Non-invasive assessment of microvascular dysfunction in patients with microvascular angina.

Background: We aimed to evaluate the microvascular function in patients with microvascular angina (MVA) by assessing 1) the endothelial glycocalyx barrier properties using sublingual microscopy, and 2) the myocardial perfusion reserve using cardiovascular magnetic resonance (CMR) imaging.

Methods: Sublingual microscopy was performed in 13 MVA patients (angina pectoris, ST-depression on treadmill testing, normal coronary angiogram) and compared with 2 control groups of 13 volunteers and 14 patients with known obstructive coronary artery disease (CAD). To test the glycocalyx-mediated microvascular responsiveness, the erythrocyte perfused boundary region (PBR) was assessed at baseline and after nitroglycerin challenge.

Efficacy of radiation safety glasses in interventional radiology.

Purpose: This study was designed to evaluate the reduction of the eye lens dose when wearing protective eyewear in interventional radiology and to identify conditions that optimize the efficacy of radiation safety glasses.

Methods: The dose reduction provided by different models of radiation safety glasses was measured on an anthropomorphic phantom head. The influence of the orientation of the phantom head on the dose reduction was studied in detail.

Brain imaging in chronic epilepsy patients after depth electrode (stereoelectroencephalography) implantation: magnetic resonance imaging or computed tomography?

Background: The accurate localization of depth electrodes in epilepsy surgery is important for correct interpretation of stereoelectroencephalography recordings and neurosurgical resection. Unfortunately, image quality in postimplantation magnetic resonance imaging (MRI) is degraded by metal artifacts. The registration of postimplantation computed tomography (CT) or MRI to preimplantation (artifact-free) MRI facilitates electrode imaging and optimal visualization of brain anatomy.

Imaging cold-activated brown adipose tissue using dynamic T2*-weighted magnetic resonance imaging and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography.

Objectives: The objective of this study was to explore the use of magnetic resonance imaging (MRI) to identify and quantify active brown adipose tissue (BAT) in adult humans. 2-Deoxy-2-[F]fluoro-D-glucose (FDG) positron emission tomography (PET) combined with computed tomography was used as a reference method to identify active BAT depots and to guide the MRI data analysis.

Materials And Methods: The ethics committee of the institute approved the protocol, and all participants provided written informed consent before participation.

Extracting atomic numbers and electron densities from a dual source dual energy CT scanner: experiments and a simulation model.

Background And Purpose: Dual energy CT (DECT) imaging can provide both the electron density ρ(e) and effective atomic number Z(eff), thus facilitating tissue type identification. This paper investigates the accuracy of a dual source DECT scanner by means of measurements and simulations. Previous simulation work suggested improved Monte Carlo dose calculation accuracy when compared to single energy CT for low energy photon brachytherapy, but lacked validation.

Membrane Permeabilization by Oligomeric α-Synuclein: In Search of the Mechanism.

Background: The question of how the aggregation of the neuronal protein α-synuclein contributes to neuronal toxicity in Parkinson's disease has been the subject of intensive research over the past decade. Recently, attention has shifted from the amyloid fibrils to soluble oligomeric intermediates in the α-synuclein aggregation process. These oligomers are hypothesized to be cytotoxic and to permeabilize cellular membranes, possibly by forming pore-like complexes in the bilayer.

Membrane interactions of oligomeric alpha-synuclein: potential role in Parkinson's disease.

alpha-Synuclein is a small neuronal protein that has been implicated to play an important role in Parkinson's disease. Genetic mutations and multiplications in the alpha-synuclein gene can cause familial forms of the disease. In aggregated fibrillar form, alpha-synuclein is the main component of Lewy bodies, the intraneuronal inclusion bodies characteristic of Parkinson's disease.

A stable lipid-induced aggregate of alpha-synuclein.

The Parkinson's disease-related protein alpha-Synuclein (alphaS) is a 140 residue intrinsically disordered protein. Its membrane-binding properties are thought to be relevant for its physiological or pathologic activity. Here, the interaction of alphaS with POPG [1-Palmitoyl-2-Oleoyl-sn-Glycero-3-(Phosphorac-(1-glycerol))] small unilamellar vesicles (SUVs) is investigated by spin-label EPR using double electron-electron resonance (DEER).

Lipid bilayer disruption by oligomeric alpha-synuclein depends on bilayer charge and accessibility of the hydrophobic core.

Soluble oligomeric aggregates of alpha-synuclein have been implicated to play a central role in the pathogenesis of Parkinson's disease. Disruption and permeabilization of lipid bilayers by alpha-synuclein oligomers is postulated as a toxic mechanism, but the molecular details controlling the oligomer-membrane interaction are still unknown. Here we show that membrane disruption strongly depends on the accessibility of the hydrophobic membrane core and that charge interactions play an important but complex role.

Membrane binding of oligomeric alpha-synuclein depends on bilayer charge and packing.

Membrane disruption by oligomeric alpha-synuclein (alphaS) is considered a likely mechanism of cytotoxicity in Parkinson's disease (PD). However, the mechanism of oligomer binding and the relation between binding and membrane disruption is not known. We have visualized alphaS oligomer-lipid binding by fluorescence microscopy and have measured membrane disruption using a dye release assay.

Spin-label EPR on alpha-synuclein reveals differences in the membrane binding affinity of the two antiparallel helices.

The putative function of the Parkinson's disease-related protein alpha-Synuclein (alphaS) is thought to involve membrane binding. Therefore, the interaction of alphaS with membranes composed of zwitterionic (POPC) and anionic (POPG) lipids was investigated through the mobility of spin labels attached to the protein. Differently labelled variants of alphaS were produced, containing a spin label at positions 9, 18 (both helix 1), 69, 90 (both helix 2), and 140 (C terminus).

Antiparallel arrangement of the helices of vesicle-bound alpha-synuclein.

alpha-Synuclein (alphaS) is the main component of Lewy bodies from Parkinson's disease. That alphaS binds to membranes is known, but the conformation it adopts is still unclear. Pulsed EPR on doubly spin-labeled variants of alphaS sheds light on the most likely structure.

Tissue transglutaminase modulates alpha-synuclein oligomerization.

We have studied the interaction of the enzyme tissue transglutaminase (tTG), catalyzing cross-link formation between protein-bound glutamine residues and primary amines, with Parkinson's disease-associated alpha-synuclein protein variants at physiologically relevant concentrations. We have, for the first time, determined binding affinities of tTG for wild-type and mutant alpha-synucleins using surface plasmon resonance approaches, revealing high-affinity nanomolar equilibrium dissociation constants. Nanomolar tTG concentrations were sufficient for complete inhibition of fibrillization by effective alpha-synuclein cross-linking, resulting predominantly in intramolecularly cross-linked monomers accompanied by an oligomeric fraction.