[Experimental studies on pressor reaction of nor-adrenaline infusion during anoxia].
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Biomedical subjects
Publications and source records attributed to G Brotzu.
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Recent studies have shown that a membrane p-glycoprotein, encoded by MDR1 gene, is involved in the transport of free cholesterol from the plasma membrane to endoplasmic reticulum, the site of cholesterol esterification by acyl-CoA:cholesterol acyltransferase (ACAT). Moreover, results deriving from our previous studies have shown that the rate of cell proliferation was positively correlated with cholesteryl ester levels as well as with ACAT and MDR1 gene expression. In this study, lipid content and the expression of the genes involved in cholesterol metabolism such as hydroxy-methylglutaryl coenzyme A reductase (HMGCoA-R), low-density lipoprotein receptor (LDL-R), ACAT and MDR1 have been investigated in control and atherosclerotic arteries. The results have shown that the levels of cholesteryl ester increase with the age of cadaveric donors in arteries prone to atherosclerosis (abdominal aorta, superficial femoral artery) and become predominant in advanced atherosclerotic lesions. The mRNA levels of ACAT and MDR1 showed the same age correlation, reaching the highest values in atherosclerotic specimens. These results suggest that MDR1 may be involved in the accumulation of intracellular cholesterol ester levels found in atherosclerotic lesions. Moreover, the levels of HMGCoA-R, LDL-R and ACAT gene expressions progressively increased with the age of cadaveric donors; conversely, in atherosclerotic specimens, the mRNA levels of HMGCoA-R and LDL-R drastically decreased while ACAT gene expression reached its maximum. These findings suggest a reactivation of normal homeostatic regulation of cholesterol in advanced and complicated lesions.
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Results of clinical islet transplantation remain disappointing despite the advances in islet technology. Availability of human organs and control of rejection by adequate immunosuppressive therapy remain the unsolved problems. Transplantation of xenogeneic tissue enclosed in immuno-separating membranes without immunosuppressive drugs may be a solution. In the present study porcine pancreatic islets were isolated by semiautomated method and purified utilizing discontinuous Euroficoll gradients on IBM 2991 cell separator. The porcine pancreatic islets were encapsulated with a new one-step method utilizing a home-made droplet generator. Each microcapsule contained one or two islets and microcapsule diameter was approximately that of the islets. This condition allows an optimal diffusion of insulin, glucose, nutrients and oxygen. Consequently, perifusion experiments with encapsulated porcine islets revealed a typical biphasic pattern of insulin release as it was seen in unencapsulated controls. Human erythrocytes were encapsulated and incubated with serum containing hemolysins and complement. These experiments showed that the encapsulated erythrocytes were protected against the hemolytic activity of Ig G and complement fractions. In conclusion, this encapsulation procedure allows the production of a very thin barium alginate membrane around the islets with very little increase of the total volume of transplanted tissue.