Metal Nanoclusters with Synergistically Engineered Optical and Buffering Activity of Intracellular Reactive Oxygen Species by Compositional and Supramolecular Design.

Metal nanoclusters featuring tunable luminescence and high biocompatibility are receiving attention as fluorescent markers for cellular imaging. The recently discovered ability of gold clusters to scavenge cytotoxic reactive oxygen species (ROS) from the intracellular environment extends their applicability to biomedical theranostics and provides a novel platform for realizing multifunctional luminescent probes with engineered anti-cytotoxic activity for applications in bio-diagnostics and conceivably cellular therapy. This goal could be achieved by using clusters of strongly reactive metals such as silver, provided that strategies are found to enhance their luminescence while simultaneously enabling direct interaction between the metal atoms and the chemical surroundings. In this work, we demonstrate a synergic approach for realizing multifunctional metal clusters combining enhanced luminescence with strong and lasting ROS scavenging activity, based on the fabrication and in situ protection of Ag nanoclusters with a supramolecular mantle of thiolated-Au atoms (Ag/Au-t). Confocal imaging and viability measurements highlight the biocompatibility of Ag/Au-t and their suitability as fluorescent bio-markers. ROS concentration tests reveal the remarkable scavenging activity of Ag-based clusters. Proliferation tests of cells in artificially stressed culture conditions point out their prolonged anti-cytotoxic effect with respect to gold systems, ensuring positive cell proliferation rates even for long incubation time.

Impact of influenza vaccine on response to vaccination with pneumococcal vaccine in HIV patients.

The clinical effectiveness of 23-valent pneumococcal vaccine in human immunodeficiency virus (HIV)-infected patients is controversial, because of the low immunological response in these subjects. We studied the clinical response of pneumococcal vaccine and the relative impact of influenza vaccine by administering both pneumococcal and influenza vaccine in a group of 150 HIV patients belonging to all CDC categories. In the group of 90 HIV-infected patients vaccinated against both pneumonia and influenza virus, there was a low incidence of mild influenza (13.3%) and no case of pneumococcal pneumonia. On the contrary, among 60 nonvaccinated HIV patients, 61.6% underwent mild to severe influenza and two developed pneumococcal pneumonia. 23-valent pneumococcal vaccine (PV) seems to be clinically effective in preventing pneumonia in HIV-infected patients, and even more if strengthened by influenza vaccine.

Ischemic mitral regurgitation: intraventricular papillary muscle imbrication without mitral ring during left ventricular restoration.

OBJECTIVES: Functional mitral regurgitation in ischemic cardiomyopathy carries a poor prognosis, and its surgical management remains problematic and controversial. The aim of this study was to report the results of our surgical approach to patients who have had myocardial infarctions and have ventricular dilatation, mitral regurgitation, reduced pump function, pulmonary hypertension and coronary artery disease. This surgical approach consists of endoventricular mitral repair without prosthetic ring, ventricular reconstruction with or without patch, and coronary artery bypass grafting. PATIENTS: Forty-six patients (aged 64 +/- 10 years) with previous anterior transmural myocardial infarction and mitral regurgitation comprised the study group. Indication for surgery was heart failure in 93% of cases; 25 patients were in New York Heart Association functional class IV and 17 were in class III. Mitral regurgitation was moderate to severe in 32 cases (69%). RESULTS: All patients underwent coronary artery bypass grafting, with a mean of 3.2 +/- 1.3 grafts. Associated aortic valve replacement was performed in 4 cases. Global operative mortality rate was 15.2%. End-diastolic and end-systolic volumes significantly decreased after surgery (from 140 +/- 40 to 98 +/- 36 mL/m(2) and from 98 +/- 32 to 63 +/- 22 mL/m(2), respectively, P =.001). Systolic pulmonary pressure decreased significantly (from 55 +/- 13 to 43 +/- 16 mm Hg, P =.001). Ejection fraction did not change significantly. Postoperative mitral regurgitation was absent or minimal in 84% of cases; 1 patient had severe mitral regurgitation necessitating valve replacement. New York Heart Association functional class significantly improved. The mean preoperative functional class was 3.4 +/- 0.6 (median 3, range 2-4); after the operation, this decreased to 1.9 +/- 0.7 (median 2, range 1-3, P <.001). Cumulative survival at a 30-month follow-up was 63%. CONCLUSIONS: Our aggressive, combined surgical approach is aimed at correcting the three components of ischemic cardiomyopathy: relieving ischemia, reducing left ventricular wall tension by decreasing left ventricular volumes, and reducing volume overload and pulmonary hypertension by repairing the mitral valve. Despite a relatively high perioperative mortality rate, surviving patients benefitted from the operation, with improved clinical functional class and thus quality of life.

Clinical use of body surface potential mapping in cardiac arrhythmias.

Body surface potential maps have and certainly will have a very important role in the field of clinical arrhythmology, specifically for the localization of accessory pathways, for the detection of the origin of ventricular arrhythmias and for the identification of patients at risk of sudden death. In this particular setting, surface maps are certainly more useful than other more costly and sophisticated imaging techniques.

