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MiR-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.

Dermal exposure to Aluminium nanoparticles (AlNPs) can occur in occupationally- and non occupationally exposed- population, due to the use of Al salts-based antiperspirants. No AlNPs transdermal permeation data exists. Our study investigated in vitro the permeation of 30–60 nm Al2O3NPs dispersed in synthetic sweat (20 g/L) using excised human skin on Franz cells. Experiments were performed using intact (experiment 1) and needle-abraded skin (experiment 2). After 24 h traces of Al were detectable in receiving solution of exposed cells (35.0 ± 6.0 ng/cm2 for intact and 88.5 ± 34.2 ng/cm2 for damaged skin, mean and SD) and in blank cells (36.3 ± 7.0 ng/cm2), without statistical significance (p = 0.08, Mann-Whitney test). The average amount of Al into intact and damaged skin samples was 3.96 ± 0.20 μg/cm2 for intact and 4.36 ± 0.47 μg/cm2 for damaged skin (p = 0.08). Al content was similar in epidermal and dermal layers of intact and damaged skin (1.95 ± 0.13 μg/cm2 and 2.31 ± 0.12 μg/cm2 epidermal, 2.01 ± 0.25 μg/cm2 and 2.05 ± 0.35 μg/cm2 dermal). Al is a trace element in human body and the amount found in receiving solutions could be due as background impurity. This data suggest a reassuring transdermal permeation profile for Al2O3NPs.

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 0.29μg/cm2) and, to a lesser extent in dermis (up to 0.11μg/cm2). Further studies are required to evaluate the potential effects of long-term exposure to Ce.

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MnFe2O4 nanoparticles (NPs) are commonly produced in some occupational settings and may reach high concentration in activities such as arc-welding or ferroalloy metallurgy. Manganese is an essential cofactor in enzyme activities but it has been demonstrated that long-term exposure to excessive levels can lead to “manganism”, a neurodegenerative disease resembling Parkinson features. Inhaled NPs deposit partially in pharynx and nasopharynx and may reach the central nervous system through the olfactory nerve, which is completely enveloped by the meningeal membranes throughout its course from the nasal cavity to the olfactory bulb or through the trigeminal nerves. This study investigated in vitro the transmeningeal absorption of 50 nm MnFe2O4NPs, using excised porcine meninges mounted on Franz diffusion cells. We tested two donor solutions: the first containing MnFe2O4NPs (2.0 g/L) and the second obtained by the ultrafiltration of the first one, in order to test only the NPs water soluble fraction. Each experiment was carried separately for 4 h. Results showed that no Mn flux permeation through the meninges occurred, since only trace of the metal was found in receivers solutions of cells exposed to MnFeNPs (5.5 ± 2.2 ng/cm2), ultrafiltered solution (3.5 ± 1.5 ng/cm2) and blank cells. (2.1 ± 0.6 ng/cm2) (mean and SE). Differences did not reach the statistical significance. Our study shows – for the first time - that MnFe2O4NPs penetrate the meningeal membrane in a negligible amount, thus making unlikely the hypothesis of a transcellular and paracellular absorption through the olfactory nerve but not excluding the hypothesis of an active intraneuronal absorption.

We herein report an unusual case of a 40-year-old woman presenting to the emergency department with acute-onset tetraparesis due to inhalation of chemical solvents containing n-hexane. The clinical picture, a mild albumin-cytologic dissociation and the demyelinating features on nerve conduction study initially mimicked the presentation of Guillain-Barré syndrome (GBS), but the patient failed to respond to intravenous immunoglobulin treatment and plasma exchange. Diagnosis of hexane-induced neuropathy was then confirmed by means of sural nerve biopsy, showing axonal enlargement with secondary retraction and thinning of the myelin sheath.

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 ± 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 ± 2.0 vs 0.032 ± 0.010 μg cm(-2), p = 0.006) at 24 h. Total Ni amount into the skin was 29.2 ± 11.2 μg cm(-2) in damaged skin and 9.67 ± 2.70 μg 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.

