Blood pressure changes and polycyclic aromatic hydrocarbons in outdoor workers.

OBJECTIVES: Everyday outdoor workers are exposed to chemicals including the polycyclic aromatic hydrocarbons (PAHs). The aim of the study is to evaluate the relationship between hydroxypyrene and blood pressure in outdoor workers. MATERIALS AND METHODS: 374 subjects of both sexes entered the study. We evaluated the assay of urinary hydroxypyrene (1-HOP); their blood pressure (BP) was measured in upright position and in the supine position and the correlation between the levels of 1-HOP and BP was assessed using Pearson test and linear multiple regression. RESULTS: The results obtained show that in the total sample the levels of urinary 1-OHP are negatively associated with systolic and diastolic BP in supine position and in upright position. The significance is maintained despite the stratification of the sample according to age; in non-smokers we found a negative relationship between 1-OHP and differential blood pressure, both systolic and diastolic. CONCLUSIONS: The results of the study suggest that occupational exposure to PAHs may be able to significantly influence the blood pressure probably acting on the autonomic nervous system.

Perception of occupational risk by rural workers in an area of central Italy.

The aim of this study is to analyze the subjective perception of risks for rural workers in Abruzzo, an area of central Italy. A group of 273 workers were asked to fill in a questionnaire which included, apart from general information, questions relative to six different types of risks normally found in the field of agriculture. The types of risks considered were: falling from a height, manually moving loads, overturning/accident whilst driving an agricultural tractor, noise and vibration, use of pesticides, the risk of being cut/injured. The workers were requested to assess, on a scale of 1 to 3, both the probability of an accident taking place and the consequent damage which could result from each of the risks considered. The assessment of the risks provided by the workers was related to the objective assessment of the risks carried out by the study group, also on the basis of objective data provided by INAIL (Italian insurance company) indexes, to highlight the eventual under/over estimations of risk. Furthermore, the possible correlation was evaluated between having received specific training regarding work safety and the workers perception of the risk. The results showed that approximately 11 percent of the workers do not consider their job as being dangerous; the risk perceived by the workers is higher for accidents that cause an immediate injury compared to those which cause professional illnesses, except the risk deriving from noise/vibrations. A direct correlation was found between the job as being dangerous and having attended courses on accident prevention.

[Innovation in the ergonomic procedures for evaluating risk in building activities of the Abruzzo region (Italy)]. / Innovazione nelle procedure ergonomiche per la valutazione del rischio nel settore edile in Abruzzo.

After the earthquake of L'Aquila, INAIL further stimulated the local Universities to train specialists in the prevention of occupational risks on construction sites. Since 2005 the University of Chieti-Pescara evaluated occupational stress (through the Karasek's JCQ) as well as perception of occupational risk of the building workers. Moreover, procedures (including planning) in the field of building technology were analyzed. The perception of job strain of the workers in building activities were high because of elevated job demand and low decision latitude. The risk perception was higher regarding dangers producing immediate injury. There was no direct relationship between considering the job dangerous and having attended training courses, while the relationship between risk perception and past injury events was marked. At present, we are also evaluating, by instrumental methods, the biomechanical overload of workers, due to the main repetitive and forceful manual activities.

Work stress and innate immune response.

Several reports highlight the relationship between blood NK cytotoxic activity and life style. Easy life style, including physical activity, healthy dietary habits as well as good mental health are characterized by an efficient immune response. Life style is related to the type of occupational activity since work has a central part in life either as source of income or contributing to represent the social identity. Not only occupational stress, but also job loss or insecurity are thus considered serious stressful situations, inducing emotional disorders which may affect both neuroendocrine and immune systems; reduced reactivity to mitogens and/or decreased blood NK cytotoxic activity was reported in unemployed workers or in those with a high perception of job insecurity and/or job stress. Although genetic factors have a key role in the pathogenesis of autoimmune disorders, occupational stress (as in night shifts) was reported associated to an increased incidence of autoimmune disorders. Monitoring blood NK response may thus be included in the health programs as an indirect index of stressful job and/or poor lifestyle.

Immunotoxicity of nanoparticles.

