Claudia Giliberti

Ultrasound well below the intensity threshold of cavitation can promote efficient uptake of small drug model molecules in fibroblast cells

Abstract Ultrasound (US) induced enhancement of plasma membrane permeability is a hugely promising tool for delivering exogenous vectors at the specific biological site in a safe and efficient way. In this respect, here we report effects of membrane permeability alteration on fibroblast-like cells undergoing very low-intensity of US. The change in permeability was pointed out in terms of high uptake efficiency of the fluoroprobe calcein, thus resembling internalization of small cell-impermeable model drugs, as measured by fluorescence microscopy and flow cytometry. Fluorescence evidences moreover suggests that the higher the time of exposure, the larger will be the size of molecules can be internalized. The uptake events were related to the cell viability and also with structural changes occurring at membrane level as revealed by infrared spectroscopy and preliminary membrane fluidity and atomic force microscopy (AFM) investigation. Thus, the question of whether the uptake of cell-impermeable molecules is consistent with the presence of disruptions on the cell membrane (sonopore formation) has been addressed. In this framework, our findings may constitute experimental evidence in support of sub-cavitation sonoporation models recently proposed, and they may also provide some hints towards the actual working condition of medical US dealing with the optimum risk to benefit therapeutic ratio.

Monitoring of people and workers exposure to the electric, magnetic and electromagnetic fields in an Italian national cancer Institute

BackgroundThe paper reports the electric, magnetic and electromagnetic fields (emf) measurements carried out in the Regina Elena National Cancer Institute (NCI). Several devices, used in diagnostics and in medical cures, can represent sources of emf for the workers and for the public subjected to the treatments. The aim is to evaluate their exposition, in order to assess the compliance with the law.MethodsThe investigations have been carried out in the departments of: intensive care, physiotherapy, MR presstherapy and in the surgical rooms. The measurements have been performed using broad band probes in the frequency ranges 5 Hz÷30 kHz and 100 kHz-3 GHz.ResultsThe variability of the magnetic induction (B(μT)) levels is between 0,05 μT and 80 μT. The statistical distribution shows that most of the measurements are in the range 0,05<B = 0,5 μT and the 89% of the B(μT) levels are within the 3 μT.ConclusionThe measurement of the emf levels in the NCI is recommended because of the presence of the oncological patients; their long stay near the equipments and their day-long exposure represent additional risk factors for which a prudent avoidance strategy have to de adopted.

Structural and permeability sensitivity of cells to low intensity ultrasound: Infrared and fluorescence evidence in vitro.

This work is focused on the in vitro study of the effects induced by medical ultrasound (US) in murine fibroblast cells (NIH-3T3) at a low-intensity of exposure (spatial peak temporal average intensity Ita<0.1Wcm(-2)). Conventional 1MHz and 3MHz US devices of therapeutic relevance were employed with varying intensity and exposure time parameters. In this framework, upon cells exposure to US, structural changes at the molecular level were evaluated by infrared spectroscopy; alterations in plasma membrane permeability were monitored in terms of uptake efficiency of small cell-impermeable model drug molecules, as measured by fluorescence microscopy and flow cytometry. The results were related to the cell viability and combined with the statistical PCA analysis, confirming that NIH-3T3 cells are sensitive to therapeutic US, mainly at 1MHz, with time-dependent increases in both efficiency of uptake, recovery of wild-type membrane permeability, and the size of molecules entering 3T3. On the contrary, the exposures from US equipment at 3MHz show uptakes comparable with untreated samples.

Potential genotoxic effects of low-intensity ultrasound on fibroblasts, evaluated with the cytokinesis-block micronucleus assay.

Although medical ultrasound offers compelling opportunities to improve therapy in principle, progress in the field has been limited because of an insufficient understanding of the potential genotoxic and cytotoxic effects of ultrasound on biological systems. This paper is mainly focused on an in vitro study of effects with respect to genotoxicity and viability induced by 1- and 3-MHz medical ultrasound in murine fibroblasts (NIH-3T3) at low-intensity exposure (spatial peak temporal average intensity Ita<0.1 W/cm(2)). The NIH-3T3 cells constitute a well-characterized in vitro cell model in which a genotoxic effect can be predicted by means of a reliable and precise murine cytokinesis-block micronucleus assay. A statistically significant increase in the incidence of micronuclei was observed in sonicated 3T3 cells. In particular, the effects were more evident at 1 MHz. Moreover, for each frequency investigated, the occurrence of micronuclei was comparatively more frequent with increasing time of exposure. The possible toxicological implications of the medical ultrasound employed herein deal with the existence of a window of exposure parameters (set well below the intensity of ultrasound cavitation) in which some genotoxic effects may occur without significant cytotoxicity. In this respect, they provide new insight toward the correct risk to benefit balancing of ultrasound-based treatments and for designing innovative therapeutic strategies.

