University of Palermo

About: University of Palermo is a education organization based out in Palermo, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 15621 authors who have published 40250 publications receiving 964384 citations. The organization is also known as: Università degli Studi di Palermo & Universita degli Studi di Palermo.

Normal-sodium diet compared with low-sodium diet in compensated congestive heart failure: is sodium an old enemy or a new friend?

Abstract: The aim of the present study was to evaluate the effects of a normal-sodium (120 mmol sodium) diet compared with a low-sodium diet (80 mmol sodium) on readmissions for CHF (congestive heart failure) during 180 days of follow-up in compensated patients with CHF. A total of 232 compensated CHF patients (88 female and 144 male; New York Heart Association class II-IV; 55-83 years of age, ejection fraction <35% and serum creatinine <2 mg/dl) were randomized into two groups: group 1 contained 118 patients (45 females and 73 males) receiving a normal-sodium diet plus oral furosemide [250-500 mg, b.i.d. (twice a day)]; and group 2 contained 114 patients (43 females and 71 males) receiving a low-sodium diet plus oral furosemide (250-500 mg, b.i.d.). The treatment was given at 30 days after discharge and for 180 days, in association with a fluid intake of 1000 ml per day. Signs of CHF, body weight, blood pressure, heart rate, laboratory parameters, ECG, echocardiogram, levels of BNP (brain natriuretic peptide) and aldosterone levels, and PRA (plasma renin activity) were examined at baseline (30 days after discharge) and after 180 days. The normal-sodium group had a significant reduction (P<0.05) in readmissions. BNP values were lower in the normal-sodium group compared with the low sodium group (685+/-255 compared with 425+/-125 pg/ml respectively; P<0.0001). Significant (P<0.0001) increases in aldosterone and PRA were observed in the low-sodium group during follow-up, whereas the normal-sodium group had a small significant reduction (P=0.039) in aldosterone levels and no significant difference in PRA. After 180 days of follow-up, aldosterone levels and PRA were significantly (P<0.0001) higher in the low-sodium group. The normal-sodium group had a lower incidence of rehospitalization during follow-up and a significant decrease in plasma BNP and aldosterone levels, and PRA. The results of the present study show that a normal-sodium diet improves outcome, and sodium depletion has detrimental renal and neurohormonal effects with worse clinical outcome in compensated CHF patients. Further studies are required to determine if this is due to a high dose of diuretic or the low-sodium diet.

Exosomes released by K562 chronic myeloid leukemia cells promote angiogenesis in a src-dependent fashion

Abstract: Exosomes, microvesicles of endocytic origin released by normal and tumor cells, play an important role in cell-to-cell communication. Angiogenesis has been shown to regulate progression of chronic myeloid leukemia (CML). The mechanism through which this happens has not been elucidated. We isolated and characterized exosomes from K562 CML cells and evaluated their effects on human umbilical endothelial cells (HUVECs). Fluorescent-labeled exosomes were internalized by HUVECs during tubular differentiation on Matrigel. Exosome localization was perinuclear early in differentiation, moving peripherally in cells undergoing elongation and connection. Exosomes move within and between nanotubular structures connecting the remodeling endothelial cells. They stimulated angiotube formation over a serum/growth factor-limited medium control, doubling total cumulative tube length (P = 0.003). Treatment of K562 cells with two clinically active tyrosine kinase inhibitors, imatinib and dasatinib, reduced their total exosome release (P < 0.009); equivalent concentrations of drug-treated exosomes induced a similar extent of tubular differentiation. However, dasatinib treatment of HUVECs markedly inhibited HUVEC response to drug control CML exosomes (P < 0.002). In an in vivo mouse Matrigel plug model angiogenesis was induced by K562 exosomes and abrogated by oral dasatinib treatment (P < 0.01). K562 exosomes induced dasatinib-sensitive Src phosphorylation and activation of downstream Src pathway proteins in HUVECs. Imatinib was minimally active against exosome stimulation of HUVEC cell differentiation and signaling. Thus, CML cell-derived exosomes induce angiogenic activity in HUVEC cells. The inhibitory effect of dasatinib on exosome production and vascular differentiation and signaling reveals a key role for Src in both the leukemia and its microenvironment.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead

Abstract: Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.