma cruzi-infected rats.

Microcirculatory alterations would explain focal lesions found in Chagas' cardiomyopathy. Trypanosoma cruzi (T. cruzi) infection induces host blood properties modifications and defensive responses capable of producing blood hyperviscosity, an ischemic risk factor able to affect microvascular blood flow. We studied whole blood viscosity (eta(b)) and plasmatic and cellular factors influencing it in rats, 7 and 14 days after experimental infection with T. cruzi. Increased plasma viscosity (eta(p)) was found in infected versus control rats and it was correlated with high blood parasite levels at 7 days and enhanced gamma-globulin fraction concentration at 14 days. The hematocrit, mean corpuscular volume (MCV) and eta(b) were higher in 14 days infected rats vs. 7 days and control animals. Also, electron microscopy observation showed morphological changes in red blood cells (RBC) at 7 and 14 days post-infection, with increased proportion of echinocyte and stomatocyte shapes transformation. In our rat model of Chagas' disease, BPL, increased plasmatic protein concentration, enhanced MCV and RBC shapes transformation would determine blood hyperviscosity, cause of microvascular blood flow abnormalities.

Metronomic therapy with cyclophosphamide induces rat lymphoma and sarcoma regression, and is devoid of toxicity.

BACKGROUND: Our aim was to investigate the clinical efficacy and toxicity of metronomic administration of low-dose cyclophosphamide (Cy) in lymphoma and sarcoma rat tumour models. METHODS: Adult inbred rats were challenged with lymphoma TACB and sarcoma E100 s.c. on day 0. Animals were divided into two groups: group I, control, injected with saline three times a week; and group II, treated with Cy 10 mg/kg three times a week, from day 10 until the tumour was non-palpable, or 5 mg/kg three times a week from day 7. Tumours were measured and animals were weighed twice weekly. Periodic blood samples were taken for determination of urea, creatinine, serum glutamic-oxaloacetic transaminase, lactate dehydrogenase and haematological parameters. RESULTS: The administration of low-dose Cy eradicated established rat lymphomas and sarcomas; there was neither metastatic growth nor recurrence at primary sites for 100% of the lymphomas and 83% of the sarcomas. In addition, the treatment did not cause weight loss, and was devoid of haematological, cardiac, hepatic and renal toxicity. CONCLUSIONS: Metronomic administration of Cy at low doses on a thrice weekly schedule to already grown rat lymphomas and sarcomas demonstrated itself to be a successful antitumour therapy that did not cause weight loss and was devoid of haematological, cardiac, hepatic and renal toxicity.

Electrocardiographic alterations in chronically Trypanosoma cruzi-infected persons exposed to cardiovascular factors.

METHODS: We analyzed the potential influence that associated risk factors (ARF), such as smoking, alcoholism, overweight, and hypertension, could have on the establishment of chronic chagasic cardiomyopathy (CC). The sample was comprised of 124 individuals, 69 males and 55 females (mean age +/- SD, 41 +/- 9.5 years), who were born in en demic areas of Northern Argentina and migrated further to Rosario City, an area where autochthonous cases of Chagas' disease have never been registered. Assessments included the following: clinical examination to discard previous cardiomyopathies; search for the presence of ARF according to standard criteria; specific serology; frontal chest X-ray, and 12-lead resting electrocardiogram (ECG). Subjects were classified on the basis of their serological status and presence of ARF into four groups: Tc+ARF+ T. cruzi-infected persons with ARF (n = 41); Tc-ARF+ seronegativity in presence of ARF (n = 27); Tc+ARF- individuals showing positive serology that lacked ARF (n = 27), and Tc-ARF- seronegative individuals having no ARF (n = 29). RESULTS: Except for a higher female/male ratio in groups presenting no ARF (p < 0.02), no statistical differences as to age, length of residence in endemicity areas (LR), and ARF distribution were recorded among groups. Forty-one persons presented abnormal ECG tracings, distributed thus: Tc+ARF+, 18/41; Tc-ARF+, 14/27, Tc+ARF-, 14/27, and Tc-ARF, 4/29 (p < 0.01, in relation to the latter group). Subjects from the Tc+ARF+, Tc-ARF+, and Tc+ARF- groups had 4.89-, 6.7-, and 6.7-fold increases, respectively, if having an abnormal ECG when compared with Tc-ARF- individuals. Comparisons on the frequency of abnormal ECG between seropositives carrying ARF or not yielded a non-significant odds ratio, be it estimated as crude, or after adjusting for sex, age, and LR in multivariate analysis. CONCLUSIONS: Presence of ARF was not associated with an increasing risk of cardiac affectation in chronically T. cruzi-infected persons, but resulted in chagasic-compatible ECG abnormalities in those seronegative individuals.

