"Challenges and facilitators-navigating in the landscape of spinal cord injury neuropathic pain"-a qualitative study on the use of prescribed drugs.

STUDY DESIGN: A qualitative study with an emergent design using semi-structured interviews in focus groups. OBJECTIVES: To explore the expectations, experiences and desires among individuals who are prescribed drugs for spinal cord injury (SCI) neuropathic pain (NP). SETTING: SCI rehabilitation centre. METHODS: Eighteen informants with SCI and NP were enrolled. The informants originated from large and small cities in southern Sweden. Data were collected in focus groups consisting of 4-5 individuals in four separate sessions. An emergent design was employed using an interview guide containing open questions. The interviews were transcribed verbatim and data were analyzed according to qualitative content analysis. RESULTS: A model of three themes emerged: "Balancing between pain and side-effects" described the difficult choices the informants had to make between drugs and their unwanted side-effects and pain, "Desiring competence and structure in pain management" described the informants wishes regarding pain management and "From hope to personal solutions" described the process from hope of total pain relief from drugs to the development of personal strategies. CONCLUSIONS: There is a great need for improvement of SCI-related neuropathic pain management since recommended drugs are insufficiently effective and accompanied by severe side-effects that impact quality of life but also due to structural limitations and physicians' lack of competence in pain management.

Solution-processed, highly-oriented supramolecular architectures of functionalized porphyrins with extended electronic states.

Thin films of aligned supramolecular architectures built from newly synthesized thiophene-substituted porphyrins have been processed from solution on surfaces.

New aminoimidazoles as ß-secretase (BACE-1) inhibitors showing amyloid-ß (Aß) lowering in brain.

Amino-2H-imidazoles are described as a new class of BACE-1 inhibitors for the treatment of Alzheimer's disease. Synthetic methods, crystal structures, and structure-activity relationships for target activity, permeability, and hERG activity are reported and discussed. Compound (S)-1m was one of the most promising compounds in this report, with high potency in the cellular assay and a good overall profile. When guinea pigs were treated with compound (S)-1m, a concentration and time dependent decrease in Aß40 and Aß42 levels in plasma, brain, and CSF was observed. The maximum reduction of brain Aß was 40-50%, 1.5 h after oral dosing (100 µmol/kg). The results presented highlight the potential of this new class of BACE-1 inhibitors with good target potency and with low effect on hERG, in combination with a fair CNS exposure in vivo.

Design and synthesis of ß-site amyloid precursor protein cleaving enzyme (BACE1) inhibitors with in vivo brain reduction of ß-amyloid peptides.

The evaluation of a series of aminoisoindoles as ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors and the discovery of a clinical candidate drug for Alzheimer's disease, (S)-32 (AZD3839), are described. The improvement in permeability properties by the introduction of fluorine adjacent to the amidine moiety, resulting in in vivo brain reduction of Aß40, is discussed. Due to the basic nature of these compounds, they displayed affinity for the human ether-a-go-go related gene (hERG) ion channel. Different ways to reduce hERG inhibition and increase hERG margins for this series are described, culminating in (S)-16 and (R)-41 showing large in vitro margins with BACE1 cell IC(50) values of 8.6 and 0.16 nM, respectively, and hERG IC(50) values of 16 and 2.8 µM, respectively. Several compounds were advanced into pharmacodynamic studies and demonstrated significant reduction of ß-amyloid peptides in mouse brain following oral dosing.

Polymer-assisted laser desorption/ionization analysis of small molecular weight compounds.

The use of non-polar, small polymers as matrices for the analysis of low molecular weight compounds in polymer-assisted laser desorption/ionization mass spectrometry (PALDI-MS) is demonstrated. The matrices evaluated were either based on an oligothiophene or a benzodioxin backbone. Metallocenes, polycyclic hydrocarbons, a fluorosurfactant, and a subset of small organic compounds with various functionalities, served as model analytes. The mechanism of ionization charge transfer is discussed and ionization potentials for the matrices in the study have been estimated using density functional theory (DFT) calculations. Some of the results are possibly contradictory to the generally accepted limiting conditions for gas-phase charge-transfer reactions. These results are interpreted in the light of energy pooling. Also a new mass calibration procedure for the low-mass region in positive ion mode is presented, and some aspects of the ionization/desorption process leading to radical cations are studied.