Annals of medicine
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Calcium sensitizers are a new group of inotropic drugs. Levosimendan is the only calcium sensitizer in clinical use in Europe. Its mechanism of action includes both calcium sensitization of contractile proteins and the opening of adenosine triphosphate (ATP)-dependent potassium channels as mechanism of vasodilation. ⋯ These trials did not require filling pressures to be measured. The two trials showed that levosimendan improves the symptoms of heart failure, but does not improve survival. The results raise the question whether a 24-hour levosimendan infusion can be used without invasive hemodynamic monitoring.
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Despite the fact that the heart requires huge amounts of energy to sustain contractile function, it has limited energy reserves and must therefore continually produce large amounts of adenosine triphosphate (ATP) to sustain function. Fatty acids are the primary energy substrate of the adult heart, with more than 60% of the energy normally obtained from the oxidation of fatty acids, the remainder coming from the metabolism of carbohydrates. Alterations in both the rates of ATP production and the type of energy substrate used by the heart can have consequences on contractile function, as well as on its ability to respond to energetic stresses. ⋯ Heart failure is characterized by an inefficient pumping of the heart, which fails to meet the energy requirements of the body. A number of cardiomyopathies can lead to heart failure. This paper will review the alterations in energy metabolism that occur in a number cardiomyopathies, including ischemic and diabetic cardiomyopathies, as well as hypertrophic cardiomyopathies resulting from mutations in enzymes involved in energy metabolism, such as 5' adenosine monophosphate-activated protein kinase (AMPK).
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Over the past few years the field of innate immunity has undergone a revolution with the discovery of pattern recognition molecules (PRM) and their role in microbe detection. Among these molecules, the Nod-like receptors (NLRs) have emerged as key microbial sensors that participate in the global immune responses to pathogens and contribute to the resolution of infections. ⋯ Furthermore, mutations in the genes that encode these proteins have been associated with complex inflammatory disorders including Crohn's disease, asthma, familial cold urticaria, Muckle-Wells syndrome, and Blau syndrome. In this review we will present the current knowledge on the role of these proteins in immunity and inflammatory diseases.
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Allogeneic bone marrow or blood stem cell transplantation (SCT) has changed its face in the last two decades. The introduction of nonmyeloablative conditioning regimens has reduced procedure toxicity and allowed the application of SCT in patients and conditions in which SCT was not offered in the past. In this review we will summarize the changes and accomplishments achieved in the past years in the field of stem cell transplantation for malignant disorders.
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Since selective cyclooxygenase-2 inhibitors (coxibs) entered the market, there has been concern about the cardiovascular safety of coxibs. In addition, recent data suggest that classical non-steroidal anti-inflammatory drugs (NSAIDs) have a similar cardiovascular risk. Importantly, all of the clinical trials with NSAIDs and coxibs so far were not purpose-designed to specifically and prospectively address cardiovascular safety and were clearly underpowered to detect any meaningful differences. In this current uncertainty about safety of NSAIDs and coxibs, the definitive answer as to the net effect of coxibs and NSAIDs on cardiovascular events can only be provided by well designed adequately powered, long-term clinical trials, which is now under way.