N-Octanoyl-Dopamine inhibits cytokine production in activated T-cells and diminishes MHC-class-II expression as well as adhesion molecules in IFN gamma-stimulated endothelial cells

IFN gamma enhances allograft immunogenicity and facilitates T-cell mediated rejection. This may cause interstitial fibrosis and tubular atrophy (IFTA), contributing to chronic allograft loss. We assessed if inhibition of T-cell activation by N-octanoyl dopamine (NOD) impairs adherence of activated T-cells to endothelial cells and the ability of activated T-cells to produce IFN gamma. We also assessed if NOD affects IFN gamma mediated gene expression in endothelial cells. The presence of NOD during T-cell activation significantly blunted their adhesion to unstimulated and cytokine stimulated HUVEC. Supernatants of these T-cells displayed significantly lower concentrations of TNF alpha and IFN gamma and were less capable to facilitate T-cell adhesion. In the presence of NOD VLA-4 (CD49d/CD29) and LFA-1 (CD11a/CD18) expression on T-cells was reduced. NOD treatment of IFN gamma stimulated HUVEC reduced the expression of MHC class II transactivator (CIITA), of MHC class II and its associated invariant chain CD74. Since IFTA is associated with T-cell mediated rejection and IFN gamma to a large extent regulates immunogenicity of allografts, our current data suggest a potential clinical use of NOD in the treatment of transplant recipients. Further in vivo studies are warranted to confirm these in vitro findings and to assess the benefit of NOD on IFTA in clinically relevant models

R&D investment and financing constraints of small and medium-sized firms

Capital investment, Censored regression models, Financial constraints, Panel data, R&D investment, L26, O31, O32,

Type of Exercise Training and Training Methods

There is general agreement that exercise train-ing leads to functional, morphological, and metabolic adaptations of different biological systems, thereby increasing overall physical performance and promoting good health. Thus, an active lifestyle is propagated in all age groups. However, not every exercise routine or workout is suitable for everyone. Inappropriate training can also pose risks, and too low or too high training intensity or volume often does not lead to the expected success. To ensure signifi-cant benefits, specific principles and strategies need to be considered and accustomed to the individual.This chapter summarizes the key exercise variables and training principles to consider when developing a training program to improve or maintain performance and health. In addi-tion, the various steps for creating an individ-ual training program are described, and an overview of the different training methods and training strategies is given