The priming effect of extracellular UTP on human neutrophils: Role of calcium released from thapsigargin-sensitive intracellular stores

P2Y2 receptors, which are equally responsive to ATP and UTP, can trigger intracellular signaling events, such as intracellular calcium mobilization and mitogen-activated protein (MAP) kinase phosphorylation in polymorphonuclear leukocytes (PMN). Moreover, extracellular nucleotides have been shown to prime chemoattractant-induced superoxide production. The aim of our study was to investigate the mechanism responsible for the priming effect of extracellular nucleotides on reactive oxygen species (ROS) production induced in human neutrophils by two different chemoattractants: formyl-methionyl-leucyl-phenylalanine (fMLP) and interleukin-8 (IL-8). Nucleotide-induced priming of ROS production was concentration- and time-dependent. When UTP was added to neutrophil suspensions prior to chemoattractant, the increase of the response reached the maximum at 1 min of pre-incubation with the nucleotide. UTP potentiated the phosphorylation of p44/42 and p38 MAP kinases induced by chemoattractants, however the P2 receptor-mediated potentiation of ROS production was still detectable in the presence of a SB203580 or U0126, supporting the view that MAP kinases do not play a major role in regulating the nucleotide-induced effect. In the presence of thapsigargin, an inhibitor of the ubiquitous sarco-endoplasmic reticulum Ca2+-ATPases in mammalian cells, the effect of fMLP was not affected, but UTP-induced priming was abolished, suggesting that the release of calcium from thapsigargin-sensitive intracellular stores is essential for nucleotide-induced priming in human neutrophils

Current concepts in locking plate fixation of proximal humerus fractures

Despite numerous available treatment strategies, the management of complex proximal humeral fractures remains demanding. Impaired bone quality and considerable comorbidities pose special challenges in the growing aging population. Complications after operative treatment are frequent, in particular loss of reduction with varus malalignment and subsequent screw cutout. Locking plate fixation has become a standard in stabilizing these fractures, but surgical revision rates of up to 25% stagnate at high levels. Therefore, it seems of utmost importance to select the right treatment for the right patient. This article provides an overview of available classification systems, indications for operative treatment, important pathoanatomic principles, and latest surgical strategies in locking plate fixation. The importance of correct reduction of the medial cortices, the use of calcar screws, augmentation with bone cement, double-plate fixation, and auxiliary intramedullary bone graft stabilization are discussed in detail