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The post hoc analysis presented here aimed to address the influence of endogenous vitamin D in the immunological mechanism underlying effective mite allergoid immunotherapy (AIT). Previously, we have shown that in allergic children, after 12 months of this immunoactive treatment, functionally potentiated memory regulatory T cells are identified. Indeed, AIT is the only known treatment that is able to reshape the detrimental immune response against the allergen into a non-noxious one. Besides, VD is widely considered an immunoregulatory molecule that is endogenously produced and exogenously provided by foods and supplements that might interact with the AIT mechanism, thus affecting its outcome. Therefore, a post hoc analysis of the clinical and immunological data from three different cohorts of allergic patients was performed. One cohort (N = 70) was on a standard symptom-controlling pharmacological treatment, while the other two (N = 60 and N = 35) were treated with AIT for 12 months. In the first cohort, a lower mean endogenous VD level (

Superparamagnetic nanoparticles, exposed to an external variable magnetic field, undergo rapid excitation/relaxation. So-called soft magnets, typically iron-based, rapidly and completely relax when the magnetic field returns to zero. Instead, cobalt-based (CoB) hard magnets retain residual magnetization, a characteristic related with the procedure for nanoparticles (NPs) production. Many researchers are still attracted by the potential of CoB NPs for theranostics as multifaced signal probes for imaging, microrobots, enhanced thermo/radiation therapy, and drug release. Since iron oxide NPs are the only magnetic NPs approved for human use, they are of reference for analyzing the potential of the disregarded CoB NPs. In vitro observed toxicity of CoB NPs, largely attributable to cobalt ions and other chemical species released by dissolution, excluded them from further investigations in humans. Nevertheless, experimental evidences documenting the in vivo toxicity of engineered CoB NPs remain very few. The surface functionalization adds newer properties and could improve the biocompatibility of NPs, critical for the clinical exploitation. In our opinion, it would be worth to further exploit the potential of finely tunable properties of CoB NPs in in vivo systems in order to establish a systematic database of properties and effects suitable for human application.

To provide an update on the possible role of nanoparticles as sensitizing occupational agents and on the influence of nanoparticles-exposure on the appearance/exacerbation of occupational allergy.Recent case reports, epidemiological studies, and experimental investigations in cellular and animal models demonstrated the potential for nanomaterials to favor/interfere with occupational allergy. First data are emerging on the sensitizing potential of nanoparticles that can act as haptens linking to proteins, with a formation of a 'corona'. Nanoparticles with carrier protein become a complete antigen and induce specific immune response. Moreover, they act as adjuvant favoring sensitization to bound molecules. The disruption of the respiratory and skin barrier, the modulation of immune response toward Th1 or Th2 immune reaction and the interaction with immune effector cells (mast cells and eosinophil in particular) can explain the potential for nanoparticles to exacerbate pre-existing allergic conditions.the exposure to nanoparticles represents a possible risk for occupational allergy both in the respiratory tract and in the skin. A deeper knowledge on the role of nanomaterials in the etiology/development of the allergic disease will allow to implement risk assessment and preventive measures for nanosafety in the contest of technological expansion.

A new instrumental neutron activation analysis (INAA) for the simultaneous determination of titanium (TiO

Multiple myeloma (MM) is a hematological disease that is still not curable. The bone marrow milieu, with cellular and non-cellular elements, participate in the creation of a pro-tumoral environment enhancing growth and survival of MM plasma cells. Exosomes are vesicles oscillating in dimension between 50 nm and 100 nm in size that can be released by various cells and contribute to the pathogenesis and progression of MM. Exosomes enclose proteins, cytokines, lipids, microRNAs, long noncoding RNAs, and circular RNAs able to regulate interactions between MM plasma cells and adjacent cells. Through exosomes, mesenchymal stem cells confer chemoresistance to MM cells, while myeloma cells promote angiogenesis, influence immune response, cause bone lesions, and have an impact on the outcome of MM patients. In this review, we analyze the role played by exosomes in the progression of monoclonal gammopathies and the effects on the proliferation of neoplastic plasma cells, and discuss the possible employment of exosomes as potential targets for the treatment of MM patients.

