In vitro dermal penetration of nickel nanoparticles.

Nickel nanoparticles (NiNPs) represent a new type of occupational exposure because, due to the small size/high surface, they can release more Ni ions compared to bulk material. It has been reported a case of a worker who developed sensitization while handling nickel nanopowder without precautions. Therefore there is the need to assess whether the skin absorption of NiNPs is higher compared to bulk nickel. Two independent in vitro experiments were performed using Franz diffusion cells. Eight cells for each experiment were fitted using intact and needle-abraded human skin. The donor phase was a suspension of NiNPs with mean size of 77.7 \ub1 24.1 nm in synthetic sweat. Ni permeated both types of skin, reaching higher levels up to two orders of magnitude in the damaged skin compared to intact skin (5.2 \ub1 2.0 vs 0.032 \ub1 0.010 \u3bcg cm(-2), p = 0.006) at 24 h. Total Ni amount into the skin was 29.2 \ub1 11.2 \u3bcg cm(-2) in damaged skin and 9.67 \ub1 2.70 \u3bcg cm(-2) in intact skin (mean and SD, p = 0.006). Skin abrasions lead to doubling the Ni amount in the epidermis and to an increase of ten times in the dermis. This study demonstrated that NiNPs applied on skin surface cause an increase of nickel content into the skin and a significant permeation flux through the skin, higher when a damaged skin protocol was used. Preventive measures are needed when NiNPs are produced and used due to their higher potential to enter in our body compared to bulk nickel

Transdermal permeation of inorganic cerium salts in intact human skin

The stratum corneum protects the body against external agents, such as metals, chemicals, and toxics. Although it is considered poorly permeable to them, comprising the major barrier to the permeation of such substances, it may become a relevant gate of entry for such molecules. Cerium (Ce) is a lanthanide that is widely used in catalytic, energy, biological and medicinal applications, owing to its intrinsic structural and unique redox properties. Cerium salts used to produce cerium oxide (CeO2) nanostructures can potentially come into contact with the skin and be absorbed following dermal exposure. The objective of this study was to investigate the percutaneous absorption of three inorganic Ce salts: cerium (III) chloride (CeCl3); cerium (III) nitrate (Ce(NO3)3) and ammonium cerium (IV) nitrate (Ce(NH4)2(NO3)6), which are commonly adopted for the synthesis of CeO2 using in vitro - ex vivo technique in Franz diffusion cells. The present work shows that Ce salts cannot permeate intact human skin, but they can penetrate significantly in the epidermis (up to 0.29 μg/cm2) and, to a lesser extent in dermis (up to 0.11 μg/cm2). Further studies are required to evaluate the potential effects of long-term exposure to Ce

In vitro permeability of silver nanoparticles through porcine oromucosal membrane

Silver nanoparticles (AgNPs) can come in contact with human oral mucosa due to their wide use infood industry and hygiene devices. We evaluate transmucosal absorption of 19 nm AgNPs using excisedporcine buccal mucosa applied on Franz diffusion cells. Two donor solutions were used: one containingAgNPs (0.5 g/L) and one derived from the ultrafiltration of the former and containing only Ag in its solubleform. Experiments were carried out separately for 4 h. Silver flux permeation was demonstrated throughoral mucosa, showing similar values for AgNPs (6.8 \ub1 4.5 ng cm 122h 121) and Ag ions (5.2 \ub1 4.3 ng cm 122h 121).Our study demonstrates that silver can permeate the oromucosal barrier and that absorption is sub-stantially due to Ag ions, since no permeation difference was found using the two solutions. Mucosalabsorption has to be considered in further risk assessment studies

Palladium nanoparticles exposure: Evaluation of permeation through damaged and intact human skin.

