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)

Doxorubicin is an effective chemotherapeutic agent against a broad range of tumors. However, a threshold dose of doxorubicin causes an unacceptably high incidence of heart failure and limits its clinical utility. We have established two models of doxorubicin cardiotoxicity in mice: 1) in an acute model, mice are treated with 15 mg/kg of doxorubicin once; and 2) in a chronic model, they receive 3 mg/kg weekly for 12 wk. Using echocardiography, we have monitored left ventricular function during treatment in the chronic model and seen the expected development of dilated cardiomyopathy. Treated mice showed histological abnormalities similar to those seen in patients with doxorubicin cardiomyopathy. To investigate transcriptional regulation in these models, we used a muscle-specific cDNA microarray. We have identified genes that respond to doxorubicin exposure in both models and confirmed these results using real-time PCR. In the acute model, a set of genes is regulated early and rapidly returns to baseline levels, consistent with the half-life of doxorubicin. In the chronic model, which mimics the clinical situation much more closely, we identified dysregulated genes that implicate specific mechanisms of cardiac toxicity. These include STARS, a hypertrophy-responsive gene; SNF1-kinase, a potential modulator of ATP levels; and AXUD1, a downstream target of the proapoptotic regulator AXIN1.
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PMID:Transcriptional analysis of doxorubicin-induced cardiotoxicity. 1624 10

Natriuretic peptides, especially BNP and NT-proBNP became useful tool for both, the diagnostics and the estimation of prognosis in chronic heart failure. As the plasma levels of natriuretic peptides copy changes in clinical status, an attractive hypothesis was formed saying that BNP/NT-proBNP guided therapy could have better clinical outcomes than therapy guided by patients' clinical status (symptoms). In past few years this hypothesis was tested in several randomized controlled clinical trials (STARS-BNP, TIME-CHF, PRIMA). However, results of these trials are very controversial. There are preliminary results of clinical trial OPTIMA referred in this paper, too. This one-centre study was performed at the authors' institution. Altogether 52 patients with chronic heart failure were randomized to one of the above mentioned treatment strategies. The rate of cardiovascular events was lower in the patients in whom the treatment was guided by BNP values compared to the patients in whom the treatment was guided by their clinical status. However, the difference was not statistically significant.
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PMID:[Will the therapy of chronic heart failure be guided by plasma levels of natriuretic peptides?]. 1989 25