Conventional chemotherapy has partial therapeutic effects against hematological malignancies and is correlated with serious side effects and great risk of relapse. Recently, immunotherapeutic drugs have provided encouraging results in the treatment of hematological malignancies. Several immunotherapeutic antibodies and cell therapeutics are in dynamic development such as immune checkpoint blockades and CAR-T treatment. However, numerous problems restrain the therapeutic effectiveness of tumor immunotherapy as an insufficient anti-tumor immune response, the interference of an immune-suppressive bone marrow, or tumoral milieu with the discharge of immunosuppressive components, access of myeloid-derived suppressor cells, monocyte intrusion, macrophage modifications, all factors facilitating the tumor to escape the anti-cancer immune response, finally reducing the efficiency of the immunotherapy. Nanotechnology can be employed to overcome each of these aspects, therefore having the possibility to successfully produce anti-cancer immune responses. Here, we review recent findings on the use of biomaterial-based nanoparticles in hematological malignancies immunotherapy. In the future, a deeper understanding of tumor immunology and of the implications of nanomedicine will allow nanoparticles to revolutionize tumor immunotherapy, and nanomedicine approaches will reveal their great potential for clinical translation.

Mast cells are abundant in the heart, among myocardial fibers, around coronary arteries, within arterial intima and intramural vessels, and in atherosclerotic plaques. Their mediators can be released during anaphylaxis and be responsible for acute coronary syndrome. This condition has been described as Kounis syndrome (KS). We report three cases of acute myocardial ischemia, which fulfill the definition for KS. In Cases 1 and 2, the association of intense chest pain with acute urticaria after an allergenic contact (wasp sting and betalactam antibiotic administration, respectively) was suspected to be an attack of angina related to an allergic reaction. No signs of an allergic reaction were observed in Case 3, but only the history of a wasp sting suggested its relationship to loss of consciousness and heart ischemia when hypersensitivity to venom was ascertained. These cases strongly recommend measurement of anaphylactic biomarkers, such as tryptase, during acute coronary syndromes to detect the possible involvement of an allergic reaction. Conversely, measurement of cardiac biomarkers during anaphylaxis, even without obvious signs of myocardial ischemia, might identify patients at risk of myocardial injury.

Basophils and mast cells are among the principal inducers of Th2 responses and have a crucial role in allergic and anti-parasitic protective immunity. Basophils can function as antigen-presenting cells that bind antigens on their surface and boost humoral immune responses, inducing Th2 cell differentiation. Their depletion results in lower humoral memory activation and greater infection susceptibility. Basophils seem to have an active role upon immune response to SARS-CoV-2. In fact, a coordinate adaptive immune response to SARS-CoV-2 is magnified by basophils. It has been observed that basophil amount is lower during acute disease with respect to the recovery phase and that the grade of this depletion is an important determinant of the antibody response to the virus. Moreover, mast cells, present in a great quantity in the nasal epithelial and lung cells, participate in the first immune response to SARS-CoV-2. Their activation results in a hyperinflammatory syndrome through the release of inflammatory molecules, participating to the “cytokine storm” and, in a longer period, inducing pulmonary fibrosis. The literature data suggest that basophil counts may be a useful prognostic tool for COVID-19, since their reduction is associated with a worse prognosis. Mast cells, on the other hand, represent a possible therapeutic target for reducing the airway inflammation characteristic of the hyperacute phase of the disease.

