Adiponectin and left ventricular structure and function in healthy adults

CONTEXT: Adiponectin inhibits protein synthesis in cardiac myocytes, thereby opposing the effect of cardiac workload and trophic factors (in particular, insulin) on left ventricular (LV) mass and wall thickness (WT). OBJECTIVE: We tested whether adiponectin and its isoforms are related to LV mass, WT, and function independently of metabolic factors. DESIGN: This was a cross-sectional study. SUBJECTS: The study included 77 healthy volunteers (42 men) aged 30-59 yr with normal LV structure and function. MAIN OUTCOME MEASURES: Insulin response and insulin sensitivity were assessed by oral glucose tolerance test and euglycemic hyperinsulinemic clamp. LV mass, WT, stroke work, chamber function, and myocardial longitudinal function were evaluated by standard Doppler echocardiography and tissue Doppler imaging. Total and molecular isoforms of adiponectin were measured in plasma. RESULTS: By multivariate analysis, independent factors affecting LV mass were sex, body mass index, stroke work, and current smoking (R(2) = 0.66). Independent correlates of LV WT were age, stroke work, and plasma adiponectin (standardized r = 0.28, 0.41, and -0.26, P at least < 0.005, R(2) = 0.48). LV longitudinal late diastolic velocity was independently related to age, body mass index, and adiponectin (standardized r = 0.20, 0.26, -0.33, P at least < 0.05, R(2) = 0.30). High-molecular-weight adiponectin (47% of total), but not lower molecular-weight isoforms, insulin sensitivity, or other metabolic factors, was inversely and independently related to WT (standardized r = -0.27, P < 0.01) and myocardial longitudinal late diastolic velocity (standardized r = -0.28, P < 0.05). CONCLUSION: In healthy subjects, circulating total and high-molecular-weight adiponectin are related to LV WT and diastolic function, independently of age and metabolic factors.     

Discovery of a quorum-sensing inhibitor of drug-resistant staphylococcal infections by structure-based virtual screening

Staphylococci are a major health threat because of increasing resistance to antibiotics. An alternative to antibiotic treatment is preventing virulence by inhibition of bacterial cell-to-cell communication using the quorum-sensing inhibitor RNAIII-inhibiting peptide (RIP). In this work, we identified 2',5-di-O-galloyl-d-hamamelose (hamamelitannin) as a nonpeptide analog of RIP by virtual screening of a RIP-based pharmacophore against a database of commercially available small-molecule compounds. Hamamelitannin is a natural product found in the bark of Hamamelis virginiana (witch hazel), and it has no effect on staphylococcal growth in vitro; but like RIP, it does inhibit the quorum-sensing regulator RNAIII. In a rat graft model, hamamelitannin prevented device-associated infections in vivo, including infections caused by methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis strains. These findings suggest that hamamelitannin may be used as a suppressor to staphylococcal infections.     

Induction of differentiation in human promyelocytic cells by the isothiocyanate sulforaphane

BACKGROUND: The consumption of cruciferous vegetables has long been associated with a reduced risk for the occurrence of cancer at various sites. This protective effect is associated with their isothiocyanate content. Sulforaphane (SFN) is by far the isothiocyanate most extensively studied to uncover the mechanisms behind this chemoprotection. In the present study, the ability of SFN to induce cytodifferentiation and apoptosis in a leukemia cell line was investigated. MATERIALS AND METHODS: Cells were treated with different concentrations of SFN (0-100 microM). Analysis of cell differentiation was performed by nonspecific/specific acid esterase activity. Apoptosis induction was performed by flow cytometry. RESULTS: SFN induced cytodifferentiation toward both granulocytic and macrophagic lineage, mediated by the involvement of phosphatidylinositol 3-kinase/protein kinase C. It also caused a significant increase in the apoptotic cell fraction. CONCLUSION: These findings suggest that SFN may be a promising antileukemic agent and should encourage further investigation as regards its chemotherapeutic potential.     

Saliva analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF/MS): from sample collection to data analysis.

BACKGROUND: Saliva is one of the most promising and easy-to-collect source of potential biomarkers of oral and systemic disease. We standardized a protocol suitable for pre-analytical treatment and for the analysis of whole normal saliva by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF/MS). METHODS: We evaluated the impact of storage time, freeze/thaw cycles, denaturing agents, glycoproteins depletion, centrifugation, type of matrix and ProteinChip used on the quality of the SELDI protein profile. Moreover, we explored the inter-individual and between-sex differences and the changes in the sample composition over the day. RESULTS: Saliva was qualitatively stable, in the absence of protease inhibitors, for up to 3 h from the collection at room temperature, although the intensity of a number of peaks slightly decreased between 0 and 3 h and the addition of protease inhibitors did not completely revert this trend. The saliva proteome changed during the day and showed relevant between-sex differences. The protein profile remained stable for up to five freeze/thaw cycles. The addition of denaturing solutions and the depletion of glycoproteins improved the quality of the spectra without affecting their reproducibility. CONCLUSIONS: We defined a protocol that improved the quality and the reproducibility of SELDI-TOF/MS analysis, thus potentially supporting the search for putative biomarkers of disease.