Electrocardiographic alteration among first degree relatives with serologic evidence of Trypanosoma cruzi infection. A sibship study.

To analyze whether electrocardiographic alterations (ECGA) in patients with antibodies to Trypanosoma cruzi showed a pattern of familial aggregation, a sample of 379 young adults (166 men and 213 women) distributed in sibships, were assessed for the presence of anti-T. cruzi antibodies, and subjected to a complete clinical examination and a standard resting electrocardiogram (ECG). Positive T. cruzi serology was detected in 165 individuals, 48 of them showing an abnormal ECG (overall prevalence 29%). One hundred and eleven seropositive individuals were distributed in 45 sibships, each of them constituted by more than one seropositive sib, with ECGA being present in 34 out of these patients. Seropositive subjects with ECGA were detected in 27 sibships. Since the index case within each sibship is counted exactly once, affected individuals selected at random as propositi were extracted to calculate the prevalence of ECGA among first degree relatives of probands. Abnormal ECGs were recorded in 7 out of 45 sibs yielding a prevalence that did not differ from estimations registered in the general population or seropositive sibs. Data from the present sample show no familial aggregation for the occurrence of ECGA in patients with T. cruzi. infection.

Efecto de la reinfeccion sobre la evalucion de ratas infectadas con Trypanosoma cruzi / Effect of reinfection on the evolution of rats infected with Trypanosoma cruzi

El objetivo de este trabajo fue comprobar si una de las variables medio-ambientales, la reinfeccion, puede modificar el comportamiento observado en un modelo de rata a nivel de parasitemia, anticuerpos sericos, manifestaciones electrocardiograficas y/o lesion miocardica. Los grupos experimentales fueron: GI: ratas infectadas al destete com 1 x "10 POT 6" T. cruzi; GR: igual a GI mas reinfecciones cada 30 dias hasta los 150 dias post-infeccion inicial (p.i.i.); "GI IND 1". Los xenodiagnosticos fueron negativos en los tres grupos. Los anticuerpos sericos no se modificaron significativamente en GR respecto de GI, salvo en los anticuerpos 7S, pues los del GR presentaron titulos superiores en algunos de los dias estudiados. Los ECG basales no mostraron cambios distintivos en las ratas infectadas. La pruieba de ajmalina mostro una disminucion de la FC independiente del tratamiento; el PR, QaT y QRS se prolongaron significativamente en todos los grupos respecto del basal (p < 0.05), salvo el QaT en el GT; ademas el cambio de PR y QaT fue mayor en los infectados (p < 0.05). En los grupos infectados hubo tambien una amplia variacion en la orientacion del eje electrico respecto del valor basal, acompanado de cambios morfologicos mas manifiestos emGR. La proporcion de lesion cardiaca detectada histologicamente en los grupos

[Effect of reinfection on the development of rats infected with Trypanosoma cruzi]. / Efecto de la reinfección sobre la evolución de ratas infectadas con Trypanosoma cruzi.

The present study was undertaken in order to demonstrate that reinfection could modify parasitemia, serum antibodies, electrocardiographic patterns and/or myocardial lesions already observed in a rat model. Experimental groups IG: rats infected at weaning with 1 x 10(6) T. cruzi; RG: same as IG plus reinoculations each 30 days until completion on day 150; IG1: 51 day old infected rats; C: controls. A high parasitemia was detected in IG and RG until day 20 showing a tendency to become negative on day 30. No parasites were observed in RG after the first reinoculation which could not be attributed to the old age of the host since there was no parasitemia in IG1. Xenodiagnosis were negative in all three groups. Serum antibodies were not significantly modified in RG in comparison with IG, except for 7S antibodies, since RG showed higher titres in some days under study. No distinct patterns of basal ECG were observed in infected rats. The ajmaline test reduced the heart rate (HR) showing no treatment dependence. The PR, QaT and QRS were significantly lengthened in all groups regarding the basal one (p less than 0.05), except for the QaT in C. Besides, the PR and QaT alterations were greater in the infected rats (p less than 0.05). There was also present a wide variety of electric axis orientations, regarding the basal value, accompanied by morphological changes more evident in the RG. The incidence of cardiac lesions histologically detected in the infected group was significantly higher than in C (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Influencia de la edad de la rata en la evolución de la infección com trypanosoma cruzi / Influence of the age of the rat on the course of infection with trypanosoma cruzi