Background: TiO2 nanoparticles (TiO2 NPs) are the nanomaterial most produced as an ultraviolet (UV) filter. However, TiO2 is a semiconductor and, in nanoparticle size, is a strong photocatalyst, raising concerns about photomutagenesis. Mesoporous silica nanoparticles (MSN) were synthetized incorporating TiO2 NPs (TiO2@MSN) to develop a cosmetic UV filter. The aim of this study was to assess the toxicity of TiO2@MSN, compared with bare MSN and commercial TiO2 NPs, based on several biomarkers. Materials and Methods: Human peripheral blood mononuclear cells (PBMC) were exposed to TiO2@MSN, bare MSN (network) or commercial TiO2 NPs for comparison. Exposed PBMC were characterized for cell viability/apoptosis, reactive oxygen species (ROS), nuclear morphology, and cytokines secretion. Results: All the nanoparticles induced apoptosis, but only TiO2 NPs (alone or assembled into MSN) led to ROS and micronuclei. However, TiO2@MSN showed lower ROS and cytotoxicity with respect to the P25. Exposure to TiO2@MSN induced Th2-skewed and pro-fibrotic responses. Conclusions: Geno-cytotoxicity data indicate that TiO2@MSN are safer than P25 and MSN. Cytokine responses induced by TiO2@MSN are imputable to both the TiO2 NPs and MSN, and, therefore, considered of low immunotoxicological relevance. This analytical assessment might provide hints for NPs modification and deep purification to reduce the risk of health effects in the settings of their large-scale manufacturing and everyday usage by consumers.

Knowledge on Bi metabolism in laboratory animals refers to studies at "extreme" exposures, i.e. pharmacologically relevant high-doses (mg kgAnimals were intraperitoneally injected with 0.8 μg Bi kgAt 24 h post injection the kidney contained by far the highest Bi concentration (10 ng gAt the best of our knowledge the present paper represents the first in vivo study, on the basis of an environmental toxicology approach, aiming at describing retention and binding of Bi in the rat at tissue, intracellular and molecular levels.

The number of the applications of bismuth (Bi) is rapidly and remarkably increasing, enhancing the chance to increase the levels to which humans are normally daily exposed. The interest to Bi comes also from the potential of Bi-based nanoparticles (BiNPs) for industrial and biomedical purposes. Like other metal-based NPs used in nanomedicine, BiNPs may release ultratrace amounts of Bi ions when injected. The metabolic fate and toxicity of these ions still needs to be evaluated. At present, knowledge of Bi metabolism in laboratory animals refers almost solely to studies under unnatural "extreme" exposures, i.e. pharmacologically relevant high-doses (up to thousand mg kgRats were intraperitoneally injected with 0.8 μg Bi kg24 h after the administration, the blood concentration of Bi was 0.18 ng mLOn the basis of an environmental biochemical toxicology approach, we have undertaken a study on the metabolic patterns of Bi

For several years now, medicine has been benefiting from the contribution of nanoparticles (NPs) technology for both diagnosis and therapy. They can be used as adjuvants, being capableThe review focuses on experimental use of NPs as adjuvants/carriers for allergen immunotherapy (AIT). Human clinical trials conducted so far are discussed.Results of experimental studies and recent clinical trials support the use of NPs as carrier/adjuvant in AIT. Comparisons between NP-based and classical AIT are needed, to show the usefulness of the NP-based approach. However, there are still unsolved problems: the persistence of non-degradable NPs with possible toxicological consequences, and the formation of the protein corona around the NPs, which could alter their activity and fate. Virus-like particles seem the most promising NPs for allergy treatment, as for other vaccines. Over the next decade, NP-based AIT will be largely used to treat allergic disorders.

