PubMed · 14811409
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W WILBRANDT. 1950. [Problems in permeability].. https://pubmed.ncbi.nlm.nih.gov/14811409/
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The lysosomal cysteine protease cathepsin B is implicated in degradation of extracellular matrix (ECM), a crucial step in a variety of physiological and pathological processes, including tumor dissemination and angiogenesis. In this study, we analyzed the contribution of extracellular and intracellular cathepsin B activity on the formation of capillary-like tubular structures by human umbilical vein endothelial cells (HUVECs) grown on Matrigel matrix, using general and specific cysteine protease inhibitors. We demonstrated, by confocal assay using quenched fluorescent protein substrate DQ-collagen IV, that endothelial cells degrade ECM both intracellularly and pericellularly. Intracellular cathepsin B activity detected by degradation of Z-Arg-Arg cresyl violet substrate was co-localized with the products of DQ-collagen IV degradation in the perinuclear region and in the capillary-like tubular structures. Treatment of cells with membrane-permeable CA-074 Me effectively abolished intracellular cathepsin B activity, and resulted in reduced tube length (32.3+/-9.4% at 10 microM), total tubule area (49.6+/-12.4% at 10 microM), and the number of branch points of tubules (47.5+/-7.7% at 10 microM) in a dose-dependent manner. In contrast, CA-074 (0.1-10 microM), a membrane-impermeable cathepsin B specific inhibitor, general cysteine protease inhibitors chicken cystatin (5 microM) and E-64 (10 microM), and the metalloprotease inhibitor Minocycline (10 microM) showed no significant inhibitory effect in our angiogenesis model. These results show that, besides multiple regulatory molecules, intracellular cathepsin B also contributes to the neovascularization process and should be considered as a potential therapeutic target.
AIM: Type 2 diabetes is not only associated with hyperglycemia but also with disorders of lipid metabolism. The aim of this study was to investigate the association of dyslipedemia with micro and macro vascular complications of diabetes. METHODS: Population based cross sectional study included 4067 diabetic patients who visited hospital during January 2000 to December 2002. Lipid profile was estimated by semi autoanalyser, Retinopathy was assessed by fundoscopy, Nephropathy by microalbuminurea, coronary artery disease (CAD) by electro cardiogram (ECG) changes, peripheral vascular disease (PVD) by doppler study and neuropathy by clinical examinations. The association of dyslipedemia with micro and macro vascular complications was assessed by regression analysis. RESULTS: The prevalence of dyslipedemia is high in diabetic population with high serum cholesterol >240mg/dl was seen in 15%, serum triglycerides >160mg/dl was seen in 42.41%, raised LDL >130mg/dl in 45.26%, VLDL >40mg/dl in 24.09% and low levels of HDL-C <40mg/dl were seen in 52.27%. On regression analysis, CAD had strong correlation with high levels of VLDL (0.76), triglycerides (0.82), LDL (0.23) and low HDL (-0.81). Similar association was seen with PVD. Diabetic retinopathy and nephropathy were found to have significant correlation with low HDL (-0.43) and raised LDL (0.37), respectively. Neuropathy was not found to have any significant correlation with lipid profile abnormalities. CONCLUSION: Lipid profile abnormalities are very common in type 2 diabetes and it has great influence on CAD and PVD. Hence, appropriate preventive and treatment strategies should be considered timely.
The processability of giant (macro)molecules into ultrapure and highly ordered structures at surfaces is of fundamental importance for studying chemical, physical and biological phenomena, as well as their exploitation as active units in the fabrication of hybrid devices. The possibility of handling larger and larger molecules provides access to increasingly complex functions. Unfortunately, larger molecules commonly imply lower processability due to either their low solubility in liquid media or the occurrence of thermal cracking during vacuum sublimation. The search for novel strategies to process and characterize giant building blocks is therefore a crucial goal in materials science. Here we describe a new general route to process, at surfaces, extraordinarily large molecules, that is, synthetic nanographenes, into ultrapure crystalline architectures. Our method relies on the soft-landing of ions generated by solvent-free matrix-assisted laser desorption/ionization (MALDI). The nanographenes are transferred to the gas phase, purified and adsorbed at surfaces. Scanning tunnelling microscopy reveals the formation of ordered nanoscale semiconducting supramolecular architectures. The unique flexibility of this approach allows the growth of ultrapure crystalline films of various systems, including organic, inorganic and biological molecules, and therefore it can be of interest for technological applications in the fields of electronics, (bio)catalysis and nanomedicine.