Interactions of hydrophilic quantum dots with defect-free and defect containing supported lipid membranes.

Quantum dots (QDs) are semiconductor nanoparticles with unique optical and electronic properties, whose interest as potential nano-theranostic platforms for imaging and sensing is increasing. The design and use of QDs requires the understanding of cell-nanoparticle interactions at a microscopic and nanoscale level. Model systems such as supported lipid bilayers (SLBs) are useful, less complex platforms mimicking physico-chemical properties of cell membranes. In this work, we investigated the effect of topographical homogeneity of SLBs bearing different surface charge in the adsorption of hydrophilic QDs. Using quartz-crystal microbalance, a label-free surface sensitive technique, we show significant differences in the interactions of QDs onto homogeneous and inhomogeneous SLBs formed following different strategies. Within short time scales, QDs adsorb onto topographically homogeneous, defect-free SLBs is driven by electrostatic interactions, leading to no layer disruption. After prolonged QD exposure, the nanomechanical stability of the SLB decreases suggesting nanoparticle insertion. In the case of inhomogeneous, defect containing layers, QDs target preferentially membrane defects, driven by a subtle interplay of electrostatic and entropic effects, inducing local vesicle rupture and QD insertion at membrane edges.

GM1 Ganglioside role in the interaction of Alpha-synuclein with lipid membranes: Morphology and structure.

Alpha-Synuclein (AS) is the protein playing the major role in Parkinson's disease (PD), a neurological disorder characterized by the degeneration of dopaminergic neurons and the accumulation of AS into amyloid plaques. The aggregation of AS into intermediate aggregates, called oligomers, and their pathological relation with biological membranes are considered key steps in the development and progression of the disease. Here we propose a multi-technique approach to study the effects of AS in its monomeric and oligomeric forms on artificial lipid membranes containing GM1 ganglioside. GM1 is a component of functional membrane micro-domains, called lipid rafts, and has been demonstrated to bind AS in neurons. With the aim to understand the relation between gangliosides and AS, here we exploit the complementarity of microscopy (Atomic Force Microscopy) and neutron scattering (Small Angle Neutron Scattering and Neutron Reflectometry) techniques to analyze the structural changes of two different membranes (Phosphatidylcholine and Phosphatidylcholine/GM1) upon binding with AS. We observe the monomer- and oligomer-interactions are both limited to the external membrane leaflet and that the presence of ganglioside leads to a stronger interaction of the membranes and AS in its monomeric and oligomeric forms with a stronger aggressiveness in the latter. These results support the hypothesis of the critical role of lipid rafts not only in the biofunctioning of the protein, but even in the development and the progression of the Parkinson's disease.

Atomic force microscopy analysis of extracellular vesicles.

Extracellular vesicles (EVs) are small vesicles ensuring transport of molecules between cells and throughout the body. EVs contain cell type-specific signatures and have been proposed as biomarkers in a variety of diseases. Their small size (<1 µm) and biological and physical functions make them obvious candidates for therapeutic agents in immune therapy, vaccination, regenerative medicine and drug delivery. However, due to the complexity and heterogeneity of their origin and composition, the actual mechanism through which these vesicles exert their functions is still unknown and represents a great biomedical challenge. Moreover, because of their small dimensions, the quantification, size distribution and biophysical characterization of these particles are challenging and still subject to controversy. Here, we address the advantage of atomic force microscopy (AFM), for the characterization of isolated EVs. We review AFM imaging of EVs immobilized on different substrates (mica, glass) to identify the influence of isolation and deposition methods on the size distribution, morphology and mechanical properties of EVs.

Left ventricular performance in the early stages of systemic hypertension. HARVEST Study Group. Hypertension and Ambulatory Recording Venetia Study.

To investigate whether and how frequently left ventricular (LV) systolic performance assessed with endocardial and midwall measurement is depressed in young subjects with mild systemic hypertension, we studied 722 borderline to mild hypertensive patients (mean age +/- SEM 33 +/- 0.3 years, mean office blood pressure (BP) 146 +/- 0.4/94 +/- 0.2 mm Hg) enrolled in the Hypertension and Ambulatory Recording Venetia Study and 50 normotensive controls with similar age and sex distribution. BP was measured with 24-hour ambulatory monitoring. LV dimensional and functional indexes were assessed by M-mode echocardiography and sympathetic activity from 24-hour urinary catecholamines. In 64 hypertensive subjects (8.9%) the LV midwall shortening-stress relation was < 95% of the confidence interval in 50 normotensive controls. Subjects with depressed LV myocardial function had age, duration of hypertension, and LV mass similar to those of hypertensives with normal performance, and greater relative wall thickness (0.42 vs 0.37, p < 0.001). Stroke volume and cardiac output were lower (p < 0.001) in the former group. Among these 64 subjects, endocardial performance was depressed in 35 (group 1) and normal in 29 (group 2). Group 2 subjects had greater posterior wall (10.0 vs 9.5 mm, p = 0.03), ventricular septum (10.6 vs 10.1 mm, p = 0.05), and relative wall (0.44 vs 0.40, p < 0.001) thicknesses than group 1 subjects. Urinary norepinephrine was 50% higher in group 2 subjects (106 vs 70 g/24 hours, p = 0.03). Stroke volume and cardiac output were similar in both groups. In conclusion, these results show that LV contractility may be depressed in young subjects with borderline to mild hypertension.