The interaction between NPs and immune system has been demonstrated, however, the data available are limited. Among all traits, i.s. hydrophilicity, lipophilicity, catalytic activity, composition, electronic structure, capacity to bind or coat surface species and solubility, the dimension, and consequently the surface area, seems to be the main factor that contribute to the interactions of NPs with biological tissues and immune system in particular. Certain NPs accumulate to regional lymph nodes, where they can be taken up and processed by dendritic cells, interact with self-proteins and, hence, modify their antigenicity and elicit altered immune responses and even autoimmunity. Other NPs may induce allergic sensitization, i.e. allergic contact dermatitis to Pd. In vitro studies demonstrated that NPs can modulate cytokine production toward Th1 (Pl, Pd, Ni, Co) or Th2 (Ti, mw and sw Carbon) production patterns. Some NPs have been linked to allergic sensitization, however, It is unlikely that NPs can act as a hapten inducing a specific IgE production, likely they can act as adjuvant and induce a specific pattern of cytokines, antibody and cells that favor allergic sensitization to environmental allergens. Furthermore, NPs demonstrated pro-inflammatory effects in the lung in experimental animal with increased expression on IL-1beta, MIP-1alpha, MCP-1, MIP-2, keratinocyte chemoattractant, TARC, GM-CSF, MIP-1alpha and activation of the stress-activated MAPKs p38 and JNKs. All considered, the available data suggest that through the elicitation of an oxidative stress mechanism, engineered NPs may contribute to pro-inflammatory disease processes in the lung, particularly allergy.

Background Knowledge on Bi metabolism in laboratory animals refers to studies at “extreme” exposures, i.e. pharmacologically relevant high-doses (mg kg−1 b.w.) in relation to its medical use, or infinitesimal doses (pg kg−1b.w.) concerning radiobiology protection and radiotherapeutic purposes. There are no specific studies on metabolic patterns of environmental exposure doses (ultratrace level, μg kg−1 b.w.), becoming in this context Bi a “heavy metal fallen into oblivion”. We previously reported the results of the metabolic fate of ultratrace levels of Bi in the blood of rats [ 1 ]. In reference to the same study here we report the results of the retention and tissue binding of Bi with intracellular and molecular components. Methods Animals were intraperitoneally injected with 0.8 μg Bi kg−1 b.w. as 205+206Bi(NO)3, alone or in combination with 59Fe for the radiolabeling of iron proteins. The use of 205+206Bi radiotracer allowed the determination of Bi down to pg fg−1 in biological fluids, tissues, subcellular fractions, and biochemical components isolated by differential centrifugation, size exclusion chromatography, solvent extraction, precipitation, immunoprecipitation and dialysis. Main findings At 24 h post injection the kidney contained by far the highest Bi concentration (10 ng g−1 wt.w.) followed by the thymus, spleen, liver, thyroid, trachea, femur, lung, adrenal gland, stomach, duodenum and pancreas (0.1 to 1.3 ng g−1 wt.w.). Brain and testis showed smaller but consistently significant concentrations of the element (0.03 ng g−1 wt.w). Urine was the predominant route of excretion. Intracellularly, liver, kidney, spleen, testis, and brain cytosols displayed the highest percentages (35%–58%) of Bi of homogenates. Liver and testis nuclei were the organelles with the highest Bi content (24 % and 27 %). However, when the recovered Bi of the liver was recorded as percent of total recovered Bi divided by percent of total recovered protein the lysosomes showed the highest relative specific activity than in other fractions. In the brain subcellular fractions Bi was incorporated by neuro-structures with the protein and not lipidic fraction of the myelin retaining 18 % of Bi of the total homogenate. After the liver intra-subcellular fractionation: (i) 65 % of the nuclear Bi was associated with the protein fraction of the nuclear membranes and 35 % with the bulk chromatin bound to non-histone and DNA fractions; (ii) about 50 % of the mitochondrial Bi was associated with inner and outer membranes being the other half recovered in the intramitochondrial matrix; (iii) in microsomes Bi showed a high affinity (close to 90 %) for the membranous components (rough and smooth membranes); (iv) In the liver cytosol three pools of Bi-binding proteins (molecular size > 300 kDa, 70 kDa and 10 kDa) were observed with ferritin and metallothionein–like protein identified as Bi-binding biomolecules. Three similar protein pools were also observed in the kidney cytosol. However, the amount of Bi, calculated in percent of the total cytosolic Bi, were significantly different compared to the corresponding pools of the liver cytosol. Conclusions At the best of our knowledge the present paper represents the first in vivo study, on the basis of an environmental toxicology approach, aiming at describing retention and binding of Bi in the rat at tissue, intracellular and molecular levels.

