Brain microstructural abnormalities correlate with KCC2 downregulation in refractory epilepsy.

Dysregulations in the expression level of Na-K-Cl cotransporter (NKCC1) and K-Cl cotransporter (KCC2) genes have been detected in the brain tissues of patients with refractory epilepsy. Given the importance of these proteins in the determination of Cl equilibrium potential (ECl), evaluation of the expression changes of these transporters might assist in optimizing the diagnostic approaches and therapeutic strategies. The present investigation evaluates the expression level chloride transporters in polymorphonuclear cells and their correlation with microstructural abnormalities. Thirty cases of drug-resistant epilepsy (confirmed with temporal lobe epilepsy diagnosis) fulfilled the considered inclusion criteria. Cases were divided into two groups, one with a detectable MRI lesion (19 participants; right side) and another with no MRI findings (11 participants). Whole-brain voxel-based analysis was performed on diffusion tensor imaging to measure fractional anisotropy and mean diffusivity; neurite orientation dispersion and density imaging was performed to map neurite density index and orientation dispersion index. Our results indicated that fractional anisotropy and mean diffusivity changed in temporal and extratemporal parts of the brain, whereas the changes in neurite density index and orientation dispersion index were exclusively obvious in the temporal lobe. Molecular studies revealed significantly lower levels of KCC2 expression in patients with epilepsy, a finding that remarkably correlated with microstructural changes as well. Our research showed that downregulation of KCC2 and microstructural abnormalities might contribute to the observed refractoriness in temporal lobe epilepsy.

Chitosan coated tungsten trioxide nanoparticles as a contrast agent for X-ray computed tomography.

Recent advances have shown that inorganic nanoparticles (NPs) based on heavy elements are highly appropriate for X-ray computed tomography (CT). In this contribution, tungsten trioxide NPs are prepared by the electrical arc discharge (EAD) method in DI water. The effect of chitosan (CTS) and glutaraldehyde (GTA) as coating and cross-linking agent, respectively, on the hydrodynamic size and zeta potential of prepared tungsten trioxide NPs is investigated. It is found that zeta potential increases by increasing the amounts of CTS. Meanwhile, by increasing the volume of glutaraldehyde (GTA), the final particle size increases whereas the zeta potential deceases. Chitosan coated tungsten trioxide demonstrated no significant cytotoxicity at concentration up to 5mg/mL after 24h. Finally, the X-ray attenuation of prepared chitosan coated tungsten trioxide NPs are higher than Iohexol as the commercially available iodinated contrasting agent at the same concentrations.

Breast cancer cells imaging by targeting methionine transporters with gadolinium-based nanoprobe.

PURPOSE: Early cancer diagnosis using MRI imaging is of high global interest as a non-invasive and powerful modality. In this study, methionine was conjugated on gadolinium-based mesoporous silica nanospheres to evaluate intra-cellular uptake and its accumulation in human breast cancer cells. PROCEDURES: The contrast agent was synthesized and characterized using different techniques including N2 physisorption, thermal gravimetric analysis, dynamic light scattering, and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The intra-cellular uptake of Gd(3+) was measured by ICP-AES, fluorescent microscopy, and flow cytometry. Finally, cellular and tumor MR imaging were performed to determine in vitro and in vivo relaxometry. RESULTS: According to the results, the contrast agents accumulated in tumor cells both in vitro and in vivo. There was no significant cellular toxicity on either normal or cancer cells along with strong intense signal on T 1 compared to the unlabeled cells. CONCLUSIONS: The results showed that the novel contrast agent could become a useful tool in early detection of cancer.

Estimated background doses of [67Ga]-DTPA-USPIO in normal Balb/c mice as a potential therapeutic agent for liver and spleen cancers.

INTRODUCTION: The aim of this study was to evaluate the biodistribution of dextran-coated iron oxide nanoparticles labeled with gallium-67 (Ga) in various organs by intravenous injection in Balb/c mice. METHODS: Ultrasmall superparamagnetic iron oxide (USPIO) was successively labeled with Ga-chloride after chelation with freshly prepared cyclic DTPA-dianhydride. The labeling efficiency of USPIOs labeled with Ga is above 98%. Sixty-five mice were killed at 13 different time points. The percentage of injected dose per gram of each organ was measured by direct counting for 19 harvested organs of the mice. The medical internal radiation dose formula was applied to extrapolate data from mouse to human and to predict the absorbed radiation dose for various organs in the human body. RESULTS: The biodistribution of Ga-USPIO in Balb/c mice showed that 75% of the injected dose accumulated in the spleen and liver 15 min after injection. These nanoparticles remained in the liver for more than 7 days after injection, whereas their clearance was very fast from other organs. Extrapolating these data to the intravenous injection of Ga-USPIO in humans gave an estimated absorbed dose of 36.38 mSv/MBq for the total body, and the highest effective absorbed dose was seen in the liver (32.9 mSv/MBq). CONCLUSION: High uptakes of USPIO nanoparticles in the liver and spleen and their fast clearance from other tissues suggest that these nanoparticles labeled with a ß-emitter radioisotope could be suitable as treatment agents for spleen and liver malignancies only if the organ tolerance dose is not exceeded.

Potential use of nanoparticle based contrast agents in MRI: a molecular imaging perspective.

The development of molecular imaging technologies represents the opportunity to differentiate tissues based upon their metabolic and functional activity rather than structural and anatomic characteristics. The goal of molecular imaging is to reveal the pathophysiology underlying the observed anatomy and to diagnose disease based upon early biochemical processes. Detection of pathologic biomarkers can lead to early recognition of diseases, better therapeutic management, and improved monitoring for recurrence. Among the current clinical imaging modalities, MRI is uniquely suited for molecular imaging applications, offering a non-invasive means to obtain both anatomic and metabolic/functional information with high spatial and temporal resolution. Site-specific MRI contrast agents have been developed to target biologic processes that occur early in the development of diseases such as atherosclerotic plaques, tumor angiogenesis, and disease specific biosignatures. Furthermore, early disease recognition, prompting therapeutic intervention and drug delivery evaluation are possible using targeted contrast agents.

Application of small angle X-ray scattering (SAXS) for differentiation between normal and cancerous breast tissue.

INTRODUCTION: Small angle, between 3 degrees and 10 degrees, X ray scattering is predominantly coherent giving rise to diffraction effects that can be observed as constructive and destructive interferences. These interferences carry information about the molecular structure of the tissue and hence can be used to identify changes that occur due to cancer. METHOD: In this study an energy dispersive X-ray diffraction method was used. The optimum scattering angle, determined from a series of measurements on adipose breast tissue at several angles from 4 to 7.3 degrees, was found to be 6.5 degrees. Once optimized the system was used to measure the diffraction profiles (corrected scattered intensity versus momentum transfer) of a total of 99 breast tissue samples. The samples were both normal and tumour samples. RESULTS: Adipose tissue showed a sharp, high intensity peak at low momentum transfer values of approximately 1.1nm-1. Adipose tissue, mixed tissue (adipose & fibroglandular) and tumor have peaks at different values of momentum transfer that can be used to identify the tissue. Benign and malignant breast tissues can also be differentiated by both peak positions and peak heights. It was also observed that the results were reproducible even after the tissue had been preserved at liquid nitrogen temperatures. CONCLUSION: We were able to differentiate between normal, benign and malignant breast tissues by using energy dispersive small angle x-ray scattering.