Protein kinase C and acute respiratory distress syndrome.

The acute respiratory distress syndrome (ARDS) is a major public health problem and a leading source of morbidity in intensive care units. Lung tissue in patients with ARDS is characterized by inflammation, with exuberant neutrophil infiltration, activation, and degranulation that is thought to initiate tissue injury through the release of proteases and oxygen radicals. Treatment of ARDS is supportive primarily because the underlying pathophysiology is poorly understood. This gap in knowledge must be addressed to identify urgently needed therapies. Recent research efforts in anti-inflammatory drug development have focused on identifying common control points in multiple signaling pathways. The protein kinase C (PKC) serine-threonine kinases are master regulators of proinflammatory signaling hubs, making them attractive therapeutic targets. Pharmacological inhibition of broad-spectrum PKC activity and, more importantly, of specific PKC isoforms (as well as deletion of PKCs in mice) exerts protective effects in various experimental models of lung injury. Furthermore, PKC isoforms have been implicated in inflammatory processes that may be involved in the pathophysiologic changes that result in ARDS, including activation of innate immune and endothelial cells, neutrophil trafficking to the lung, regulation of alveolar epithelial barrier functions, and control of neutrophil proinflammatory and prosurvival signaling. This review focuses on the mechanistic involvement of PKC isoforms in the pathogenesis of ARDS and highlights the potential of developing new therapeutic paradigms based on the selective inhibition (or activation) of specific PKC isoforms.

Current evidence from phase III clinical trials of selenium supplementation in critically Ill patients: why should we bother?

The importance of the trace element selenium for human health is well established. Selenium plays a central role in the formation of selenocysteine, a modified amino acid located in the catalytic center of selenoenzymes. The crucial role of selenium in these enzymes revolves around the maintenance of many redox systems in cellular and extracellular compartments. In addition, selenium plays an important role in thyroid hormone metabolism. Several clinical trials of selenium supplementation in critically ill patients have been conducted to date, providing an interesting and provoking mix of findings. Despite some promising results, no definitive answers regarding the effects of selenium supplementation on critically ill patient mortality or morbidity exist. Further research in the setting of well-designed, prospective, randomized trials is necessary to better define the role of selenium supplementation in critically ill patients.