Background The number of the applications of bismuth (Bi) is rapidly and remarkably increasing, enhancing the chance to increase the levels to which humans are normally daily exposed. The interest to Bi comes also from the potential of Bi-based nanoparticles (BiNPs) for industrial and biomedical purposes. Like other metal-based NPs used in nanomedicine, BiNPs may release ultratrace amounts of Bi ions when injected. The metabolic fate and toxicity of these ions still needs to be evaluated. At present, knowledge of Bi metabolism in laboratory animals refers almost solely to studies under unnatural “extreme” exposures, i.e. pharmacologically relevant high-doses (up to thousand mg kg−1) in relation to its medical use, or infinitesimal-doses (pg kg−1 as non-carrier-added Bi radioisotopes) for radiobiology protection, diagnostic and radiotherapeutic purposes. No specific study exists on the “metabolic patterns” in animal models exposed to levels of Bi, i.e. at “environmental dose exposure” that reflect the human daily exposure (μg kg−1). Methodology Rats were intraperitoneally injected with 0.8 μg Bi kg−1 bw as 205+206Bi(NO)3 alone or in combination with 59Fe for radiolabelling of iron proteins. The use of 205+206Bi radiotracers allowed the detection and measurement down to pg fg−1 of the element in the blood biochemical compartments and protein fractions as isolated by differential centrifugation, size exclusion- and ion exchange chromatography, electrophoresis, solvent extraction, precipitation and dialysis. Results 24 h after the administration, the blood concentration of Bi was 0.18 ng mL−1, with a repartition plasma/red blod cells (RBC) in a ratio of 2:1. Elution profiles of plasma from gel filtration on Sephadex G-150 showed four pools of Bi-binder proteins with different molecular sizes (> 300 kDa, 160 kDa, 70 kDa and Conclusions On the basis of an environmental biochemical toxicology approach, we have undertaken a study on the metabolic patterns of Bi3+ ions in rats at tissue, subcellular and molecular level with the identification of cellular Bi-binding components. As a first part of the study the present work reports the results concerned with the metabolic fate of ultratrace levels of 205+206Bi(NO)3 in the blood.

Objectives The inflammatory effects of organic sub-10 nm particles generated and emitted from a diesel engine fueled with a biodiesel and a commercial diesel oil are analyzed in this paper. Diesel combustion is the major sources of ultrafine particles (UFP) in the environment, particularly in urbanized areas. In the last years, there is an increasing use of biomass-derived fuels because they are a renewable source of energy that may mitigate climate change through the reduction of net CO 2 with respect to conventional fossil fuels. Although there is a general agreement on biofuels ability to reduce conventional pollutants, new and potentially harmful pollutants can be formed during biofuel combustion. In particular, the emission of sub-10 nm particles is strongly increased with respect to that of larger soot particles. Methods Organic sub-10 nm particles are separated from larger sizes particulate matter by collection in water suspension for toxicological and inflammatory tests. After exposure to sub-10 nm particles, the effects on proliferation, apoptosis and secretion of cytokines, chemokines and growth factors networks production is analyzed in immortalized non-tumorigenic human dermal keratinocyte cell line (HaCaT) and human alveolar epithelial-like cells (A549). Results and conclusion Nanoparticles exert different cytotoxic effects in the two cell lines, suggesting that the dermal way of exposure is more sensitive than the inhalant way. These differences are most evident in the secretion of pro-inflammatory, angiogenic and proliferative cytokines and chemokines whose expression is more finely modulated in HaCaT cells compared to A-549 cells. Considering the size of these particles, it is important to promote the culture of prevention also for the dermal way in particularly exposed workers.

