Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chagas' disease is caused by Trypanosoma cruzi, which is transmitted by reduviid bugs. The World Health Organization has estimated that about 16-18 million people in the Americas are infected, and that more than 100 million are at risk. In the present study we have used a murine model to analyse if particular T. cruzi strains (Tulahuen strain and SGO-Z12 isolate from a chronic patient) and/or re-infection may determine, during the indeterminate phase of experimental Chagas' disease, changes that could explain the different evolution of cardiac lesions. Re-infected mice reached higher parasitaemias than those infected for the first time. The survival in the indeterminate phase of mice infected with Tulahuen strain was 50.0%, while the SGO-Z12-infected group presented a significantly higher survival rate (77.1%; P <0.01). The SGO-Z12-re-infected group showed a survival rate (70.9%) significantly higher than that of the Tulahuen-re-infected group (37.0%; P <0.01). Electrocardiographic abnormalities were found in 66% of Tulahuen-infected mice, while in SGO-Z12-infected group such abnormalities were found in only 36% of animals ( P <0.01). The two groups exhibited similar percentages of electrocardiographic dysfunction on re-infection, although intraventricular blocks were more frequent in Tulahuen-re-infected mice ( P <0.01). Hearts from infected or re-infected mice with either parasite showed mononuclear infiltrates. The SGO-Z12-re-infected and Tulahuen-re-infected groups exhibited a significantly diminished affinity ( P <0.05) and a significantly increased density ( P <0.05) of cardiac beta-adrenergic receptors compared with the infected and non-infected groups. The indeterminate phase of Chagas' disease is defined as a prolonged period that is clinically silent, but the present findings show that different T. cruzi strains and re-infection are able to alter the host-parasite equilibrium, and these factors may be responsible for inducing progressive cardiopathy.
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PMID:Indeterminate Chagas' disease: Trypanosoma cruzi strain and re-infection are factors involved in the progression of cardiopathy. 1265 87

Trypanosoma cruzi trypanothione reductase is an enzyme that has been identified as a potential target for chemotherapy. Thioridazine inhibits it and prevented cardiopathy in mice infected with T. cruzi Tulahuen strain. As not all T. cruzi strains respond to treatment in the same way, an isolate from a chronic patient (SGO Z12) was used; parasitaemias were studied along with, survival, serology, electrocardiography, histology and cardiac beta receptor function. Parasitaemia in thioridazine (80 mg/(kg day) for 3 days) treated mice was less and lasted for a shorter period (P < 0.01), there were reduced electrocardiographic and histological alterations and significantly improved survival (80% of non-treated died). Treated mice had lower receptor affinity and higher density as a compensatory mechanism, modifying the course of T. cruzi infection (SGO Z12 isolate) and preventing the consequent cardiopathy.
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PMID:Thioridazine treatment prevents cardiopathy in Trypanosoma cruzi infected mice. 1519 37

The pathogenesis of chronic chagasic cardiopathy is still under discussion; there is considerable evidence that inflammatory infiltrates and their mediators have a direct effect on cardiac cells. Here we studied the structure and function of cardiac mitochondria in chronic chagasic myocardiopathy. Cardiac mitochondrial structure and enzyme activity of citrate synthase and complexes I to IV of the respiratory chain were studied in albino Swiss mice infected with Trypanosoma cruzi (Tulahuen strain or SGO Z12 isolate) on 365 days post-infection (dpi). The presence of parasites in cardiac and skeletal muscle was also investigated. The activity of complexes I to IV was altered in different ways, according to the strain employed (P<0.0001), in relation to the cristae disorganisation and the parasite persistence found in the Tulahuen group, and the chronic inflammatory process described in both groups; citrate synthase activity also increased in both infected groups. Changes in mitochondrial structure were detected in 89% of Tulahuen- and 58% of SGO Z12-infected mice. In this paper we demonstrate that parasite persistence and inflammation are likely to be involved in the structural and functional alterations in cardiac mitochondria from chronically T. cruzi-infected mice, demonstrating that the parasite strain determines different mitochondrial changes in chagasic cardiopathy.
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PMID:Mitochondrial involvement in chronic chagasic cardiomyopathy. 2147 Jun 46

