Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chagas' disease, caused by Trypanosoma cruzi infection, is one of the main causes of death due to heart failure in Latin American countries. Benznidazole, the chemotherapeutic agent most often used for the treatment of chagasic patients, is highly toxic and has limited efficacy, especially in the chronic phase of the disease. In the present study we used a mouse model of chronic Chagas' disease to investigate the effects of benznidazole treatment during the chronic phase on disease progression. The hearts of benznidazole-treated mice had decreased parasitism and myocarditis compared to the hearts of untreated chagasic mice. Both groups of Trypanosoma cruzi-infected mice had significant alterations in their electrocardiograms compared to those of the healthy mice. However, untreated mice had significantly higher cardiac conduction disturbances than benznidazole-treated mice, including intraventricular conduction disturbances, atrioventricular blocks, and extrasystoles. The levels of antibodies against T. cruzi antigens (epimastigote extract, P2beta, and trans-sialidase) as well as antibodies against peptides of the second extracellular loops of beta1-adrenergic and M2-muscarinic cardiac receptors were also lower in the sera from benznidazole-treated mice than in the sera from untreated mice. These results demonstrate that treatment with benznidazole in the chronic phase of infection prevents the development of severe chronic cardiomyopathy, despite the lack of complete parasite eradication. In addition, our data highlight the role of parasite persistence in the development of chronic Chagas' disease and reinforce the importance of T. cruzi elimination in order to decrease or prevent the development of severe chagasic cardiomyopathy.
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PMID:Treatment with benznidazole during the chronic phase of experimental Chagas' disease decreases cardiac alterations. 1579 34

American trypanosomiasis is a parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. Chagas disease is endemic in Latin America, where an estimated 10-14 million people are infected, and an emerging disease in Europe and the USA. Trypanosoma cruzi is transmitted by blood-sucking bugs of the family Reduviidae. Rhodnius prolixus, Panstrongylus megistus, Triatoma infestans, and T. dimidiata are the main vectors in the sylvatic cycle. Non vector-borne transmission includes blood transfusion, congenital and oral transmission, transplantation, and accidental infections. Most cases of acute infection occur in childhood and are usually asymptomatic, although severe myocarditis and meningoencephalitis may occur. Approximately 30% of T. cruzi-infected people will develop the chronic stage of the disease. Chronic chagasic cardiomyopathy is characterized by progressive heart failure, arrhythmias, intraventricular conduction defects, sudden death, and peripheral thromboembolism. Acute exacerbation can occur in individuals with involvement of cellular immunity such as advanced AIDS (acquired immunodeficiency syndrome), and transplant-associated immunosuppression. Neurological involvement may present with encephalitis, meningoencephalitis, or a space-occupying cerebral lesion called chagoma. Chagas disease is a major cause of ischemic stroke in Latin America. Several epidemiological studies have found an association between T. cruzi infection and cardioembolic ischemic stroke. Benznidazole and nifurtimox are the two available trypanocide drugs against T. cruzi.
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PMID:American trypanosomiasis. 2382 3

Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (Nfx) are recognized as effective drugs for the treatment of Chagas disease by the World Health Organization, but both have high toxicity and limited efficacy, especially in the chronic disease phase. At low doses, aspirin (ASA) has been reported to protect against T. cruzi infection. We evaluated the effectiveness of BZ in combination with ASA at low doses during the acute disease phase and evaluated cardiovascular aspects and cardiac lesions in the chronic phase. ASA treatment prevented the cardiovascular dysfunction (hypertension and tachycardia) and typical cardiac lesions. Moreover, BZ+ASA-treated mice had a smaller cardiac fibrotic area than BZ-treated mice. These results were associated with an increase in numbers of eosinophils and reticulocytes and levels of nitric oxide in the plasma and cardiac tissue of ASA-treated mice relative to respective controls. These effects of ASA and BZ+ASA in chronically infected mice were inhibited by pretreatment with the lipoxin A4 (LXA4) receptor antagonist Boc-2, indicating that the protective effects of ASA are mediated by ASA-triggered lipoxin. These results emphasize the importance of exploring new drug combinations for treatments of the acute phase of Chagas disease that are beneficial for patients with chronic disease.
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PMID:Combination Therapy Using Benznidazole and Aspirin during the Acute Phase of Experimental Chagas Disease Prevents Cardiovascular Dysfunction and Decreases Typical Cardiac Lesions in the Chronic Phase. 3236 19