Pro-arrhythmogenic effects of Trypanosoma cruzi conditioned medium proteins in a model of bovine chromaffin cells.

Asymptomatic sudden death is the principal cause of mortality in Chagas disease. There is little information about molecular mechanisms involved in the pathophysiology of malignant arrhythmias in Chagasic patients. Previous studies have involved Trypanosoma cruzi secretion proteins in the genesis of arrhythmias ex vivo, but the molecular mechanisms involved are still unresolved. Thus, the aim was to determine the effect of these secreted proteins on the cellular excitability throughout to test its effects on catecholamine secretion, sodium-, calcium-, and potassium-conductance and action potential (AP) firing. Conditioned medium was obtained from the co-culture of T. cruzi and Vero cells (African green monkey kidney cells) and ultra-filtered for concentrating immunogenic high molecular weight parasite proteins. Chromaffin cells were assessed with the parasite and Vero cells control medium. Parasite-secreted proteins induce catecholamine secretion in a dose-dependent manner. Additionally, T. cruzi conditioned medium induced depression of both calcium conductance and calcium and voltage-dependent potassium current. Interestingly, this fact was related to the abolishment of the hyperpolarization phase of the AP produced by the parasite medium. Taken together, these results suggest that T. cruzi proteins may be involved in the genesis of pro-arrhythmic conditions that could influence the appearance of malignant arrhythmias in Chagasic patients.

Role of TNF in sickness behavior and allodynia during the acute phase of Chagas' disease.

Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, is associated with inflammation, discomfort and pain during the acute phase. The influence of TNF-α (tumor necrosis factor) in this disease outcome is controversial. In this way, the aim of this work was to determine the role of the TNF-α blocker etanercept in the pain, discomfort, and survival during the Chagas' acute phase of mice experimentally infected with a wild virulent strain of T. cruzi. The infection with this wild strain was responsible for a severe visceral inflammation and said parasite showed a tropism in peritoneal fluid cells. Etanercept was able to restore spontaneous vertical and horizontal activities during the second week after infection and to abolish mechanical allodynia during the first week after infection. Finally, etanercept delayed the mortality without any effect on the parasitemia rates. This is the first report that correlates sickness behavior and allodynia with TNF-α and suggests that this cytokine may play an important role in the physiopathology of the acute phase.

Induction of chagasic-like arrhythmias in the isolated beating hearts of healthy rats perfused with Trypanosoma cruzi-conditioned medium.

Chagas' myocardiopathy, caused by the intracellular protozoan Trypanosoma cruzi, is characterized by microvascular alterations, heart failure and arrhythmias. Ischemia and arrythmogenesis have been attributed to proteins shed by the parasite, although this has not been fully demonstrated. The aim of the present investigation was to study the effect of substances shed by T. cruzi on ischemia/reperfusion-induced arrhythmias. We performed a triple ischemia-reperfusion (I/R) protocol whereby the isolated beating rat hearts were perfused with either Vero-control or Vero T. cruzi-infected conditioned medium during the different stages of ischemia and subsequently reperfused with Tyrode's solution. ECG and heart rate were recorded during the entire experiment. We observed that triple I/R-induced bradycardia was associated with the generation of auricular-ventricular blockade during ischemia and non-sustained nodal and ventricular tachycardia during reperfusion. Interestingly, perfusion with Vero-infected medium produced a delay in the reperfusion-induced recovery of heart rate, increased the frequency of tachycardic events and induced ventricular fibrillation. These results suggest that the presence of parasite-shed substances in conditioned media enhances the arrhythmogenic effects that occur during the I/R protocol.

Induction of chagasic-like arrhythmias in the isolated beating hearts of healthy rats perfused with Trypanosoma cruzi-conditioned medium

Chagas' myocardiopathy, caused by the intracellular protozoan Trypanosoma cruzi, is characterized by microvascular alterations, heart failure and arrhythmias. Ischemia and arrythmogenesis have been attributed to proteins shed by the parasite, although this has not been fully demonstrated. The aim of the present investigation was to study the effect of substances shed by T. cruzi on ischemia/reperfusion-induced arrhythmias. We performed a triple ischemia-reperfusion (I/R) protocol whereby the isolated beating rat hearts were perfused with either Vero-control or Vero T. cruzi-infected conditioned medium during the different stages of ischemia and subsequently reperfused with Tyrode's solution. ECG and heart rate were recorded during the entire experiment. We observed that triple I/R-induced bradycardia was associated with the generation of auricular-ventricular blockade during ischemia and non-sustained nodal and ventricular tachycardia during reperfusion. Interestingly, perfusion with Vero-infected medium produced a delay in the reperfusion-induced recovery of heart rate, increased the frequency of tachycardic events and induced ventricular fibrillation. These results suggest that the presence of parasite-shed substances in conditioned media enhances the arrhythmogenic effects that occur during the I/R protocol.

Prevalence and risk factors for gallstone disease.

Gallstone disease is a main public health problem. The overall prevalence data range from 3.9% in the pre-echographic era to 13.7% when ultrasonography was used as a diagnostic tool. This study is aimed to determine the prevalence of gallstone disease in a medium income level population in Lima, as well as the relationship with some risk factors: age, sex, familiar history and obesity. A total of 534 adult men and women from a medium economic level underwent ultrasonographic examination of abdomen for detection of gallstone disease (July 2003). The echographic evaluation was performed by 10 general surgeons trained in ultrasonography. Likewise, 4 risk factors--age, gender, familial history, and obesity--were analyzed. Pearson chi2 test (2-sided) was used with a probability of <0.05 for statistical significance and logistic regression analyses for assessment of confounding factors. The prevalence founded was 15%. Eighty-one of 534 participants had lithiasis. Compared to the age group under 30, the odds ratio for the 31 to 50 years and >50 years of age group was 0.9 and 1.1, respectively. The female-male ratio was 1.07 and the odds ratio 0.8. The prevalence of gallstone disease in people reporting a first-degree relative with lithiasis was 21%, whereas in participants without such a condition, it was 13%. On the other hand, a familial history was present in 38% of the lithiasis group and in 25% of the nonlithiasis group. The odds ratio for familial history was 1.8 (P = 0.01, 95% confidence interval 1.1-2.9). The prevalence of the disease for body mass index <24, 25 to 29, and higher than 30 was 17%, 14% and 13%, respectively. Compared to the reference group (body mass index <24), the other 2 groups (body mass index 25-29 and >30) both had a similar odds ratio, 0.8. Logistic regression analyses showed an odds ratio of 1.9 for familiar history (95% confidence interval 1.1-3.2), whereas the odds ratio of the overweight (body mass index 25-29) and obese group (body mass index >30) when compared to the normal group, BMI <24, was 0.7 and 0.9, respectively. The prevalence data for gallstone disease remain slightly higher than those previously reported. Although the familiar history was the only characteristic with a statistically significant positive relationship with lithiasis, additional studies are needed because few biases could not be completely avoided and some confounding factors were not controlled.