Silver nanoparticles (AgNPs) can come in contact with human oral mucosa due to their wide use in food industry and hygiene devices. We evaluate transmucosal absorption of 19 nm AgNPs using excised porcine buccal mucosa applied on Franz diffusion cells. Two donor solutions were used: one containing AgNPs (0.5 g/L) and one derived from the ultrafiltration of the former and containing only Ag in its soluble form. Experiments were carried out separately for 4 h. Silver flux permeation was demonstrated through oral mucosa, showing similar values for AgNPs (6.8±4.5 ng cm(-2) h(-1)) and Ag ions (5.2±4.3 ng cm(-2) h(-1)). Our study demonstrates that silver can permeate the oromucosal barrier and that absorption is substantially due to Ag ions, since no permeation difference was found using the two solutions. Mucosal absorption has to be considered in further risk assessment studies.

It seems evident from a large number of studies that there is a positive relationship between exposure to whole body vibration (WBV) and the occurrence of low back pain. There are existing standards for evaluating the human exposure to WBV, which are based on other factors than the effect of musculoskeletal disorders. Several national and international standards also exist for evaluating human exposure to WBV. The exposure limit values or health guidance caution zones included in some of these standards are not or only to a limited extent based on systematic epidemiological investigations. It has not yet been possible to establish a clear exposure-response relationship. There are many confounding or contributing factors which influence the hazards to workers caused by exposure to WBV. Reliable methods for the detection and prevention of injury due to vibration exposure at work, alone or in combination with other risk factors, need to be implemented. The aim of this paper was to design a protocol and a questionnaire for conducting collaborative studies of WBV and musculoskeletal back disorders. The protocol will be tested in a pilot study before it will be used in multi-center studies. (C) 1998 Academic Press

The aim of this paper is to update the information on the epidemiologic evidence of the adverse health effects of whole-body vibration (WBV) on the spinal system by means of a review of the epidemiologic studies published between 1986 and 1996. In a systematic search of epidemiologic studies of low back pain (LBP) disorders and occupations with exposure to WBV, 37 articles were retrieved. The quality of each study was evaluated according to criteria concerning the assessment of vibration exposure, assessment of health effects, and methodology. The epidemiologic studies reaching an adequate score on each of the above mentioned criteria, were included in the final review. A meta-analysis was also conducted in order to combine the results of independent epidemiologic studies. After applying the selection criteria, 16 articles reporting the occurrence of LBP disorders in 19 WBV-exposed occupational groups, reached a sufficient score. The study design was cross-sectional for 13 occupational groups, longitudinal for 5 groups and of case-control type for one group. The main reasons for the exclusion of studies were insufficient quantitative information on WBV exposure and the lack of control groups. The findings of the selected studies and the results of the meta-analysis of both cross-sectional and cohort studies showed that occupational exposure to WBV is associated with an increased risk of LBP, sciatic pain, and degenerative changes in the spinal system, including lumbar intervertebral disc disorders. Owing to the cross-sectional design of the majority of the reviewed studies, this epidemiologic evidence is not sufficient to outline a clear exposure–response relationship between WBV exposure and LBP disorders. Upon comparing the epidemiological studies included in this review with those conducted before 1986, it is concluded that research design and the quality of exposure and health effect data in the field of WBV have improved in the last decade.

The authors report the first results of a global survey on the working conditions in the forests of the Italian Alps, where the mechanization of the operations is limited, owing to the difficult geomorphological conditions. First, an organizational analysis was performed in all the phases of forest work by using the method of organizational congruences. The physiological cost of each task was evaluated by measuring oxygen consumption, lung ventilation during work, and the heart rate through 24-hour continuous dynamic electrocardiograph recording. The postural load on the lumbar disks for the main logging tasks was evaluated by means of a biomechanical analysis that estimated the compressive force applied to disk L3 in different positions. The vibrations transmitted to the worker's hand/arm system during the cutting activities were also measured. The results of the analysis suggest that potentially hazardous situations can be reduced by training operators in safer work practices and that the work organization must be improved since most tasks are physically too demanding, from both the metabolic and the cardiac point of view. The postures habitually assumed by workers during cutting exert a load on intervertebral disks that is much higher than if they assumed an ergonomically correct position. The health risk from vibrations requires a careful control of both the working conditions and the worker's state of health.