8noThe intensified use of palladium nanoparticles (PdNPs) in many chemical reactions, jewellery, electronic devices, in car catalytic converters and in biomedical applications lead to a significant increase in palladium exposure. Pd can cause allergic contact dermatitis when in contact with the skin. However, there is still a lack of toxicological data related to nano-structured palladium and information on human cutaneous absorption. In fact, PdNPs, can be absorbed through the skin in higher amounts than bulk Pd because NPs can release more ions. In our study, we evaluated the absorption of PdNPs, with a size of 10.7 ± 2.8 nm, using intact and damaged human skin in Franz cells. 0.60 mg cm-2 of PdNPs were applied on skin surface for 24 h. Pd concentrations in the receiving solutions at the end of experiments were 0.098 ± 0.067 μg cm-2 and 1.06 ± 0.44 μg cm-2 in intact skin and damaged skin, respectively. Pd flux permeation after 24 h was 0.005 ± 0.003 μg cm-2 h-1 and 0.057 ± 0.030 μg cm-2 h-1 and lag time 4.8 ± 1.7 and 4.2 ± 3.6 h, for intact and damaged skin respectively. This study indicates that Pd can penetrate human skin.partially_openembargoed_20180429Larese Filon, F; Crosera, M; Mauro, M; Baracchini, E; Bovenzi, M; Montini, T; Fornasiero, P; Adami, G.LARESE FILON, Francesca; Crosera, Matteo; Mauro, Marcella; Baracchini, Elena; Bovenzi, Massimo; Montini, Tiziano; Fornasiero, Paolo; Adami, Gianpier

Pilot study on in vitro silver nanoparticles permeation through meningeal membrane

Silver nanoparticles (AgNPs) are commonly used in antiseptic sprays and mist and can easily come in contact with the mucosa of the upper airways. The intranasal pathway represents the only direct connection between the external environment and the brain structures, which traditionally are considered well protected. Much is known regarding drugs absorption through this route, but toxicological knowledge is scant. The olfactory bundles are surrounded by meningeal sheets in their course from the nasal mucosa to the olfactory bulb. This study investigated in vitro the transmeningeal absorption of 19 nmAgNPs, using excised porcine meninges mounted on Franz diffusion cells. We used two donor solutions: the first containing AgNPs (0.5 g/L) and the second containing only the water-soluble silver species derived from the ultrafiltration of the first one. Each experiment was carried separately for 2 hours. Results showed silver flux permeation through the meninges, with similar values in both experiments (0.78 \ub1 0.71 ng cm-2 h-1 and 0.73 \ub1 0.43 ng cm-2 h-1, for AgNPs and Ag ions respectively, mean and SD). Our study demonstrate that the meningeal barrier is permeable to silver and silver ions, when is applied in the nanoparticles form. This could lead to neurotoxic and neurodegenerative effects, which are now emerging in the scientific literature. Metal nanoparticles are commonly encountered in working scenarios, but their behavior in physiological media is different. Therefore the toxicological potential of metal NPs is heterogeneous and requires further efforts to be assessed on a case by case basis

Somatic disorders and antidepressant use in suicides: A population-based study from the Friuli Venezia Giulia region, Italy, 2003-2013

Background: Many somatic disorders are complicated by depression and increase the risk of suicide. Little is known about whether antidepressants might reduce the suicidal risk in patients with somatic disorders. Methods: Data on diagnoses and antidepressant prescriptions were derived from the Social and Health Information System of the Friuli Venezia Giulia Region. Cases were all suicides that occurred in the region during the years 2003\u20132013 and were sex- and age-matched to controls from the general population. Conditional logistic regression analysis was used to assess the association between suicide and somatic disorders. Results: The suicide rate in Friuli Venezia Giulia decreased from 11.3 to 10.7 per 100,000 inhabitants during the years 2003\u20132013, however patients with somatic disorder had a three times increased risk of suicide. Elderly somatic patients' suicide risk was twice as high as younger patients. The risk increased from 2.6 to 9.8 times as the number of comorbid disorders increased from 1 to 4 and over. Although no significant risk of suicide in patients with somatic disorders was found when patients were adherent to antidepressants, only 11.5% of the suicides was adherent in the year prior to death. Conclusions: Medical illnesses and underlying depressive symptoms may have a synergy effect on the risk of suicide, particularly in older patients and in patients with multiple morbidities. Since medically ill subjects adherent to antidepressants did not showa significant risk of suicide, early identification and adequate treatment of depression in somatic patients should be considered in order to prevent suicide

Parkinson's disease motor progression in relation to the timing of REM sleep behavior disorder presentation: an exploratory retrospective study