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.

[The development of organizational comfort: organizational training as strategic instrument for changing]. / Lo sviluppo del benessere organizzativo: la formazione organizzativa come leva strategica per il cambiamento.

The organizational comfort has been defined as the relationship between people and work environment. The supervisor's functions imply organizing and relation competences, listening and observation, communication and negotiation. Unfortunately, the reality is quite different: there are often situations of communication disorder between the supervisor and the worker, where the first, unaware of his role and responsibility, doesn't understand the worker's needs, doesn't communicate rightly the risk, doesn't develop any emphatic attitude and organize work without thinking to individual inclinations and limitations. The worker perceives this situation as increasing sensation of tiredness and working stress. The workers, often involved in this organization, have to ask overtime medical examinations to obtain some limitations. Observing this big increase of limitations in some firms with working people relatively young, we have decided to elaborate an experimental project involving both the occupational doctor and the psychologist. We analyzed the relations between the supervisor and the worker, with the aim to increase organizational comfort, through the diffusion of anonymous questionnaires or training courses about behaviour analyses and communication strategies, verifying any possible modifications of the organization after our intervention.

[Comparison of the training schemes of the specialization schools of the public health area: a rational basis for a proposal of a core curriculum for the university training programme contained in article 38 of Legislative Decree (D.Lgs) 81/2008]. / Confronto dei contenuti formativi delle scuole di specializzazione dell'Area di Sanità Pubblica: le basi razionali per una proposta di core curriculum per il percorso formativo universitario ex art. 38, D.Lgs 81/2008.

A document by the B. Ramazzini College of University Teachers of Occupational Medicine of the Italian Society of Occupational Health and Industrial Hygiene (S.I.M.L.I.I). The aim of this document was to compare the professional competence, training profile and core curricula of the three main specialization courses in the Public Health postgraduate medical area, i.e., Occupational Medicine, Hygiene and Preventive Medicine, and Forensic Medicine, such as contained in the Ministerial Decree (D.M) of 1 August 2005. We set out to identify, using clear and objective criteria, the knowledge and skills that specialists in Hygiene or Forensic Medicine must develop, in accordance with Art. 38 of the new Italian law on safety ahd health at work (D.Lgs 81/2008), in order to be authorized to perform occupational health activities as "Competent Physicians" (CP). The comparison revealed significant differences in structure and content among the three courses. In particular, compared to the course in Occupational Medicine, the courses in Hygiene and in Forensic Medicine both lack clinical training, including diagnostic and therapeutic skills, risk-oriented occupational health activities, biological monitoring, assessment of individual susceptibility, and clinical or instrumental procedures to prevent and detect occupational diseases. Furthermore, the specialization course in Hygiene lacks any training regarding the criteria and methods for assessing the individual worker's fitness for work, while the course in Forensic Medicine lacks any training in occupational risk assessment and management. From this comparison, a list was derived of the education and training debits that specialists in Hygiene or Forensic Medicine should cover (credits) in order to be authorized to perform CP activities as indicated by the new law. A core curriculum is proposed here, based on the corresponding credits, for use as a reference.

[In vitro study on the immune effects of the exposure to palladium nanoparticles]. / Studio in vitro sugli effetti immunitari dell'esposizione a nanoparticelle di palladio.

Pd allergic contact dermatitis is increasing in the general population; aim of this preliminary study was to determine, in women with Pd sensitization, the cytokine release from PBMC exposed to Pd nanoparticles similar to those emitted from catalytic converters. PBMC of 8 non-atopic and of 5 Pd sensitized women were incubated with LPS stimulation in presence of Pd nanoparticles (5-10 nm) or potassium hexa-chloropalladate 10(-5) and 10(-6) M. This Pd salt inhibited IFN-gamma, TNF-alpha, IL-10 and IL-17 release from PBMC of non-atopic women, whereas Pd nanoparticles enhanced the release of IFN-gamma and inhibited that of TNF-alpha and IL-17. In the Pd-sensitized women, with high basal values of cytokine release, the 10(-5) M Pd salt (but not Pd nanoparticles) inhibited IL-10 and IL-17 release. In conclusion, Pd salt inhibits the cytokine release from PBMC, whereas Pd nanoparticles exert modulatory effects enhancing release of IFN-gamma which plays an important role in autoimmune diseases.