En la primera parte de este trabajo se estudió en la fase aguda, la parasitemia y respuesta inmune humoral específica, en ratas de línea "1", inoculadas al destete con 1x10**6 T. cruzi vivos de la cepa Tulahuén (GD), y adultos jóvenes con 1x10**6 T. cruzi (GA) y con 7x10**6 T. cruzi, cantidad equivalente a la inoculada en los destetes según peso (GA-1). La parasitemia fue significativamente mayor en el GD que en los GA y GA-1. Por otro lado, el GD presentó bajos títulos de anticuerpos, en relación a los adultos con ambas concentraciones de T. cruzi, que tuvieron un comportamiento similar. En el período crónico se evaluaron, a los 180 días post-infección, los ECG y la histolatología de corazón en animales al destete y adultos, con sólo 1x10**6 T. cruzi. La frecuencia cardíaca en los animales infectados fue mayor que la de los testigos. La proporción de lesión cardíaca (miocarditis, pericarditis y/o fibrosis) fue superior en el GD y en el GA, con respecto al GT, y el GA presentó un 35,6% de fibrosis, significativamente diferente de los otros grupos. La lesión fue sobre todo leve, ventricular y no se visualizaron parásitos in situ. En síntesis, en la rata, en la fase aguda de la infección, se encontraron diferencias marcadas en serología y parasitemia según la edad del huésped; sin embargo, la patología miocárdica crónica fue similar, con la excepción de que 1/3 de las ratas adultas inoculadas presentaron fibrosis (AU)

Influencia de la edad de la rata en la evolución de la infección com trypanosoma cruzi / Influence of the age of the rat on the course of infection with trypanosoma cruzi

En la primera parte de este trabajo se estudió en la fase aguda, la parasitemia y respuesta inmune humoral específica, en ratas de línea "1", inoculadas al destete con 1x10**6 T. cruzi vivos de la cepa Tulahuén (GD), y adultos jóvenes con 1x10**6 T. cruzi (GA) y con 7x10**6 T. cruzi, cantidad equivalente a la inoculada en los destetes según peso (GA-1). La parasitemia fue significativamente mayor en el GD que en los GA y GA-1. Por otro lado, el GD presentó bajos títulos de anticuerpos, en relación a los adultos con ambas concentraciones de T. cruzi, que tuvieron un comportamiento similar. En el período crónico se evaluaron, a los 180 días post-infección, los ECG y la histolatología de corazón en animales al destete y adultos, con sólo 1x10**6 T. cruzi. La frecuencia cardíaca en los animales infectados fue mayor que la de los testigos. La proporción de lesión cardíaca (miocarditis, pericarditis y/o fibrosis) fue superior en el GD y en el GA, con respecto al GT, y el GA presentó un 35,6% de fibrosis, significativamente diferente de los otros grupos. La lesión fue sobre todo leve, ventricular y no se visualizaron parásitos in situ. En síntesis, en la rata, en la fase aguda de la infección, se encontraron diferencias marcadas en serología y parasitemia según la edad del huésped; sin embargo, la patología miocárdica crónica fue similar, con la excepción de que 1/3 de las ratas adultas inoculadas presentaron fibrosis

Efecto de extractos ricos en ARN inmune sobre algunos parámetros inmunopatológicos de ratas infectadas con Trypanosoma cruzi / Effect of extracts rich in immune RNA on some immunopathological parameters of rats infected with Trypanosoma cruzi

Se estudió el efecto de una inyección única de un extracto rico en ARN inmune (Ext-ARNi) (4 mg/100 g peso), en ratas inoculadas con T. cruzi viables, realizada 5 días antes que el desafío con los parásitos. Se midieron parasitemia en la fase aguda, nivel y cinética de anticuerpos en forma crónica; ECG y estudio histopatológico de corazón por microscopía óptica &P, a los 6 meses de evolución. No se visualizaron cambios en la parasitemia, el nivel de anticuerpos específicos mostró diferenciass puntuales y el ECG no se modificó con la presencia del Ext-ARNi. Sólo el porcentaje de lesión cardíaca (miocarditis, pericarditis y/o fibrosis) se redujo significativamente en las ratas que recibieron Ext-ARNi y T. cruzi (17,6%), en comparación con el grupo desafiado con T. cruzi (66,7%), y sin diferencias con los controles de Ext-ARNi (34,4%), y testigos (15,6%). Se postula que el extracto rico en ARN inmune podría modificar la "calidad" de los anticuerpos que se forman, los que protegerían al parásito haciéndolo menos inmunogénico provocando, consecuentemente, menos lesión cardíaca. No se descarta la participación de componentes celulares u otros efectos en la fisiopatología de este mecanismo