Uncinate fasciculus fiber tracking in mesial temporal lobe epilepsy. Initial findings

In temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), ictal discharge spread to the frontal and insulo-perisylvian cortex is commonly observed. The implication of white matter pathways in this propagation has not been investigated. We compared diffusion tensor imaging (DTI) measurements along the uncinate fasciculus (UF), a major tract connecting the frontal and temporal lobes, in patients and controls. Ten right-handed patients referred for intractable TLE due to a right HS were investigated on a 1.5-T MR scanner including a DTI sequence. All patients had interictal fluorodeoxyglucose PET showing an ipsilateral temporal hypometabolism associated with insular and frontal or perisylvian hypometabolism. The controls consisted of ten right-handed healthy subjects. UF fiber tracking was performed, and its fractional anisotropy (FA) values were compared between patients and controls, separately for the right and left UF. The left-minus-right FA UF asymmetry index was computed to test for intergroup differences. Asymmetries were found in the control group with right-greater-than-left FA. This asymmetrical pattern was lost in the patient group. Right FA values were lower in patients with right HS versus controls. Although preliminary, these findings may be related to the preferential pathway of seizure spread from the mesial temporal lobe to frontal and insulo-perisylvian areas.     

On-line desorption of dried blood spot: A novel approach for the direct LC/MS analysis of μ-whole blood samples

The aim of this work is to present a new concept, called on-line desorption of dried blood spots (on-line DBS), allowing the direct analysis of a dried blood spot coupled to liquid chromatography mass spectrometry device (LC/MS). The system is based on an inox cell which can receive a blood sample (10 μL) previously spotted on a filter paper. The cell is then integrated into LC/MS system where the analytes are desorbed out of the paper towards a column switching system ensuring the purification and separation of the compounds before their detection on a single quadrupole MS coupled to atmospheric pressure chemical ionisation (APCI) source. The described procedure implies that no pretreatment is necessary in spite the analysis is based on whole blood sample.     

Characterization of ZK 245186, a novel,selective glucocorticoid receptor agonist for the topical treatment of inflammatory skin diseases

Background and purpose:

Glucocorticoids are highly effective in the therapy of inflammatory diseases. Their value, however, is limited by side effects. The discovery of the molecular mechanisms of the glucocorticoid receptor and the recognition that activation and repression of gene expression could be addressed separately opened the possibility of achieving improved safety profiles by the identification of ligands that predominantly induce repression. Here we report on ZK 245186, a novel, non-steroidal, low-molecular-weight, glucocorticoid receptor-selective agonist for the topical treatment of inflammatory dermatoses.

Experimental approach:

Pharmacological properties of ZK 245186 and reference compounds were studied in terms of their potential anti-inflammatory and side effects in functional bioassays in vitro and in rodent models in vivo.

Key results:

Anti-inflammatory activity of ZK 245186 was demonstrated in in vitro assays for inhibition of cytokine secretion and T cell proliferation. In vivo, using irritant contact dermatitis and T cell-mediated contact allergy models in mice and rats, ZK 245186 showed anti-inflammatory efficacy after topical application similar to the classical glucocorticoids, mometasone furoate and methylprednisolone aceponate. ZK 245186, however, exhibits a better safety profile with regard to growth inhibition and induction of skin atrophy after long-term topical application, thymocyte apoptosis, hyperglycaemia and hepatic tyrosine aminotransferase activity.

Conclusions and implications:

ZK 245186 is a potent anti-inflammatory compound with a lower potential for side effects, compared with classical glucocorticoids. It represents a promising drug candidate and is currently in clinical trials.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Real-time MR diffusion tensor and Q-ball imaging using Kalman filtering

Diffusion magnetic resonance imaging (dMRI) has become an established research tool for the investigation of tissue structure and orientation. In this paper, we present a method for real-time processing of diffusion tensor and Q-ball imaging. The basic idea is to use Kalman filtering framework to fit either the linear tensor or Q-ball model. Because the Kalman filter is designed to be an incremental algorithm, it naturally enables updating the model estimate after the acquisition of any new diffusion-weighted volume. Processing diffusion models and maps during ongoing scans provides a new useful tool for clinicians, especially when it is not possible to predict how long a subject may remain still in the magnet. First, we introduce the general linear models corresponding to the two diffusion tensor and analytical Q-ball models of interest. Then, we present the Kalman filtering framework and we focus on the optimization of the diffusion orientation sets in order to speed up the convergence of the online processing. Last, we give some results on a healthy volunteer for the online tensor and the Q-ball model, and we make some comparisons with the conventional offline techniques used in the literature. We could achieve full real-time for diffusion tensor imaging and deferred time for Q-ball imaging, using a single workstation.