Shear-promoted drug encapsulation into red blood cells: a CFD model and μ-PIV analysis

The present work focuses on the main parameters that influence shear-promoted encapsulation of drugs into erythrocytes. A CFD model was built to investigate the fluid dynamics of a suspension of particles flowing in a commercial micro channel. Micro Particle Image Velocimetry (μ-PIV) allowed to take into account for the real properties of the red blood cell (RBC), thus having a deeper understanding of the process. Coupling these results with an analytical diffusion model, suitable working conditions were defined for different values of haematocrit

Experimental support of the scaling rule for demographic stochasticity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73613/1/j.1461-0248.2006.00903.x.pd

A new bioavailable fenretinide formulation with antiproliferative, antimetabolic, and cytotoxic effects on solid tumors

Fenretinide is a synthetic retinoid characterized by anticancer activity in preclinical models and favorable toxicological profile, but also by a low bioavailability that hindered its clinical efficacy in former clinical trials. We developed a new formulation of fenretinide complexed with 2-hydroxypropyl-beta-cyclodextrin (nanofenretinide) characterized by an increased bioavailability and therapeutic efficacy. Nanofenretinide was active in cell lines derived from multiple solid tumors, in primary spheroid cultures and in xenografts of lung and colorectal cancer, where it inhibited tumor growth independently from the mutational status of tumor cells. A global profiling of pathways activated by nanofenretinide was performed by reverse-phase proteomic arrays and lipid analysis, revealing widespread repression of the mTOR pathway, activation of apoptotic, autophagic and DNA damage signals and massive production of dihydroceramide, a bioactive lipid with pleiotropic effects on several biological processes. In cells that survived nanofenretinide treatment there was a decrease of factors involved in cell cycle progression and an increase in the levels of p16 and phosphorylated p38 MAPK with consequent block in G0 and early G1. The capacity of nanofenretinide to induce cancer cell death and quiescence, together with its elevated bioavailability and broad antitumor activity indicate its potential use in cancer treatment and chemoprevention

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Ossigenazione del sangue in circuiti di circolazione extracorporea

Tesi di Dottorato di Ricerc

The use of liquid perfluorocarbons for neonatal lung ventilation

Over the last years, physiological studies have proved that ventilation with a oxygenated liquid perfluorocarbon (PFC) provides effective gas exchange and acid base balance and improves lung function and recovery Low surface tension and high respiratory gas solubility enable adequate oxygenation and carbon dioxide removal at low insufflation pressure. The elimination of air-liquid interfacial surface tension has recently suggested the adoption of total liquid PFC ventilation as an investigational therapy for severe respiratory distress in human infants. This work is aimed to determine the optimal volumes of PFC to be delivered, the frequency of the ventilatory cycle, the oxygen flow rate and the best circuit set up for neonatal application. The optimisation was obtained through the implementation of a simulation mathematical model of oxygen diffusion in a PFC-ventilated lung and of gas exchange between alveolar environment and pulmonary blood flow. The results show that total liquid ventilation is a valid alternative to traditional gas ventilation, particularly when immature neonates with insufficient or absent production of surfactant are concerned. </jats:p