Withdrawal of active treatments in terminally ill heart failure patients.

INTRODUCTION: Heart failure (HF) constitutes a growing public health problem in aging societies: when pharmacological therapies fail, HF can be sustained intensively if patients are eligible for either orthotopic heart transplantation (OHT) or mechanical ventricular assistance, otherwise additional treatments could be inappropriate. In December 2017 Italian Legislator brought in the provisions regarding the end-of-life choices, including indications for withdrawing and withholding life-sustaining therapies. The aim of our study was to provide an overview of the daily practice of our center with regard to terminally ill HF patients. METHODS AND RESULTS: In April 2019 the 7 intensivist cardiologists and 21 nurses of a tertiary ICCU were asked in, to complete a questionnaire relating to a hypothetical terminally ill HF patient for whom the decision to withdraw active treatment had been made. To assess current practice, we also identified patients who died in the previous 12 months. Out of 29 deceased patients, 18 were identified as terminally ill HF, with no indications for therapy upgrading. We observed a striking disparity between belief and practice. CONCLUSIONS: Our survey showed that the care of terminally ill HF patients in our ICCU was characterized by aggressive use of medical therapy and invasive technology. The wide disparity between belief and practice could be in part a consequence of lack of professional training, with regard to law, ethics and communication techniques.

Phase dependent encapsulation and release profile of ZIF-based biocomposites.

Biocomposites composed of Zeolitic Imidazolate Frameworks (ZIFs) are generating significant interest due to their facile synthesis, and capacity to protect proteins from harsh environments. Here we systematically varied the composition (i.e. relative amounts of ligand (2-methylimidazole), metal precursor (Zn(OAc)2·2H2O), and protein) and post synthetic treatments (i.e. washes with water or water/ethanol) to prepare a series of protein@ZIF biocomposites. These data were used to construct two ternary phase diagrams that showed the synthesis conditions employed gave rise to five different phases including, for the first time, biocomposites based on ZIF-CO3-1. We examined the influence of the different phases on two properties relevant to drug delivery applications: encapsulation efficiency and release profile. The encapsulation efficiencies of bovine serum albumin and insulin were phase dependent and ranged from 75% to 100%. In addition, release profiles showed that 100% protein release varied between 40 and 300 minutes depending on the phase. This study provides a detailed compositional map for the targeted preparation of ZIF-based biocomposites of specific phases and a tool for the straightforward analysis of the crystalline phases of ZIF based materials (web application named "ZIF phase analysis"). These data will facilitate the progress of ZIF bio-composites in the fields of biomedicine and biotechnology.

Influence of age and physical exercise on sirtuin activity in humans.

Sirtuins are NAD+-dependent lysine deacetylases. Sirtuins acquired worldwide attention because of their ability to increase yeast, flies, worms and mice lifespan. Recently, this assumption has been challenged. However, their beneficial role on the quality of ageing is widely accepted. In this work we aimed to study how and if sirtuins expression and activity levels varies in function of age and, in the case of young subjects, of exercise. Fifteen blood donors of different ages and fifteen athletes of the Italian rowing male team were enrolled and peripheral blood mononuclear cells (PBMCs) isolated from blood samples. Our results show that sirtuins deacetylases activity measured in PBMCs increases from 18 to 40 years of age and then decreases during the following 20 years. Moreover, physical exercise in professional athletes can upregulate sirtuin activity. Thus, for the first time in humans, we demonstrate that sirtuin activity is a function of age and can be altered through physical exercise.

SIRT3 protects from hypoxia and staurosporine-mediated cell death by maintaining mitochondrial membrane potential and intracellular pH.

Mitochondrial sirtuin 3 (SIRT3) mediates cellular resistance toward various forms of stress. Here, we show that in mammalian cells subjected to hypoxia and staurosporine treatment SIRT3 prevents loss of mitochondrial membrane potential (ΔΨ(mt)), intracellular acidification and reactive oxygen species accumulation. Our results indicate that: (i) SIRT3 inhibits mitochondrial permeability transition and loss of membrane potential by preventing HKII binding to the mitochondria, (ii) SIRT3 increases catalytic activity of the mitochondrial carbonic anhydrase VB, thereby preventing intracellular acidification, Bax activation and apoptotic cell death. In conclusion we propose that, in mammalian cells, SIRT3 has a central role in connecting changes in ΔΨ(mt), intracellular pH and mitochondrial-regulated apoptotic pathways.

