A decrease in cerebral glucose metabolic uptake is an early and characteristic sign of Alzheimer's disease (AD). Streptozotocin (STZ) is a bacterial toxin which damages insulin-producing cells and insulin receptors. Intracerebroventricular (icv) application of STZ in rats has been found to chronically decrease cerebral glucose uptake and produce other effects that bear a resemblance to several other molecular and pathological features of AD. In the present experiments in vivo (1)H MR Spectroscopy with short echo time (3 ms) was used to non-invasively obtain a neurochemical profile of rat brains, 3 weeks and 2 months after double icv injections of STZ or vehicle. Seventeen metabolites were quantified from 27 microL tissue volume which included hippocampus and a part of cerebral cortex, using the LCModel and unsuppressed water signal as an internal reference. Three weeks after icv STZ several metabolites were significantly decreased, the most prominent changes noted in glycerophosphocholine and phosphocholine (-38 +/- 5%), glutathione (-37 +/- 4%), taurine (-30 +/- 19%), glutamate (-26 +/- 14%), phosphocreatine (-23 +/- 15%) and N-acetylaspartate (-16 +/- 6%). On the contrary, the concentration of N-acetylaspartylglutamate was found significantly increased (+38 +/- 18%). After 2 months some of these changes were even more pronounced. We conclude that in vivo (1)H MRS of rat brain following icv STZ injections provides a new input into a better understanding of the critical dependency of neural function and structure on brain glucose consumption, and may be of relevance in further studies of AD pathomechanism.
In the mouse model of dilated cardiomyopathy, endothelial dysfunction in coronary circulation is present in the late but not the early stage of heart failure pathology and is characterized by a decrease in NO bioavailability and a compensatory increase in PGI(2). Both the decrease in NO activity and the increase in PGI(2) activity may result from excessive O(2) (-) production by cardiac NADPH oxidase in Tgalphaq*44 hearts.
Evaluation of macromolecular polymers used as excipients for the preparation of hydrodynamically balanced systems (HBS) was carried out. Hard gelatine capsules were filled with polymeric substances belonging to various chemical groups (chitosan, sodium alginate, hydroxypropylmethycellulose--HPMC). The following properties of the HBS were investigated: density, hydration, erosion and floating force. The solvent penetration process into the HBS was visualized using magnetic resonance imaging (MRI) technique. Densities of the HBS in hydrochloric acid (0.1 M) ranged from 0.37 g/cm3 to 0.71 g/cm3. Each polymer demonstrated different hydration/erosion abilities and floating properties. The maximum floating force (F(float max)) for capsules size 0, ranged from 26.7 mN (sodium alginate) to 64.7 mN (chitosan). HBS formulations also varied in time to reach maximum floating force (T(float max)). HPMC and sodium alginate formulation reached F(float max) within half an hour after immersion, while in the case of chitosan formulations (deacetylation degree (d.d.) 66% and d.d. 93%), the time was 184 minutes and 218 minutes respectively. The floating properties of the dosage forms were reliant on type of the polymer and the medium-fasted state simulated gastric fluid (FaSSGF) or fed state simulated gastric fluid (FeSSGF). The size of the HBS influenced the floating force value. The mechanisms of erosion and swelling of the polymeric matrices play a dominant role in flotation of the dosage forms.
Rank-2 tensors are unable to represent multi-modal diffusion associated with intra-voxel orientational heterogeneity (IVOH), which occurs where axons are incoherently oriented, such as where bundles intersect or diverge. Under this condition, they are oblate or spheroidally shaped, resulting in artefactually low anisotropy, potentially masking reduced axonal density, myelinisation and integrity. Higher rank tensors can represent multi-modal diffusion, and suitable metrics such as generalised anisotropy (GA) and scaled entropy (SE) have been introduced. The effect of tensor rank was studied through simulations, and analysing high angular resolution diffusion imaging (HARDI) data from two volunteers, fit with rank-2, rank-4 and rank-6 tensors. The variation of GA and SE as a function of rank was investigated through difference maps and region of interest (ROI)-based comparisons. Results were correlated with orientation distribution functions (ODF) reconstructed with q-ball, and with colour-maps of the principal and second eigenvectors. Simulations revealed that rank-4 tensors are able to represent multi-modal diffusion, and that increasing rank further has a minor effect on measurements. IVOH was detected in subcortical regions of the corona radiata, along the superior longitudinal fasciculus, in the radiations of the genu of the corpus callosum, in peritrigonal white matter and along the inferior fronto-occipital and longitudinal fascicula. In these regions, elevating tensor rank increased anisotropy. This was also true for the corpus callosum, cingulum and anterior limb of the internal capsule, where increasing tensor rank resulted in patterns that, although mono-modal, were more anisotropic. In these regions the second eigenvector was coherently oriented. As rank-4 tensors have only 15 distinct elements, they can be determined without acquiring a large number of directions. By removing artefactual underestimation of anisotropy, their use may increase the sensitivity to pathological change.
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