Background: TiO2 nanoparticles (TiO2 NPs) are the nanomaterial most produced as an ultraviolet (UV) filter. However, TiO2 is a semiconductor and, in nanoparticle size, is a strong photocatalyst, raising concerns about photomutagenesis. Mesoporous silica nanoparticles (MSN) were synthetized incorporating TiO2 NPs (TiO2@MSN) to develop a cosmetic UV filter. The aim of this study was to assess the toxicity of TiO2@MSN, compared with bare MSN and commercial TiO2 NPs, based on several biomarkers. Materials and Methods: Human peripheral blood mononuclear cells (PBMC) were exposed to TiO2@MSN, bare MSN (network) or commercial TiO2 NPs for comparison. Exposed PBMC were characterized for cell viability/apoptosis, reactive oxygen species (ROS), nuclear morphology, and cytokines secretion. Results: All the nanoparticles induced apoptosis, but only TiO2 NPs (alone or assembled into MSN) led to ROS and micronuclei. However, TiO2@MSN showed lower ROS and cytotoxicity with respect to the P25. Exposure to TiO2@MSN induced Th2-skewed and pro-fibrotic responses. Conclusions: Geno-cytotoxicity data indicate that TiO2@MSN are safer than P25 and MSN. Cytokine responses induced by TiO2@MSN are imputable to both the TiO2 NPs and MSN, and, therefore, considered of low immunotoxicological relevance. This analytical assessment might provide hints for NPs modification and deep purification to reduce the risk of health effects in the settings of their large-scale manufacturing and everyday usage by consumers.

While nanotechnology is growing exponentially, the knowledge of the impact of nanoparticles (NPs) on public health and the environment is limited so far. Current nanomaterial research is focused on the applications of nanotechnology, whereas there is little information on exposure assessment and risk characterization associated with NPs. Therefore, it is essential that the factors influencing NPs associated hazards be studied. This review seeks to survey and evaluate the current literature in order to better understand the impact of both airborne and engineered NPs exposure, the mechanisms at the cellular level, and the factors influencing their immunotoxicity. In fact, NPs do have immunotoxicological significance, as immune cells in the bloodstream and tissues do act to eliminate or interact with NPs. Proper characterization of the NPs as well as understanding the processes occurring on the NPs surface when in contact with biological systems is crucial to predict or exclude toxicological effects.

Introduction The risk for a beekeeper to become allergic to bee venom is higher than the general population. The possibility that they develop an allergy is greater when rarely bite with 2/3 month interval. On the contrary, when bites are simultaneous or tight over time the probability of allergy decreases. Beekeepers who receive more than 200 stings do not develop venom allergy. In general, subjects developing a reaction limited to the skin have 70% possibility of a spontaneous recovery. On the contrary, people haveing a systemic reaction tends to show the same or greater reaction when restung. Discussion Work suitability of bee allergic beekeepers, which had a systemic reaction is a relevant problem for occupational doctors. They should be prescribed appropriate DPI and provided of auto-injectable adrenaline as emergency treatment, sure that they received the necessary training. Furthermore, it is desirable that every allergic subject receives a desensitising treatment, as it is efficacious in 95% of patients. The treatment will last for 5 years, except for subjects with high basal tryptase who should be treated for a life-time, as the risk of anaphylaxis reappears after the discontinuation of an already effective immunotherapy. The cardiac involvement during anaphylaxis is very frequent with the picture of Kounis Syndrome (KS), characterised by infarction induced by the effects on coronaries of mast cell chemical mediators. In particular, histamine, usually vasodilator agent, can induce vasoconstriction subjects with coronary endothelial lesions. In this situation, the coronary spasm worsens the perfusion of a tachy heart, already with increased blood demand, with a potentially life-threatening ischemia. Furthermore, in a subject developing a KS the administration of adrenaline should be carefully evaluated as adrenaline, having vasoconstriction effects, can worsen the myocardial ischemia. Conclusions It is our opinion that work suitability cannot be granted to beekeepers who developed KS with.