Improved mathematical model of the wear of the cup articular surface in hip joint prostheses and comparison with retrieved components.

This paper presents an analytical model of the cobalt-based alloy-ultra-high molecular weight polyethylene (UHMWPE) wear coupling. Based on a previous model in which the cup wear volume over a gait cycle (WG) was calculated under the simplifying assumption of an ideal rigid coupling, the current version proposes a more realistic wear simulation. All three components of the hip loading force were considered for the contact pressure calculation and all three components of the hip motion were taken into account for the sliding distance calculation. The contact pressure distribution was calculated on the basis of the Hertzian theory for the elastic contact of two bodies with non-conforming geometrical shapes. The wear factor was taken from hip simulator wear tests. The calculated WG is 67 x 10(-6) mm3 for a standard reference patient. The parametric model simulations show that WG increases linearly with the patient weight, femoral head diameter and surface roughness. It increases non-linearly to a maximum and decreases to an asymptotic value with increasing cup/head clearance and with cup isotropic elastic modulus. The cup orientation in the pelvis affects only slightly the total amount of WG whereas it is the dominant factor affecting the shape of the wear distribution. The iso-wear maps show paracentral patterns at low cup inclination angles and marginal patterns at higher inclination angles. The maximum wear depth is supero-posterior when the cup is in neutral alignment and supero-anterior at increasing anteversion angles. Complex patterns with a combination of paracentral and marginal wear were obtained at specific clearance values and cup orientations. The results of the simulations are discussed in relation to the wear distribution measured on the articular surface of 12 UHMWPE components retrieved from failed hip joint prostheses, after a period of in situ functioning.

Mass spectrometry and NMR analysis of ligand binding by human liver fatty acid binding protein.

Human liver fatty acid binding protein (hL-FABP) is the most abundant cytosolic protein in the liver. This protein plays important roles associated to partitioning of fatty acids (FAs) to specific metabolic pathways, nuclear signaling and protection against oxidative damage. The protein displays promiscuous binding properties and can bind two internal ligands, unlike FABPs from other tissues. Different topologies for the ligand located in the more accessible site have been reported, with either a 'head-in' or 'head-out' orientation of the carboxylate end. Electrospray-ionization mass spectrometry and nuclear magnetic resonance titrations are employed here in order to investigate in further detail the binding properties of this system, the equilibria established in solution and the pH dependence of the complexes. The results are consistent with two binding sites with different affinity and a unique head-out topology for the second molecule of either ligand. Competition experiments indicate a higher affinity for oleic acid relative to palmitic acid at each binding site.

Functional ischemic mitral regurgitation in anterior ventricular remodeling: results of surgical ventricular restoration with and without mitral repair.

Ischemic functional mitral regurgitation following ischemic cardiomyopathy is a secondary phenomenon to ventricular dilation, and therapeutic approaches to this complication are not uniform. Solutions to improve mitral function include either mitral repair or observing the effects of coronary revascularization and/or ventricular rebuilding during surgical ventricular restoration (SVR). The present study of 108 patients (comprising 18% of our 588 SVR population) reports the effects of mitral repair following SVR and CABG by comparing geometric, functional, hemodynamic and outcome changes to SVR patients without mitral repair. The degree of mitral regurgitation went from 2.9 +/- 1.2 before to 0.7 +/- 0.7 after SVR and mitral repair. SVR improved EF from 29 +/- 7% to 34 +/- 10% p 0.001; reduced end diastolic volume from 243 +/- 74 to 163 +/- 53 ml and end systolic volume from 170 +/- 63 to 107 +/- 41 ml, p 0.000. Ventricular size and shape geometric measurements improved in all patients, either with and without mitral repair. SVR improved tenting and papillary muscle width between muscle heads in all patients, but alterations in mitral annular size improved only following mitral repair. Preoperative mitral regurgitation occurred in patients with larger ventricular volume and lower ejection fraction and was an independent predictor of operative mortality risk.

Mesoglycan in treatment of patients with cerebral ischemia: effects on hemorheologic and hematochemical parameters.

The present study evaluates the hematochemical and hemorheologic effects of mesoglycan, a preparation of natural glycosaminoglycans, administered by the intramuscular route to patients with a recent episode of cerebral ischemia. A total of twenty patients (13 males and 7 females), between the ages of 45 and 75, under observation for a cerebral ischemic episode occurring at least 2 months prior to enrollment, were treated with intramuscular mesoglycan (30 mg, twice daily), for 15 days. Blood samples were taken prior to and at the end of treatment to measure the investigated parameters. Following mesoglycan treatment we observed a statistically significant decrease in fibrinogen plasma concentration, total cholesterol and triglycerides, while HDL cholesterol was found to increase. In addition, erythrocytes filterability improved at the end of treatment. No changes were observed in coagulation parameters such as prothrombin time, partial thromboplastin time, or antithrombin III. The results of the present study demonstrate that a 15-days treatment of intramuscular mesoglycan in patients recovering from a cerebral ischemic episode produces significant changes in fibrinogen and lipid plasma levels with no apparent anticoagulant effect.