Metabolomics is the study of small, organic molecules within biochemical pathways. With advancement of technology, nuclear magnetic resonance, gas chromatography, and mass spectrometry have allowed for the discovery and analysis of large databases of metabolites implicated in heart failure. Metabolomics also explores the patient and environment interactions and unlocks the link between environmental exposures and the development of cardiovascular disease. Although a relatively new field, metabolomics is poised to become a clinically impactful field that develops novel biomarkers and explores new therapeutic interventions in heart failure.
Digoxin remains one of the oldest therapies for heart failure; however, its safety and efficacy have been controversial since its initial use. Questions that remain include the clinical efficacy of digoxin when added to contemporary medical therapy, when and if it should be added, and how to minimize adverse effects. In this review, we will summarize recent data on the use of digoxin in systolic heart failure and address some of the controversies regarding the role of digoxin in the modern era of heart failure treatment.
The advantages gained by a combined treatment of different chemical protectors on short-term lethality of X-irradiated adult male mice have been studied. The following compounds were given alone or in a mixture of two or three compounds: 16,16-dimethyl PGE2 (PGE2), cysteine (Cys), glucan, glutathione (GSH), 5-hydroxytryptamine (5-HT), mercaptoproprionylglycine (MPG), or WR-2721. The survival of mice treated before X irradiation with the optimal dose of each radioprotector given separately shows that WR-2721 and 5-HT yield the best protection with dose reduction factors (DRFs) of 2.2 and 1.7, respectively. Cysteine, glucan, PGE2, MPG, and GSH, with DRFs of 1.4, 1.4, 1.2, 1.1, and 1.1, respectively, are less efficient radioprotectors. When PGE2 was combined with a low dose of WR-2721 (200 mg/kg), the protection increased in a synergistic way. The increase in protection offered by a combination of PGE2 with Cys, glucan, GSH, or 5-HT is less marked and the effect obtained is only additive. A synergistic action is also obtained with a combination of WR-2721 (200 mg/kg) and 5-HT (8 mg/kg) (DRF 2.7).
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