The 2nd International Conference on Whole-Body Vibration Injuries, held in Siena (Italy), 7-9 November 2000, was organized by the Department of Prevention of the Local Health Unit 7 (AUSL 7) of Siena, in co-operation with the National Institute of Occupational Safety and Prevention (ISPESL) of Rome (Italy) and the University of Siena (Italy). The conference was sponsored by the European Commission under the BIOMED 2 Concerted Action BMH4-CT98-3291 (Vibration Injury Network). The conference took a similar form to the 1st International Conference on Whole-Body Vibration Injuries held at the Institute of Sound and Vibration Research, University of Southampton, England, 15-17 September 1997 (see Journal of Sound and Vibration 215, 1998). The vibration experienced by some vehicle and machine operators has long been suspected to be a cause of injuries. There is epidemiological evidence that occupational exposure to whole-body vibration is associated with an increased risk of low back pain, sciatic pain, and degenerative changes in the spinal system. There is, however, not yet sufficient data to outline a clear exposure-response relationship between whole-body vibration exposures and low back pain disorders. There are guides, standards and proposed legislation intended to protect workers from excessive exposure to whole-body vibration and mechanical shock. Models have been developed to predict forces in the spine associated with vibration and shock. Biodynamic models have been developed to estimate risks of injury and optimize environments so as to minimize risks. This conference provided a unique opportunity to exchange information on the potential for injury from whole-body vibration and mechanical shock, to increase understanding of the mechanisms of injury, to improve methods of investigating the effects of whole-body vibration and shock, and to disseminate understanding by means of preventing injury. Eighty persons participated in the conference from 16 countries: Brazil, Canada, Denmark, Greece, Finland, France, Germany, Italy, Japan, Poland, Sweden, The Netherlands, United Kingdom, Ukraine, United States of America, Yugoslavia. Researchers from various disciplines - biomechanics, physics, physiology, engineering and medicine - exchanged their ideas with respect to the state-of-the-art, the main criticisms of experimental and epidemiological data, and the future directions of research. The main topics of the papers presented at the conference involved: epidemiology, physiological measurements and pathological investigations, biodynamic measurements, models and analogues, measurement and evaluation of exposures, seating dynamics, guidelines, standards, and other preventative measures, compensation and legal implications. Thirty-four papers were presented at the conference. Following independent review, 18 of the papers have been accepted for publication in this issue of the Journal of Sound and Vibration. In addition to the benefits accruing to areas of biodynamics, modelling, clinical and epidemiological research, the advances in knowledge promoted by the papers have potentially important socio-economic implications. Such benefits were evident in a special session of the conference dedicated to preventative measures and the promotion of the transfer of knowledge from the laboratory to the field. Some of the results from work packages of the EU research project BIOMED 2 "Vibration Injury Network" identified preventative measures, including guidelines for whole-body vibration health surveillance, a survey of technical preventative measures to reduce whole-body vibration effects when designing mobile machinery, criteria for the recognition of whole-body vibration injury as an occupational disease, and a whole-body vibration database on the Internet. The main effort of this conference was to summarize the current state of knowledge in the field of whole-body vibration injuries and identify practical implications for risk prevention. The results of the conference confirmed that epidemiological data providing direct information on exposure-response relationships for spinal disorders induced by whole-body vibration are still limited. For this reason, emphasis was placed on the implications from experimental studies and clinical observations, the development of computational biomechanical models, and on research strategies to improve knowledge in the future. Together, this approach should provide a framework to facilitate the development of future guidelines and improve standardization of the assessment of the risks of whole-body vibration at the workplace and develop vibration-specific preventative measures.