Aim of the session To discuss occupational allergies in basic mechanisms, testing and newer clinical topics 1Dr. A. Fourie, 2Dr. L. Wengenroth, 3Dr. E. Kuroda, 4Dr. M. Di Gioacchino 1National Institute for Occupational Health, National Health Laboratory Services, Johannesburg, South Africa 2Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Munich, Germany 3Laboratory of Adjuvant Innovation, Centre for Vaccine and Adjuvant Research (CVAR), National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan 4Unit of Immunotoxicology and Allergy, CeSI-MET, G. d’Annunzio University, Chieti, Italy

Introduction TiO2-NPs are the most produced nanomaterial as UV filters. They are considered as nontoxic at the exposure levels of the occupational environments; nevertheless, potentially dangerous organic molecules can be formed due to photocatalysis. Mesoprous silica (SiO2) nanoparticles (MSN) incorporating Ti-nano were produced to improve their properties. We studied whether human lymphocytes/monocytes can be the target of a toxic action of all these NPs. Methods Activated/quiescent huPBMCs were exposed ex-vivo to: TiO2-NPs (21 nm); MSN (100 nm); TiO2-MSN (4.4 nm TiO2 into MSN pores). They were characterised for: cell viability/apoptosis by MTT and Annexin-V; ROS by DCFH oxidation; nuclear morphology by fluorescence microscopy; cytokines by ELISA. Results The viability of activated lymphocytes exposed to the highest doses all NPs was significantly reduced. All NPs induced apoptosis, but only TiO2-NPs induced ROS. IL-2, IL-17, IFN-g were downmodulated by all; MSNs were associated with increased IL-1β and IL-4 secretion; TiO2-NPs induced IL-10, TNF-α and IL-23. Conclusion Different patterns of cytokine in response to the three different NPs tested: they are all immunosuppressive, but only TiO2-MSN seem to act as pro-inflammatory and pro-allergic agents. The presence of TiO2 in MSN appear to influence the effects of these larger NPs, possibly related to its pro-oxidative and pro-apoptotic effect.

Introduction Exposition to asbestos may cause adverse health effects, but a clear relationship between mineralogy and texture of fibres versus toxicity is still lacking. Toxicological studies can be properly interpreted and compared only if quantitative features of fibres are determined. Methods Amphibole fibres were characterised by XRPD, FTIR, SEM-EDS and EMP-WDS. Fibres deposited from solutions of 0.1, 1, 10, 25, 50, 75 and 100 mg/L were counted using SEM images. The single vs agglomerated fibres was assessed. The viability of human lymphocytes exposed to the fibres was investigated by MTT test. Results Only crystals with definite stoichiometry are present. At 0.1 and 1 mg/L the fibres are well separated, whereas between 1 and 10 mg/L they start to agglomerate. In vitro tests performed on fibres deposited at the same concentrations show that the cytotoxic effect rate decreases for asbestos concentration >10 mg/L. Conclusions Considering that the mineralogy is constant, the decreasing rate of toxicity suggests that the hazardous potential must be attributed mainly to the single fibres, while the agglomerated fibres, whose amount increases strongly for increasing total fibres play a minor role.

Introduction The inflammatory effects of organic sub-10nm particles generated and emitted from a diesel engine fueled with a biodiesel and a commercial diesel oil are analysed in this paper. Diesel combustion is the major sources of ultrafine particles (UFP) in the environment, particularly in urbanised areas. In the last years, there is an increasing use of biomass-derived fuels because they are a renewable source of energy that may mitigate climate change through the reduction of net CO2 with respect to conventional fossil fuels. Although there is a general agreement on biofuels ability to reduce conventional pollutants, new and potentially harmful pollutants can be formed during biofuel combustion. In particular, the emission of sub-10nm particles is strongly increased with respect to that of larger soot particles. Methods Organic sub-10nm particles are separated from larger sizes particulate matter by collection in water suspension for toxicological and inflammatory tests. After exposure to sub-10nm particles, the effects on proliferation, apoptosis and secretion of cytokines, chemokines and growth factors networks production is analysed in immortalised non-tumorigenic human dermal keratinocyte cell line (HaCaT) and human alveolar epithelial-like cells (A549). Results Nanoparticles exert different cytotoxic effects in the two cell lines, suggesting that the dermal way of exposure is more sensitive than the inhalant way. These differences are most evident in the secretion of pro-inflammatory, angiogenic and proliferative cytokines and chemokines whose expression is more finely modulated in HaCaT cells compared to A-549 cells. Conclusion Considering the size of these particles, it is important to promote the culture of prevention also for the dermal way in particularly exposed workers.