Potential third-party radiation exposure from patients undergoing therapy with 131I for thyroid cancer or metastases.

AbstractThe purpose of this work is to evaluate the potential third-party radiation exposure from patients undergoing therapy with 131I for ablation of residual thyroid tumor or metastases, based in part on serial measurements of exposure rates. Exposure rate measurements were performed at 1 m and 5 cm from the surface of each treated patient until patient release. Dose estimates based on measured exposure rates were compared with those based on analytic point-source (PSM) and line-source (LSM) models. Effective doses D(∞) to travelers, co-workers and sleeping partners were estimated by using the standard gamma factor (&Ggr;) and the physical half-life or the values derived from measured data. Seven hundred ten patients were studied until the exposure at 1 m was below the constraints of 0.010 mSv. The 131I activities administered ranged from 1.85 to 11.0 GBq (median: 3.7 GBq), according to the therapeutic requirements. Based on the PSM and an experimental &Ggr;, the mean/maximum estimated D(∞) to sleeping partners, partners, travelers, and co-workers were 2.60/20.65, 0.32/2.53, 0.96/7.59, and 0.57/4.50 mSv, respectively. Using the LSM and an experimental &Ggr;, the D(∞) values were 2.41/19.15, 0.32/2.50, 0.83/6.62, and 0.57/4.42 mSv, respectively, while they were almost double using the theoretical &Ggr;. The results presented, based on measured data in a large cohort of 131I-treated thyroid cancer patients, will allow more accurate estimation of potential third-party D(∞) following patient release and thus may be used to better inform physicians and hospital staff on recommendations for patient release and post-release precautions following radioiodine therapies.

Genomic damage induced by 1‐MHz ultrasound in vitro

Genotoxic effects of therapeutic ultrasound are poorly documented, when compared with the wide use of this physical agent. The aim of this work was to investigate the clastogenic and aneugenic potential of 1 MHz ultrasound, employing intensities (200 and 300 mW/cm2) above the cavitational threshold, but in the range of those normally used in therapeutics. Both normal fibroblasts (AG01522) and tumoral cells (MCF‐7) were sonicated. While no effects on viability were noted, significant increases of CREST‐negative micronuclei (indicative of clastogenesis) and CREST‐positive micronuclei (indicative of aneuploidy) were detected. Clastogenesis was confirmed by increases of γ‐H2AX foci, while increases of spindle anomalies confirmed the induction of aneuploidy. Our results confirm previous works that showed ultrasound‐induced DNA breakage. Moreover, our experiments show that the known effect of ultrasound‐induced damage to microtubules is also able to damage the mitotic spindle and induce aneuploidy. On the overall, this work highlights the importance to further investigate the potential risks related to therapeutics US. Environ. Mol. Mutagen. 59:60–68, 2018.

When Being a Woman Represents a Major Risk of Commuting Accidents

Since 2010, National Institute for Insurance against Accidents at Work (INAIL) recognized commuting accidents as work injury. Commuting is the leading cause of death among Italian and immigrant women. Commuting disabilities have been studied from INAIL records within the last five years (2012–2016). Results show how women present more disabilities in commuting than men (53.2% vs 46.8% men, p < 0,001). Men show more disabilities due to commuting with vehicle (39.8% vs 36.8% women) while commuting without vehicle is more frequent among women (16.4% vs 7% men, p < 0,05) with more permanent disabilities and severe ones (20.4% vs 9% men, p < 0.001; severe 16.5% vs 7.2% men, p < 0,001). Skeleton-motor apparatus is the most affected among women (87.7% vs 80.7% men, p < 0.001) in all work injury disabilities. Lower limbs are the women body site mainly injured (40.4% women vs 38.6% men, p < 0.01) after upper limbs.

Analysis and evaluation of good practices in the design of internet sites dedicated to electromagnetic fields and health

Purpose – The purpose of this paper is to apply a dedicated checklist for the evaluation of good practice information in the design of Italian internet sites on electromagnetic fields (emf) and health.Design/methodology/approach – The “Guidelines on the collection, evaluation and dissemination of good practice information on the Internet” by European Occupational Safety and Health Agency (EU‐OSHA) and the criteria of effective health communication, by the American National Institute of Health (NIH), have been reoriented to the issue “emf and health”. In total, 100 Italian internet sites, provided by the search engine GoogleItalia, have been analysed.Findings – The results show how Italian official sources of information on “emf and health”, mainly affiliated to public institutions, apply good practice criteria in the design of internet sites, in terms of Identity card of the provider, quality of information, usability, interactivity and content of the sites.Practical implications – In recent years, the in...