Chagasic cardiopathy has become one of the most frequent causes of heart failure and sudden death, as well as one of the most common causes of cardio-embolic stroke in Latin America. The myocyte response to oxidative stress involves the progression of cellular changes, primarily targeting the mitochondria and modifying therefore the energy supply. In this paper we analysed the effect of the infection of mice with 2 different strains of Trypanosoma cruzi (Tulahuen and SGO Z12) in the chronic indeterminate stage (75 days post-infection), upon the structure and function of cardiac mitochondria. The structural results showed that 83% of the mitochondria from the Tulahuen-infected mice presented an increase in their matrix and 91% of the mitochondria from the SGO Z12-infected group showed a reduction in their diameter (P < 0.05). When the Krebs cycle and mitochondrial respiratory chain functionality was analysed through the measurement of the citrate synthase and complexes I to IV activity, it showed that their activity was altered in all cases in a similar manner in both infected groups. In this paper we have demonstrated that the chronic indeterminate phase is not 'silent' and that cardiac mitochondria are clearly involved in the genesis and progression to the chronic chagasic cardiopathy when different factors alter the host-parasite equilibrium.
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PMID:Chronic indeterminate phase of Chagas' disease: mitochondrial involvement in infection with two strains. 2313 84

Trypanosoma cruzi invasion and replication in cardiomyocytes and other tissues induce cellular injuries and cytotoxic reactions, with the production of inflammatory cytokines and nitric oxide, both sources of reactive oxygen species. The myocyte response to oxidative stress involves the progression of cellular changes primarily targeting mitochondria. Similar alterations could be taking place in mitochondria from the skeletal muscle; if that is the case, a simple skeletal muscle biopsy would give information about the cardiac energetic production that could be used as a predictor of the chagasic cardiopathy evolution. Therefore, in the present paper we studied skeletal muscle mitochondrial structure and the enzymatic activity of citrate synthase and respiratory chain complexes I to IV (CI-CIV), in Albino Swiss mice infected with T. cruzi, Tulahuen strain and SGO Z12 and Lucky isolates, along the infection. Changes in the mitochondrial structure were detected in 100% of the mitochondria analyzed from the infected groups: they all presented at least 1 significant abnormality such as increase in their matrix or disorganization of their cristae, which are probably related to the enzymatic dysfunction. When we studied the Krebs cycle functionality through the measurement of the specific citrate synthase activity, we found it to be significantly diminished during the acute phase of the infection in Tulahuen and SGO Z12 infected groups with respect to the control one; citrate synthase activity from the Lucky group was significantly increased (p<0.05). The activity of this enzyme was reduced in all the infected groups during the chronic asymptomatic phase (p<0.001) and return to normal values (Tulahuen and SGO Z12) or increased its activity (Lucky) by day 365 post-infection (p.i.). When the mitochondrial respiratory chain was analyzed from the acute to the chronic phase of the infection through the measurement of the activity of complexes I to IV, the activity of CI remained similar to control in Tulahuen and Lucky groups, but was significantly augmented in the SGO Z12 one in the acute and chronic phases (p<0.05). CII increased its activity in Tulahuen and Lucky groups by day 75 p.i. and in SGO Z12 by day 365 p.i. (p<0.05). CIII showed a similar behavior in the 3 infected groups, remaining similar to control values in the first two stages of the infection and significantly increasing later on (p<0.0001). CIV showed an increase in its activity in Lucky throughout all stages of infection (p<0.0001) and an increase in Tulahuen by day 365days p.i. (p<0.0001); SGO Z12 on the other hand, showed a decreased CIV activity at the same time. The structural changes in skeletal muscle mitochondria and their altered enzyme activity began in the acute phase of infection, probably modifying the ability of mitochondria to generate energy; these changes were not compensated in the rest of the phases of the infection. Chagas is a systemic disease, which produces not only heart damage but also permanent skeletal muscle alterations.
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PMID:Mitochondrial dysfunction in skeletal muscle during experimental Chagas disease. 2583 81