REM sleep behavior disorder (RBD) is a frequent non-motor symptom of parkinson's disease (PD), and the timing of its presentation might have a role in the underlying neurodegenerative process. Here, we aimed to define the potential impact of probable RBD (pRBD) on PD motor progression. we conducted a longitudinal retrospective study on 66 PD patients followed up at the university hospital of rome tor vergata. patients were divided into three groups: with post-motor pRBD (pRBD(post), n = 25), without pRBD (pRBD(wo), n = 20), and with pre-motor pRBD (pRBD(pre), n = 21). Hoehn and Yahr (H&Y) scores, unified PD rating scale (UPDRS) motor scores, and levodopa equivalent daily dose were collected at two follow-up visits conducted in a 5-year interval (T0 and T1). pRBD(post )patients had a greater rate of motor progression in terms of the H&Y scale compared to pRBD(pre) and pRBD(wo) patients, without the influence of anti-parkinsonian treatment. these preliminary findings suggest that the post-motor occurrence of pRBD can be associated with an acceleration in PD motor progression

Exosomal transfer of miR-126 promotes the anti-tumour response in malignant mesothelioma: Role of miR-126 in cancer-stroma communication

none11MiR-126 has been shown to suppress malignant mesothelioma (MM) by targeting cancer-related genes without inducing toxicity or histopathological changes. Exosomes provide the opportunity to deliver therapeutic cargo to cancer stroma. Here, a tumour stromal model composed of endothelial cells (HUVECs), fibroblasts (IMR-90 cells), non-malignant mesothelial cells (Met-5A cells) and MM cells (H28 and MM-B1 cells) was used. The cells were treated with exosomes from HUVECs carrying endogenous (exo-HUVEC) and enriched miR-126 (exo-HUVECmiR-126), and the uptake/turnover of exosomes; miR-126 distribution within the stroma; and effect of miR-126 on cell signalling, angiogenesis and cell proliferation were evaluated. Based on the sensitivity of MM cells to exo-HUVEC miR-126 treatment, miR-126 was distributed differently across stromal cells. The reduced miR-126 content in fibroblasts in favour of endothelial cells reduced angiogenesis and suppressed cell growth in an miR-126-sensitive environment. Conversely, the accumulation of miR-126 in fibroblasts and the reduced level of miR-126 in endothelial cells induced tube formation in an miR-126-resistant environment via VEGF/EGFL7 upregulation and IRS1-mediated cell proliferation. These findings suggest that transfer of miR-126 via HUVEC-derived exosomes represents a novel strategy to inhibit angiogenesis and cell growth in MM.noneMonaco, Federica; Gaetani, Simona; Alessandrini, Federica; Tagliabracci, Adriano; Bracci, Massimo; Valentino, Matteo; Neuzil, Jiri; Amati, Monica; Bovenzi, Massimo; Tomasetti, Marco; Santarelli, LoryMonaco, Federica; Gaetani, Simona; Alessandrini, Federica; Tagliabracci, Adriano; Bracci, Massimo; Valentino, Matteo; Neuzil, Jiri; Amati, Monica; Bovenzi, Massimo; Tomasetti, Marco; Santarelli, Lor

Percutaneous Treatment of Aortic Coarctation in Young Adult Supported by Novel Fusion Imaging Technology

Coarctation of the aorta (CoA) accounts for 6%–8% of all congenital heart disease (CHD), but it is the most commonly missed..

MiR-126 in intestinal-type sinonasal adenocarcinomas: exosomal transfer of MiR-126 promotes anti-tumour responses

Background: Intestinal-type sinonasal adenocarcinomas (ITACs) are aggressive malignancies related to wood dust and leather exposure. ITACs are generally associated with advanced stage at presentation due to the insidious growth pattern and non-specific symptoms. Therefore, biomarkers that can detect the switch from the benign disease to malignancy are needed. Essential for tumour growth, angiogenesis is an important step in tumour development and progression. This process is strictly regulated, and MiR-126 considered its master modulator. Methods: We have investigated MiR-126 levels in ITACs and compared them to benign sinonasal lesions, such as sinonasal-inverted papillomas (SIPs) and inflammatory polyps (NIPs). The tumour-suppressive functions of MiR-126 were also evaluated. Results: We found that MiR-126 can significantly distinguish malignancy from benign nasal forms. The low levels of MiR- 126 in ITACs point to its role in tumour progression. In this context, restoration of MiR-126 induced metabolic changes, and inhibited cell growth and the tumorigenic potential of MNSC cells. Conclusions: We report that MiR-126 delivered via exosomes from endothelial cells promotes anti-tumour responses. This paracrine transfer of MiRs may represent a new approach towards MiR-based therapy