[Effects of occupational stress and job insecurity on the immune response]. / Effetto dello stress occupazionale e dell'insicurezza di inserimento lavorativo sull'efficienza del sistema immunitario.

The immune system responds to environmental signals. High blood NK activity characterizes individuals with a good life style and mental health condition or those exerting physical activity. Mental instability, depression and a poor life style exert opposite effects. A poor work environment with low social support or repetitive and shift work, as well as unemployment, are shown to affect the immune response, inducing autoimmune disorders or reducing NK cell activity. We studied anxiety, job strain and insecurity and the NK cell activity of 118 men and 68 women working in a university. A group of older male employees with high job strain and anxiety showed lower NK cell activity. Young male employees with temporary jobs showed reduced NK cell activity, while male doctors in training in Dental School underwent increased job strain, but anxiety, job insecurity and immune response were within a normal range. Analysis of all the data of the men showed that anxiety and job insecurity (more than occupational stress) reduce NK cell activity, thus affecting the health status. On the other hand, the results of this study on women may not exclude that nurses working in hospital in a stressful work environment may show reduced immune response.

Chlamydia pneumoniae and atherosclerosis: the role of mast cells.

Chlamydia pneumoniae (C. pneumoniae), a respiratory pathogen, has been implicated in the pathogenesis of atherosclerosis, an inflammatory progressive disease, characterized by the formation of atherosclerotic plaques. Among several types of inflammatory cells involved in the atherogenesis process, recently particular attention has been directed toward the mast cells. Experimental studies have provided several mechanisms by which C. pneumoniae and mast cells could play a role in all stages of atherosclerosis, from initial inflammatory lesions to plaque rupture. C. pneumoniae, as well as mast cells, may actively participate both through the production of cytokines and matrix-degrading metalloproteinases and by provoking apoptosis of atheroma-associated vascular cells, key events in plaque rupture. This mini-review provides a brief overview on adventitial inflammatory effects of C. pneumoniae and mast cells and their potential role in plaque instability. In addition, in this paper we review the role of mast cells in innate immunity.

Occupational stress, job insecurity and perception of the health status in Italian teachers with stable or temporary employment.

The object of this study is to analyse job stress and insecurity and the perception of symptoms (health status) of 374 teachers (30 women and 74 men) with stable or temporary employment in schools in Pescara, a town in Central Italy. Job strain and job insecurity were analysed by an Italian version of the Karasek?s questionnaire, the perception of the health status by a 12 item test, and state and trait anxiety by STAI I and STAI II. There were no significant differences depending on the type of school. The young women with temporary contracts showed only higher levels of job insecurity than the women with stable employment, while those over 50 years old also showed more elevated values of job strain. Men with temporary contracts showed higher levels of both job insecurity and state and trait anxiety. The following highly significant correlations were observed: a) in women, job strain and perception of symptoms vs STAI I and STAI II (p<0.001); b) in men, job strain, job insecurity and perception of symptoms vs STAI II; job strain vs perception of symptoms as well as a negative correlation of decision latitude vs job insecurity, STAI I and STAI II (p<0.01). These results highlight differences in the perception of job insecurity between men and women. In particular, the decision latitude (skill decision + decision authority) plays an important role in men; temporary employment is mainly related to anxiety in men, while anxiety enhances the perception of poor health status mainly in women.

Substance P upregulates LTB4 in rat adherent macrophages from granuloma induced by KMnO4.

