13 research outputs found
The Effects of Mn2+ on the Proliferation, Osteogenic Differentiation and Adipogenic Differentiation of Primary Mouse Bone Marrow Stromal Cells
Reversing arterial stiffening and calcification: A pipe dream?
The development of technical means to non-invasively investigate the cardiovascular system on other features than pulse and blood pressure, slowly led to the recognition that additional characteristics of the heart and vasculature play a crucial role in the pathogenesis of cardiovascular disease. Possibly the most prominent feature is arterial stiffness. Although being an inevitable consequence of aging and inseparable phenomenon with hypertension, it is clear that it predicts cardiovascular risk independently form these two factors. The variability of arterial stiffness is explained by a large range of endocrine, metabolic, haemodynamic, structural and functional properties, that all frequently occur together in chronic kidney disease. Although calcification of the tunica media in the arterial wall, a hallmark of chronic kidney disease, appears difficult to improve, several other components that contribute to arterial stiffness are likely more accessible for modification. Although it is not proven that specifically targeting arterial stiffness translates into improved clinical outcome, this pathological feature of the arterial system is likely neglected clinically and has a sound basis for rational intervention, preferably preceded by interventional trials with clinically important endpoints. In this chapter modifiable and hardly-modifiable factors that likely contribute to arterial stiffness in the setting of chronic kidney disease are addressed. Although areas of uncertainty exist and are underlined, raising awareness of the relevance of this neglected feature of the cardiovascular system, holds the promise of improving the unacceptably high prevalence of complications in chronic kidney disease
Back to the future: oral targeted therapy for RA and other autoimmune diseases
The molecular biology revolution coupled with the development of monoclonal antibody technology enabled remarkable progress in rheumatology therapy, comprising an array of highly effective biologic agents. With advances in understanding of the molecular nature of immune cell receptors came elucidation of intracellular signalling pathways downstream of these receptors. These discoveries raise the question of whether selective targeting of key intracellular factors with small molecules would add to the rheumatologic armamentarium. In this Review, we discuss several examples of this therapeutic strategy that seem to be successful, and consider their implications for the future of immune-targeted treatments. We focus on kinase inhibitors, primarily those targeting Janus kinase family members and spleen tyrosine kinase, given their advanced status in clinical development and application. We also summarize other targets involved in signalling pathways that might offer promise for therapeutic intervention in the future