Polymeric capsules with a thick shell made of biodegradable and biocompatible polymer and a liquid core of perfluorooctyl bromide (PFOB) were evaluated for stability as well as for ultrasound and magnetic resonance imaging (MRI) contrast enhancement. The method of preparation allows the mean capsule diameter to be regulated between 70 nm and 25 µm and the capsule thickness‐to‐radius ratio from 0.25 to 0.54. Capsule diameter remains stable at 37 °C in phosphate buffer for at least 4 and 6 h for nanocapsules and microcapsules, respectively. The in vitro ultrasound signal‐to‐noise ratio (SNR) was measured from 40 to 60 MHz for 6 µm and 150 nm capsules: the SNR increases with capsule concentration up to 20–25 mg mL−1, and then reaches a plateau that depends on capsule diameter (13.5 ± 1.5 dB for 6 µm and 6 ± 2 dB for the 150 nm capsules). The ultrasound SNR is stable for up to 20 min for microcapsules and for several hours for nanocapsules. For nanocapsules, the thinner the shell, the larger the SNR and the more compressible the capsules. Nanocapsule suspensions imaged in vitro with a commercial ultrasound imaging system (normal and tissue harmonic imaging modes, 7–14 MHz probe) were detected down to concentrations of 12.5 mg mL−1. Injections of nanocapsules (200 µg ml−1) in mice in vivo reveal that the initial bolus passage presents significant ultrasound enhancement of the blood pool during hepatic imaging (7–14 MHz probe, tissue harmonic imaging mode). 19F‐MRI images were obtained in vitro at 9.4T using spin‐echo and gradient echo sequences and allow detecting nanocapsules in suspension (50 mg mL−1). In conclusion, these results show initial feasibility for development of these capsules toward a dual‐modality contrast agent.

Itaconate biosynthesis was studied in intact cells of high-yield (RC4) and low-yield (CM85J) strains of the fungus Aspergillus terreus by methods (tracers, nuclear magnetic resonance spectroscopy, and mass spectroscopy) that did not interfere with metabolism. Itaconate formation in RC4 required de novo protein biosynthesis. Krebs cycle intermediates increased in both strains during the production of itaconic acid. The Embden-Meyerhof-Parnas pathway and the Krebs cycle were shown to be involved in this biosynthesis by using 14 C-and 13 C-labelled substrates and nuclear magnetic resonance spectroscopy. A metabolic pathway for itaconate formation from glucose in A. terreus is proposed.

It is generally believed that the apparent diffusion coefficient (ADC) changes measured by diffusion-weighted imaging (DWI) in brain pathologies are related to alterations in the water compartments. The aim of this study was to elucidate the role of compartmentalization in DWI via biexponential analysis of the signal decay due to diffusion. DWI experiments were performed on mouse brain over an extended range of b-values (up to 10000 mm -2 s) under intact, global ischemic, and cold-injury conditions. DWI was additionally applied to centrifuged human erythrocyte samples with a negligible extracellular space. Biexponential signal decay was found to occur in the cortex of the intact mouse brain. During global ischemia, in addition to a drop in the ADC in both components, a shift from the volume fraction of the rapidly diffusing component to the slowly diffusing one was observed. In cold injury, the biexponential signal decay was still present despite the electron-microscopically validated disintegration of the membranes. The biexponential function was also applicable for fitting of the data obtained on erythrocyte samples Diffusion-weighted imaging (DWI) and measurements of the apparent diffusion coefficient (ADC) play important roles in clinical diagnosis. Alterations in the ADC of water occur in many pathological conditions, such as stroke (1,2), diffuse axonal injury (3), tumors (4), and epilepsy (5). Nevertheless, despite the widespread use of DWI, the underlying mechanisms that cause these changes in ADC are still unclear. Many theories have been put forward to explain the phenomenon, including: 1) water shifts from the extracellular space to the more viscous intracellular space (2,6,7); 2) a loss of cytoplasmic streaming and/or an increased intracellular viscosity results in a drop in ADC (8,9); 3) the extracellular space becomes more tortuous during such a water shift (10 -12); and 4) water goes through a transition from a sol state to a gel state (13).It is clear that, with exception of the latter theory, the physiological compartments appear to be involved. Van Zijl et al. (14) reported evidence suggesting that complete separation of the intra-and extracellular spaces in cell cultures was feasible by means of DW spectroscopy. However, the work of Niendorf et al. (15) on rat brain indicated that the correspondence between the water populations determined in vivo by localized DW spectroscopy and the extra-and intracellular compartments is not straightforward. Nevertheless, several studies involving experimental models (15-17) have indicated that the changes in these volume fractions, as assessed by NMR, follow the alterations in the water compartments in the brain. It becomes more difficult to understand the diffusion properties of water molecules in nervous tissue when the b-value range is extended over 10000 mm -2 s, where more than two exponentially decaying components can be determined (18).The results of the above-cited studies indicate that the origin of the water signal and the multiexponential funct...

BackgroundTNF-related lymphotoxin α (LTα) is essential for the development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM). The pathway involved has been attributed to TNFR2. Here we show a second arm of LTα-signaling essential for ECM development through LTβ-R, receptor of LTα1β2 heterotrimer.Methodology/Principal FindingsLTβR deficient mice did not develop the neurological signs seen in PbA induced ECM but died at three weeks with high parasitaemia and severe anemia like LTαβ deficient mice. Resistance of LTαβ or LTβR deficient mice correlated with unaltered cerebral microcirculation and absence of ischemia, as documented by magnetic resonance imaging and angiography, associated with lack of microvascular obstruction, while wild-type mice developed distinct microvascular pathology. Recruitment and activation of perforin+ CD8+ T cells, and their ICAM-1 expression were clearly attenuated in the brain of resistant mice. An essential contribution of LIGHT, another LTβR ligand, could be excluded, as LIGHT deficient mice rapidly succumbed to ECM.Conclusions/SignificanceLTβR expressed on radioresistant resident stromal, probably endothelial cells, rather than hematopoietic cells, are essential for the development of ECM, as assessed by hematopoietic reconstitution experiment. Therefore, the data suggest that both functional LTβR and TNFR2 signaling are required and non-redundant for the development of microvascular pathology resulting in fatal ECM.