P2 Purinergic Signaling in the Distal Lung in Health and Disease.

The distal lung provides an intricate structure for gas exchange in mammalian lungs. Efficient gas exchange depends on the functional integrity of lung alveoli. The cells in the alveolar tissue serve various functions to maintain alveolar structure, integrity and homeostasis. Alveolar epithelial cells secrete pulmonary surfactant, regulate the alveolar surface liquid (ASL) volume and, together with resident and infiltrating immune cells, provide a powerful host-defense system against a multitude of particles, microbes and toxicants. It is well established that all of these cells express purinergic P2 receptors and that purinergic signaling plays important roles in maintaining alveolar homeostasis. Therefore, it is not surprising that purinergic signaling also contributes to development and progression of severe pathological conditions like pulmonary inflammation, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and pulmonary fibrosis. Within this review we focus on the role of P2 purinergic signaling in the distal lung in health and disease. We recapitulate the expression of P2 receptors within the cells in the alveoli, the possible sources of ATP (adenosine triphosphate) within alveoli and the contribution of purinergic signaling to regulation of surfactant secretion, ASL volume and composition, as well as immune homeostasis. Finally, we summarize current knowledge of the role for P2 signaling in infectious pneumonia, ALI/ARDS and idiopathic pulmonary fibrosis (IPF).

Supramolecular Toxin Complexes for Targeted Pharmacological Modulation of Polymorphonuclear Leukocyte Functions.

The targeted pharmacological modulation of polymorphonuclear leukocytes (PMNs) is of major medical interest. These innate immune cells play a central role in the defense against pathogenic microorganisms. However, their excessive chemotactic recruitment into tissues after traumatic injury is detrimental due to local and systemic inflammation. Rho-GTPases, being the master regulators of the actin cytoskeleton, regulate migration and chemotaxis of PMNs, are attractive pharmacological targets. Herein, supramolecular protein complexes are assembled in a "mix-and-match" approach containing the specific Rho-inhibiting clostridial C3 enzyme and three PMN-binding peptides using an avidin platform. Selective delivery of the C3 Rho-inhibitor with these complexes into the cytosol of human neutrophil-like NB-4 cells and primary human PMNs ex vivo is demonstrated, where they catalyze the adenosine diphosphate (ADP) ribosylation of Rho and induce a characteristic change in cell morphology. Notably, the complexes do not deliver C3 enzyme into human lung epithelial cells, A549 lung cancer cells, and immortalized human alveolar epithelial cells (hAELVi), demonstrating their cell type-selectivity. The supramolecular complexes represent attractive molecular tools to decipher the role of PMNs in infection and inflammation or for the development of novel therapeutic approaches for diseases that are associated with hyperactivity and reactivity of PMNs such as post-traumatic injury.

Contemporary options for restoration of anterior teeth with composite.

The present article gives an overview of modern adhesive restoration in the anterior area, in view of the fact that modern dental therapy should be as minimally invasive as possible. Illustrated with multiple cases, the article shows possible prospective fields of indication.

Influence of matrix systems on proximal contact tightness of 2- and 3-surface posterior composite restorations in vivo.

OBJECTIVES: To investigate the influence of cavity preparation (MO/DO/MOD) and type of matrix system on proximal contact tightness of direct posterior composite restorations. MATERIALS AND METHODS: 85 patients in need of a two- or three surface Class II direct composite restoration were randomly divided into two treatment groups. Group 1 was treated with a sectional matrix system combined with a separation ring (Palodent); Group 2 was treated with a circumferential matrix system in combination with a retainer (Tofflemire). Proximal contact tightness was recorded before treatment and directly after finishing the restoration. RESULTS: For the two-surface cavities use of the separation ring resulted in a statistically significantly tighter proximal contacts at both the mesial and distal site (MO: 2.51±0.81 N; DO: 2.82±1.14 N) compared to the use of the circumferential (MO: -1.08±1.04 N; DO: -0.22±0.87 N) (p=0.01). Regarding the three-surface (MOD) cavities no statistically significant differences were found between the mesial and distal site, nor was there an effect of the used matrix system. No statistically significant influence of cavity design (mesially/distally) was recorded for all cavities (MO, DO and MOD). CONCLUSIONS: Use of the sectional matrix system in two-surface Class II cavities resulted in statistically significantly tighter proximal contacts than the use of the circumferential matrix system. For the three-surface no statistically significant differences in contact tightness were found between the different matrix systems. Location of the cavity (mesially or distally) did not show to have any statistically significant effect on the obtained proximal contact tightness.