Efficacy of oleuropein against UVB irradiation: preliminary evaluation.

Oleuropein, a phenolic compound derived from olive leaves and oil, is known to possess several biological properties, many of which may be attributed to its antioxidant and free radical-scavenging activities. Nevertheless, up to now, the cosmetic activity of this molecule has not been extensively investigated. The aim of this work was to evaluate the cosmetic properties of oleuropein against UVB-induced erythema. To this end, an emulsion and an emulgel containing oleuropein were prepared, applied and evaluated on healthy volunteers who had undergone UVB irradiation to investigate its protective and/or lenitive activity. Protective effect was assayed by application of topical preparations before irradiation and lenitive effect was evaluated after erythema induction. Vitamin E was used as the reference compound. Our study was carried out by using noninvasive techniques to assess specific skin parameters: barrier function, skin colour and microcirculation. Results clearly showed that oleuropein formulations highlighted lenitive efficacy by reducing erythema, transepidermal water loss and blood flow of about 22%, 35% and 30% respectively. The study allowed us to point out the lenitive property of oleuropein, opening the way to further trials to deepen our specific knowledge about this natural molecule, which could be used in association with other active ingredients in cosmetics to repair UV damages.

[Evaluation of the bactericidal activity of a disinfectant containing sodium hypochlorite (Amiclor)]. / Valutazione dell'attività battericida di un disinfettante a base di ipoclorito di sodio (Amiclor).

We evaluated the stability and the bactericidal activity of a disinfectant containing sodium hypochlorite (Amiclor), which associates the buffer effect of the system sodium carbonate/sodium tetraborate to the stabilizing action of sodium chloride. The stability was determined evaluating the trend of the active chlorine title in various conservation conditions and comparing it with a product having only sodium chloride as stabilizing component. The bactericidal activity, instead, was evaluated by suspension and surface tests against Escherichia coli (ATCC 10536) and in relation to several variables, as product concentration, contact time, presence of interfering substances and water hardness. From the obtained data it is possible to affirm that Amiclor owns a greater stability as regards the traditional products stabilized only with sodium chloride. The activity tests have pointed out that the practical conditions affect the choice of the combination "product concentration/contact time" necessary to obtain an effective bactericidal activity. The activity of Amiclor is conditioned by the presence of proteins in the mixture or on the surface of reaction. This influence is not very clear in clean conditions while it considerably increases in dirty conditions. A decrease of bactericidal activity was observed when the product was diluted in hard water, mainly for contact times of 5 minutes or low product concentrations.

Calcium ions and 1-palmitoyl carnitine reduce erythrocyte electrophoretic mobility: test of a surface charge hypothesis.

In ventricular muscle, 1-palmitoyl carnitine (1-PC) acted like calcium ions to shift the voltage-dependent inactivation of excitatory ion currents to less negative potentials. We proposed that 1-PC affected ion current kinetics by reducing surface negative charge. This hypothesis was tested in cell electrophoresis experiments where the electrophoretic mobility (EPM) of erythrocytes was measured in the absence and presence of test ligands. Calcium (0.18 to 3.6 mM) or 1-PC (10(-7) to 10(-6) M) reduced erythrocyte EPM in a concentration-dependent manner; the maximum reduction of EPM by either ligand was approximately 40%. In the presence of calcium, 1-PC produced a smaller decrement of EPM as expected from an occlusive interaction. Treatment of erythrocytes to remove sialic acids not only predictably reduced EPM but also diminished the ability of 1-PC and calcium to do so. These results indicate that the surface negative charge of sialic acid carboxyl groups is an important determinant both of erythrocyte EPM and of erythrocyte interaction with either 1-PC or calcium. The findings are consistent with the surface charge hypothesis for 1-PC action. We propose that 1-PC is not a neutral molecule at the cell surface but is able to neutralize surface negative charge by electrostatic interaction between the sialic acid carboxyl groups and the 1-PC quaternary ammonium moiety on the one hand and between the 1-PC carboxyl group and counterions near the membrane surface.