Cervical motion preservation prostheses are considered a developing technology, with widespread clinical use beginning in the early 2000s. They are developed to reduce adjacent segment degeneration... Show moreCervical motion preservation prostheses are considered a developing technology, with widespread clinical use beginning in the early 2000s. They are developed to reduce adjacent segment degeneration (ASD) in the postsurgical follow-up by maintaining range of motion (ROM). However, it is still a controversial issue. The main objective of this thesis was to uncover the relationship between preserved motion and radiological ASD in patients with single-level cervical radiculopathy. Other factors which may be correlated to ASD were studied as well. Show less
Most small-molecule drugs are designed to interact with their biological targets under equilibrium binding conditions, whereby the desired drug-protein interaction is a rapid and reversible (non... Show moreMost small-molecule drugs are designed to interact with their biological targets under equilibrium binding conditions, whereby the desired drug-protein interaction is a rapid and reversible (non-covalent) process. As an extension to maximizing the strength of these noncovalent molecular interactions, a less conventional strategy termed ‘covalent interactions’ has recently gained reputation in the field of drug discovery. In this thesis a covalent strategy is applied and shown to be compatible with a target-directed, structure-guided discovery paradigm, with a focus on adenosine receptors as drug targets. The development and application of chemical tools and strategies are described to study three subtypes of ARs, A1R, A2AR and A3R. We set up a work flow of in vitro pharmacological assays as a robust tool for measuring and quantifying covalent modulation. Besides, we developed affinity-based probes, which allow monitoring of GPCR expression in cell fragments. Combined, this research approach may ultimately aid in the discovery and development of novel adenosine receptor-based therapeutics that lack potential side effects as much as possible. Show less
