Vascular ATGL-dependent lipolysis and the activation of cPLA2-PGI2 pathway protect against postprandial endothelial dysfunction.

Adipose triglyceride lipase (ATGL) is involved in lipolysis and displays a detrimental pathophysiological role in cardio-metabolic diseases. However, the organo-protective effects of ATGL-induced lipolysis were also suggested. The aim of this work was to characterize the function of lipid droplets (LDs) and ATGL-induced lipolysis in the regulation of endothelial function. ATGL-dependent LDs hydrolysis and cytosolic phospholipase A2 (cPLA2)-derived eicosanoids production were studied in the aorta, endothelial and smooth muscle cells exposed to exogenous oleic acid (OA) or arachidonic acid (AA). Functional effects of ATGL-dependent lipolysis and subsequent activation of cPLA2/PGI2 pathway were also studied in vivo in relation to postprandial endothelial dysfunction.The formation of LDs was invariably associated with elevated production of endogenous AA-derived prostacyclin (PGI2). In the presence of the inhibitor of ATGL or the inhibitor of cytosolic phospholipase A2, the production of eicosanoids was reduced, with a concomitant increase in the number of LDs. OA administration impaired endothelial barrier integrity in vitro that was further impaired if OA was given together with ATGL inhibitor. Importantly, in vivo, olive oil induced postprandial endothelial dysfunction that was significantly deteriorated by ATGL inhibition, cPLA2 inhibition or by prostacyclin (IP) receptor blockade.In summary, vascular LDs formation induced by exogenous AA or OA was associated with ATGL- and cPLA2-dependent PGI2 production from endogenous AA. The inhibition of ATGL resulted in an impairment of endothelial barrier function in vitro. The inhibition of ATGL-cPLA2-PGI2 dependent pathway resulted in the deterioration of endothelial function upon exposure to olive oil in vivo. In conclusion, vascular ATGL-cPLA2-PGI2 dependent pathway activated by lipid overload and linked to LDs formation in endothelium and smooth muscle cells has a vasoprotective role by counterbalancing detrimental effects of lipid overload on endothelial function.

MR Diffusion Anisotropy Imaging of Spinal Cord Mechanical Compression and Injury on the Rat Model. In Vivo.

The aim of this study was the application of magnetic resonance diffusion anisotropy imaging (MR DAI) for assessment of spinal cord compression (SCC) and injury (SCI) in rats depending on the time course from the moment of injury. Twenty rats were used, divided into three groups (five with no surgical operation, five with laminectomy only and ten with SCI produced using a dynamic weight - drop model). MR DAI was performed four times (1, 24, 48 and 168 hours after surgery) at 4.7 T with diffusion gradients applied parallel and perpendicular to the spine. Diffusion parameters (lADC, tADC and AI) were calculated for defined regions of white and gray matter. Epidural hematoma which appeared after laminectomy compressed spinal cord and caused a decrease of apparent diffusion coefficient (ADC) values in GM and WM. SCI in WM produced a decrease of lADC and increase in tADC. In GM an increase in both lADC and tADC values after SCI was observed. MR DAI will disclose dynamic changes in water diffusion during the first days after spinal cord contusion.

Elevating tensor rank increases anisotropy in brain areas associated with intra-voxel orientational heterogeneity (IVOH): a generalised DTI (GDTI) study.

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.

Risk of malignant tumors in first-degree relatives of patients with differentiated thyroid cancer -- a hospital based study.

In presented study the risk of incidence of familial differentiated thyroid cancer as well as the risk of other malignant tumors in families of DTC patients was evaluated. 999 patients with differentiated thyroid cancer and 825 persons without any history of malignant disease were evaluated on the occurrence of malignant neoplasm within their families. Information about 6614 first degree relatives of DTC index patients and 4939 first degree relatives of control persons were recorded. The incidence of cancers at various sites was compared between first-degree relatives of index patients and control persons and odds ratio with 95% confidence intervals (CI) were calculated for thyroid cancer and other cancer sites. Within 999 families of thyroid cancer index patients 23 families with more than one case of DTC were found. The risk of the development of thyroid cancer in the first degree was 6 (95% CI 1.8-19) times greater in the index group than in the control group. No increased risk for development of other malignancies was observed. Results of our study confirm previous reports of increased risk of thyroid cancer in first-degree relatives of differentiated thyroid cancer patients. However, the relatively small number of first-degree relatives affected with thyroid cancer (24/6614) does not justify at present any screening in the first-degree relatives of patients affected with differentiated thyroid cancer. Simultaneously, no increased risk of other malignant neoplasm was observed in the differentiated cancer families.