University of Milano-Bicocca

About: University of Milano-Bicocca is a education organization based out in Milan, Italy. It is known for research contribution in the topics: Population & Blood pressure. The organization has 8972 authors who have published 22322 publications receiving 620484 citations. The organization is also known as: Università degli Studi di Milano-Bicocca & Universita degli Studi di Milano-Bicocca.

Blood pressure variability: its measurement and significance in hypertension.

Abstract: The occurrence of blood pressure fluctuations over time has been documented since the 18th century, but the clinical importance of this phenomenon is only now being recognized. The introduction of ambulatory blood pressure monitoring in the late 1960s represented a major step forward in the study of blood pressure behaviour and helped to characterize the relationship between blood pressure variability and cardiovascular disease. In hypertension, blood pressure variability increases with increasing blood pressure and correlates closely with target-organ damage, independently of absolute blood pressure values. This has important consequences for treatment, which in the past has focused on reducing mean blood pressure values as the main goal. Experimental evidence suggests that drugs capable of buffering or reducing blood pressure variability may confer additional benefits on target-organ protection. Effective target-organ protection could best be afforded by antihypertensive agents that provide efficient 24-h blood pressure control and also stabilize blood pressure variability. Mathematical indices, such as the trough:peak ratio and the smoothness index, provide useful measures of the homogeneity of the antihypertensive effect over 24 h; optimum control is provided by drugs with a trough:peak ratio close to 1 and a smoothness index > 1, as is observed with long-acting drugs such as telmisartan or amlodipine. Recently, a direct relationship was demonstrated between homogeneous blood pressure control and treatment-induced regression of left ventricular hypertrophy, emphasizing the importance of smooth 24-h blood pressure control. In conclusion, the goals of antihypertensive treatment should consider the reduction of both 24-h mean blood pressure and its variability. Long-lasting drugs or drug combinations are preferable to ensure a homogeneous and smooth 24-h blood pressure profile.

hERG1 channels are overexpressed in glioblastoma multiforme and modulate VEGF secretion in glioblastoma cell lines

Abstract: Recent studies have led to considerable advancement in our understanding of the molecular mechanisms that underlie the relentless cell growth and invasiveness of human gliomas. Partial understanding of these mechanisms has (1) improved the classification for gliomas, by identifying prognostic subgroups, and (2) pointed to novel potential therapeutic targets. Some classes of ion channels have turned out to be involved in the pathogenesis and malignancy of gliomas. We studied the expression and properties of K+ channels in primary cultures obtained from surgical specimens: human ether a go-go related (hERG)1 voltage-dependent K+ channels, which have been found to be overexpressed in various human cancers, and human ether a go-go-like 2 channels, that share many of hERG1's biophysical features. The expression pattern of these two channels was compared to that of the classical inward rectifying K+ channels, IRK, that are widely expressed in astrocytic cells and classically considered a marker of astrocytic differentiation. In our study, hERG1 was found to be specifically overexpressed in high-grade astrocytomas, that is, glioblastoma multiforme (GBM). In addition, we present evidence that, in GBM cell lines, hERG1 channel activity actively contributes to malignancy by promoting vascular endothelial growth factor secretion, thus stimulating the neoangiogenesis typical of high-grade gliomas. Our data provide important confirmation for studies proposing the hERG1 channel as a molecular marker of tumour progression and a possible target for novel anticancer therapies.

Metabolism of Phosphatidylinositol 4-Kinase IIIα-Dependent PI4P Is Subverted by HCV and Is Targeted by a 4-Anilino Quinazoline with Antiviral Activity

Abstract: 4-anilino quinazolines have been identified as inhibitors of HCV replication. The target of this class of compounds was proposed to be the viral protein NS5A, although unequivocal proof has never been presented. A 4-anilino quinazoline moiety is often found in kinase inhibitors, leading us to formulate the hypothesis that the anti-HCV activity displayed by these compounds might be due to inhibition of a cellular kinase. Type III phosphatidylinositol 4-kinase α (PI4KIIIα) has recently been identified as a host factor for HCV replication. We therefore evaluated AL-9, a compound prototypical of the 4-anilino quinazoline class, on selected phosphatidylinositol kinases. AL-9 inhibited purified PI4KIIIα and, to a lesser extent, PI4KIIIβ. In Huh7.5 cells, PI4KIIIα is responsible for the phosphatidylinositol-4 phosphate (PI4P) pool present in the plasma membrane. Accordingly, we observed a gradual decrease of PI4P in the plasma membrane upon incubation with AL-9, indicating that this agent inhibits PI4KIIIα also in living cells. Conversely, AL-9 did not affect the level of PI4P in the Golgi membrane, suggesting that the PI4KIIIβ isoform was not significantly inhibited under our experimental conditions. Incubation of cells expressing HCV proteins with AL-9 induced abnormally large clusters of NS5A, a phenomenon previously observed upon silencing PI4KIIIα by RNA interference. In light of our findings, we propose that the antiviral effect of 4-anilino quinazoline compounds is mediated by the inhibition of PI4KIIIα and the consequent depletion of PI4P required for the HCV membranous web. In addition, we noted that HCV has a profound effect on cellular PI4P distribution, causing significant enrichment of PI4P in the HCV-membranous web and a concomitant depletion of PI4P in the plasma membrane. This observation implies that HCV – by recruiting PI4KIIIα in the RNA replication complex – hijacks PI4P metabolism, ultimately resulting in a markedly altered subcellular distribution of the PI4KIIIα product.