Target organ damage and ambulatory blood pressure in stage I hypertension. The Hypertension and Ambulatory Recording Venetia Study.

According to recent international guidelines the decision on whether to treat young subjects during the early phase of hypertension should be based not only on their office blood pressure but also on their ambulatory blood pressure and whether target organ damage has occurred. Few data on the prevalence of hypertensive complications in young subjects with mild hypertension are available. In the Hypertension and Ambulatory Recording Venetia Study (HARVEST), a multicenter trial conducted in northeast Italy, the percentage of young borderline-to-mild hypertensive subjects with echocardiographic left ventricular hypertrophy was 4.5% and the percentage with concentric remodeling was 4%. Clear differences in cardiac size and geometric adjustment to ambulatory systolic pressure between the two sexes were found. The impact of blood pressure on the walls of the left ventricle and on the left ventricular mass was remarkable in women but weak in men. The assessment of left ventricular systolic function confirmed that many young mild hypertensive subjects have an increased ejective performance. The left ventricular contractility evaluated by midwall measurement was, however, found to be depressed in 9.2% of the HARVEST participants. Their left ventricular diastolic function was similar to that of 50 normotensive controls. The prevalence of microalbuminuria [albumin excretion rate (AER) > 30 mg/24 h) was 6.1%, only slightly higher than that found by other authors among normotensive subjects and much lower than that observed among patients with more severe hypertension. For our stage I hypertensives, however, the AER was correlated to the 24 h blood pressure with high statistical significance, whereas we found no relationship between the AER and left ventricular mass index either for all of the subjects taken together or for the men and women considered separately. The results suggest that renal and cardiac involvement do not occur in parallel during the initial phase of hypertension.

[Secondary prevention of myocardial ischemia. From theory to clinical reality: preliminary results of the EUROASPIRE study in Italy. European Action on Secondary Prevention through Intervention to Reduce Events]. / Prevenzione secondaria della cardiopatia ischemica. Dalle premesse teoriche alla realtà clinica: risultati iniziali dello studio EUROASPIRE in Italia. European Action on Secondary Prevention through Intervention to Reduce Events.

EUROASPIRE study has been carried out in 9 European countries with the aim of assessing coronary risk factors in high-risk patients admitted to hospital to undergo coronary revascularization procedures (coronary angioplasty or coronary artery bypass grafting) or because of angina or myocardial infarction. The results of the initial stage of the study in Italy, investigating the data from 691 hospital medical records, showed that management of risk factors in these patients was inferior than expected. In particular, the prevalence of hyperlipidaemia (63%), hypertension (40%) and diabetes (27%) was remarkably high. These results suggest that there is still a need for secondary prevention of coronary heart disease.

Time course of changes in blood pressure, aldosterone and body fluids during enalapril treatment: a double-blind randomized study vs hydrochlorothiazide plus propranolol in essential hypertension.

Aldosterone suppression is said to play a major role in the long term hypotensive efficacy of angiotensin converting enzyme inhibitors. However, in previous reports from other laboratories, plasma volume has been found mostly increased and sodium balance sometimes positive. The effects of the angiotensin converting enzyme inhibitor enalapril (10-40 mg/day, p.o., for 6 weeks) on blood pressure, body fluid volumes, renal function and plasma aldosterone were compared to those of hydrochlorothiazide (50 mg/day, p.o.) alone for 2 weeks and in association with propranolol (80-160 mg/day, p.o.) for 4 more weeks during a randomized double-blind parallel study in 14 essential hypertensives. Hydrochlorothiazide alone and in combination with propranolol induced slight and not significant change in either blood pressure and body fluids. The maximum hypotensive response to enalapril was achieved only after 2 weeks of continuous treatment possibly because after 1 week the hypotensive efficacy was lessened by a significant (P less than 0.05) fluid retention secondary to a transient and not significant fall in renal perfusion. At this time aldosterone was not significantly changed compared to pretreatment values. After 6 weeks on enalapril, blood pressure was significantly reduced, plasma aldosterone further but not significantly decreased and extracellular fluid volume was normal. These findings indicate that aldosterone suppression contributes to the blood pressure lowering effect of enalapril by offsetting the salt and water retention observed on starting treatment and due to direct vasodilation.

[Dynamic evaluation of the renin-angiotensin system with captopril in screening for renovascular hypertension]. / La valutazione dinamica del sistema renina-angiotensina con il captopril nello screening dell'ipertensione renovascolare.

In 69 hypertensive with suspected renovascular hypertension the response of plasma renin and angiotensin I to a single oral dose of Captopril (Captopril test) was determined. In 15 of the 16 patients found to have renal artery stenosis at angiography and cured by either revascularization or nephrectomy, Captopril stimulated both plasma renin activity and plasma angiotensin I to a far greater extent than in the majority of the 53 classified as essential hypertensives. False positives were limited to 8. Sensitivity and specificity were 94% and 85%, respectively. In the same series sequential renal angiophotoscan showed 100% sensitivity but a lower specificity (75%). In comparison, both the sensitivity and the specificity of rapid-sequence intravenous pielography, isotopic renogram and recumbent plasma renin activity were far less satisfactory. It is concluded that this simple, safe and economical test should be preferred to the other diagnostic procedures in the screening of renovascular hypertension. Its use in combination with renal angiophotoscan improves diagnostic reliability.