Aim of the session To discuss immunotoxicological alterations caused by occupational and envuironmental substances 1Dr. Y. Nishimura, 2Dr. Q. Niu, 3Dr. P. Pedata, 4Dr. T. Otsuki 1Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan 2School of Public Health, Shanxi Medical University, Taiyuan, China 3Seconda Universita degli Studi di Napoli, DMS-SIMLL, Naples, Italy 4Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan

The 2017 Nobel Prize for Physiology or Medicine, awarded for the discoveries made in the past 15 years on the genetic and molecular mechanisms regulating many physiological functions, has renewed the attention to the importance of circadian rhythms. These originate from a central pacemaker in the suprachiasmatic nucleus in the brain, photoentrained via direct connection with melanopsin containing, intrinsically light-sensitive retinal ganglion cells, and it projects to periphery, thus creating an inner circadian rhythm. This regulates several activities, including sleep, feeding times, energy metabolism, endocrine and immune functions. Disturbances of these rhythms, mainly of wake/sleep, hormonal secretion and feeding, cause decrease in quality of life, as well as being involved in development of obesity, metabolic syndrome and neuropsychiatric disorders. Most immunological functions, from leukocyte numbers, activity and cytokine secretion undergo circadian variations, which might affect susceptibility to infections. The intensity of symptoms and disease severity show a 24 h pattern in many immunological and allergic diseases, including rheumatoid arthritis, bronchial asthma, atopic eczema and chronic urticaria. This is accompanied by altered sleep duration and quality, a major determinant of quality of life. Shift work and travel through time zones as well as artificial light pose new health threats by disrupting the circadian rhythms. Finally, the field of chronopharmacology uses these concepts for delivering drugs in synchrony with biological rhythms.

Nickel is one of the most common skin sensitizers, usually responsible for allergic contact dermatitis (ACD). The ingestion of nickel-rich foods is also able to elicit cutaneous (in the absence of physical contact with nickel) and gastrointestinal symptoms in some subjects with nickel ACD, a condition referred to as systemic nickel allergy syndrome (SNAS). The pathogenesis of this disease involves both Th1 and Th2 cells and cytokines, with involvement of both CD8- and CD4-positive T lymphocytes. Clinical aspects include flares of previous ACD lesions and/or positive nickel patch test reactions, widespread eczema, and gastrointestinal disturbance essentially characterized by meteorism and colic. This diagnosis may be suspected in patients with nickel ACD whose gut and skin symptoms disappear or improve after a low nickel diet. Essential for the diagnosis is to confirm that symptoms reappear after a double-blind placebo-controlled oral nickel challenge. In such cases, the low nickel diet can be used as treatment. Of note, to maintain a nickel-free diet for a long time may strongly impact a patient’s quality of life. Therefore, a desensitization treatment should be considered in these patients. Nickel hyposensitization is effective in patients suffering from SNAS. The majority of such patients can safely ingest nickel-containing foods after 1 year of treatment. Clinical experience in patients with ACD alone, although positive and encouraging, is scarce in terms of the number of patients treated and length of the hyposensitization course, which is usually followed, after a relatively short period of time, by a relapse of cutaneous symptoms. In any case, nickel hyposensitization is able to modulate immune responses to nickel by restoring a state of tolerance that seems to be mediated by T regulatory lymphocytes.