University of Cagliari

About: University of Cagliari is a education organization based out in Cagliari, Italy. It is known for research contribution in the topics: Population & Dopamine. The organization has 11029 authors who have published 29046 publications receiving 771023 citations. The organization is also known as: Università degli Studi di Cagliari & Universita degli Studi di Cagliari.

Early Epirubicin-Induced Myocardial Dysfunction Revealed by Serial Tissue Doppler Echocardiography: Correlation with Inflammatory and Oxidative Stress Markers

Abstract: A phase II, open, nonrandomized trial was carried out in a group of epirubicin-treated patients with cancer at different sites with the aim of detecting early preclinical changes that are predictive of the risk for heart failure. All patients underwent conventional echocardiography, as well as tissue Doppler imaging (TDI) with strain (sigma) and strain rate (SR), a very accurate technique for detecting minimal changes in cardiac left ventricular (LV) function. Moreover, echocardiographic changes identified during epirubicin treatment were compared with those of a series of biochemical markers of both myocardial damage and inflammation/oxidative stress. Sixteen patients (male-to-female ratio, 3:13; mean age +/- standard deviation, 56 +/-3 years; range, 27-75 years) with histologically confirmed tumors at different sites, scheduled to be treated with an epirubicin-based chemotherapy regimen, were enrolled in the study. A significant impairment in systolic LV function was observed after 200 mg/m2 of epirubicin; this was shown by a lower SR peak compared with baseline (1.82 +/- 0.57/second versus 1.45 +/- 0.44/second), whereas sigma remained unchanged. The following significant changes in LV diastolic function occurred only after 300 mg/m2 of epirubicin: a decrease in conventional early/late diastolic (E/A) velocities (1.16 +/- 0.31 versus 0.93 +/- 0.24) and a reduction in both the E(m) wave in the basal portion of the interventricular septum (8.86 +/- 1.73 cm/second versus 7.51 +/- 2.30 cm/second) and in the E(m)/A(m) ratio (1.09 +/- 0.51 versus 0.83 +/- 0.51), as measured using the TDI technique. No significant changes in LV ejection fraction were observed. Baseline values of brain natriuretic peptide, troponin I, myoglobin, and creatine kinase-myocardial subfraction were within the normal range and no significant changes were observed throughout the study. Levels of interleukin (IL)-6 and its soluble receptor (sIL-6R) and reactive oxygen species increased significantly, whereas glutathione peroxidase (GPx) levels decreased significantly, after 200 mg/m2 of epirubicin. Significant correlations between the reduction in the SR peak (deltaSR) after 200 mg/m2 of epirubicin and the increase in IL-6 and ROS and decrease in GPx were observed. The multiple regression analysis showed that the only independent predictive variable for deltaSR was ROS level. Our data show that: (a) subtle cardiac abnormalities may occur at epirubicin doses significantly below those known to be potentially clinically harmful and (b) the earliest myocardial impairment affects LV systolic rather than diastolic function. Early contractility impairment during epirubicin treatment was associated with high levels of ROS and markers of inflammation. The clinical meaningfulness of our findings warrants further investigations in a larger number of patients for a longer period of follow-up.

Increase in meso‐prefrontal dopaminergic activity after stimulation of CB1 receptors by cannabinoids

Abstract: The intravenous administration of the psychoactive constituent of marijuana, delta9-tetrahydrocannabinol (delta9-THC) (62.5-1000 microg/kg), and the synthetic cannabinoid agonist WIN 55212,2 (WIN) (62.5-500 microg/kg), produced a dose-related increase in the firing rate and burst firing in the majority of antidromically identified meso-prefrontal dopaminergic neurons. In a restricted number of neurons (n=4), WIN administration did not increase firing rate but produced an increment of bursting activity. These effects of the cannabinoids were reversed by the intravenous administration of SR 141716 A, a selective cannabinoid antagonist (1 mg/kg), per se ineffective to modify the electrical activity of dopaminergic neurons. The results indicate that stimulation of cannabinoid CB1 receptors produces an activation of meso-prefrontal dopaminergic transmission. Considering that supranormal stimulation of D1 dopamine receptors in the prefrontal cortex has been shown to impair working memory, the present results suggest that the negative effects of cannabinoids on cognitive processes might be related to the activation of dopaminergic transmission in the prefrontal cortex.

Multiple sclerosis in Sardinia is associated and in linkage disequilibrium with HLA-DR3 and -DR4 alleles.

Abstract: The preponderance of genetic factors in attempts to account for susceptibility to multiple sclerosis (MS), a common inflammatory and demyelinating disease of young adults, has recently been demonstrated (Ebers et al . 1995). The inheritance of MS appears to be complex and is believed to involve several genes (Ebers et al . 1996; The Multiple Sclerosis Genetics Group 1996; Sawcer et al . 1996). Methodological approaches to the study of genes conferring susceptibility to MS include association studies, which measure the frequency of a specific allele in affected and healthy populations, and linkage studies, which trace the inheritance of a gene from parents and correlate these genes to disease susceptibility.

Scattering from natural rough surfaces modeled by fractional Brownian motion two-dimensional processes

Abstract: A model for electromagnetic scattering from natural rough surfaces described by means of fractional Brownian motion model is developed. The fractal surface model is employed to obtain the Kirchhoff solution of the Stratton-Chu scattering integral. An analytical viable formulation is achieved and compared to available classical solutions. Comparison with experimental data is also provided. Results show advantages of proposed solution from both theoretical and experimental viewpoint.

Sustained activation of the Raf/MEK/Erk pathway in response to EGF in stable cell lines expressing the Hepatitis C Virus (HCV) core protein

Abstract: Chronic hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. The HCV capside core is a multifunctional protein with regulatory functions that affects transcription and cell growth in vitro and in vivo. Here, we show that both HCV genotype 1a and 3 core proteins activate MEK1 and Erk1/2 MAP kinases and that the costitutive expression of the HCV core results in a high basal activity of Raf1 and MAP/kinase/kinase, as determined by endogenous Raf1 in vitro kinase assay and immunodetection of hyperphosphorylated Erk1 and Erk2 even after a serum starvation. Moreover, the activation of both Erk1/2 and the downstream transcription factor Elk-1 in response to the mitogenic stimulus EGF is significantly prolonged. The sustained response to EGF in cells expressing the HCV core occurs despite a normal induction of the MAP phosphatases MKP regulatory feedback and is likely due to the costitutive activation of Raf-1 activity. The ability of HCV core proteins to directly activate the MAP kinase cascade and to prolong its activity in response to mitogenic stimuli may contribute to the neoplastic transformation of HCV infected liver cells.