Substance P (SP) is an important neuropeptide involved in neurogenic inflammation and most of its pathophysiological functions are mediated through binding to the neurokinin-1 receptor. SP exerts various proinflammatory actions on immune-cells, including macrophages. Several compounds such as cytokines have the capacity to activate and stimulate macrophages to produce arachidonic acid oxygenation and lipoxygenation products. Leukotriene B4 (LTB4) is one of the most important mediators of leukocyte activation in acute and chronic inflammatory reactions. LTB4 stimulates chemotaxis, lysosomal enzyme release, and cell aggregation. In this report, we studied the effect of SP on rat adherent granuloma macrophages (RAGMs). The chronic granuloma in rat was induced by dorsal injections of a potassium permanganate (KMnO4) saturated crystal solution (200 microl of a 1:40 dilution). After 7 days, all rats developed a subcutaneous granuloma in the injection site from which infiltrated macrophages were extracted, isolated, and cultured in vitro. We tested the hypothesis that SP stimulates the production of LTB4 in RAGMs and increases lipoxygenase expression. Here we show that the cell-free supernatant of RAGMs stimulated with SP (10 microM), resulted in statistically significant increases of LTB4 Preincubation of RAGMs with NDGA (nordihydroguaiaretic acid (10 microM), completely abolished the production of LTB(4) in the supernatants and lipoxygenase expression on RAGMs challenged with SP, or the cation ionophore A23187 (positive control). Similar effects were obtained when the cells were pretreated with dexamethasone (10 microM). Our results suggest that SP is able to stimulate the release of LTB4 and lipoxygenase expression in macrophages from chronic inflammatory granuloma and provide further evidence for a neuroinflammatory pathway.

Autism and immunity: revisited study.

Autism spectrum disorder is of interest neurochemically because it represents a relatively homogeneous disorder with regard to disease development, abnormal cognitive development and intellectual development disturbance. A consistent finding in autistic children is a high number of mast cells and a high level of serotonin which is also found at elevated concentrations in the urine of autistic patients. In addition, a dysfunction of clinical conditions, such as gastrointestinal and immunological symptoms, is frequently noted in autistic children, however, IgE does not appear to be prevalent in these children but probably an increase of cytokines/chemokines produced by mast cells at an early age may play an important role. Therefore an immune hypothesis, involving also autoimmunity, is one possible pathogenetic mechanism in autism. In conclusion, mast cell activation could contribute to immune and neuroinflammatory abnormalities that are evident in patients with autism spectrum disorders.

The latest interleukin: IL-33 the novel IL-1-family member is a potent mast cell activator.

IL-33, a member of IL-1 family, induces the differentiation of T-cells (depending on the phosphorylation of MAPKs and NF-kB) and is involved in T-cell mediated immune responses. IL-33 is also involved in the production of IL-5, IL-4 and IL-13 and several chemokines. In this editorial we show the importance of IL-33 in allergic diseases and its role as an inflammatory cytokine. In addition, the induction of certain chemokines by IL-33 may candidate this new cytokine as a mediator in inflammatory and autoimmune diseases and may prove to be a therapeutic target for the prevention of these diseases.

Neuropeptide substance P induces mRNA expression and secretion of CXCL8 chemokine, and HDC in human umbilical cord blood mast cells.

PURPOSE: Mast cells play an important role in innate and acquired immunity and are thought to be the cellular origin of most proteases and cytokines. Substance P (SP) and its receptor, NK-1R, play critical roles in immune regulation in human and animal models of inflammation. METHODS: We used mature human cord blood mast cells (HCBMC) differentiated from cord blood CD34+ precursor activated with SP in culture. RESULTS: Our data indicate that Substance P strongly activates mature HCBMC in releasing CXCL8 expression and secretion ( CONTROL: 1.200 +/- 1.0; SP: 4.10 +/- 0.90; P < 0.01). Moreover, in a RT-PCR, HCBMC expressed CXCL8 mRNA after Substance P activation. Since calcium ionophore A23187 is a pharmacological activator that raises cytosolic free calcium ion concentraion and stimulates mast cells in the production and secretion of proinflammatory compounds, it was used as positive control. In addition, we found that HCBMCs generate the transcription of histidine decarboxylase (HDC), the enzyme responsible for the generation of histamine from histidine, after SP treatment. Since CXCL8 is a member of the CXC chemokine subfamily with potent chemotactic activity and is a primary inflammatory cytokine we conclude that our results, obtained from HCBMC cultures, a good and valid model in vitro, support the concept that the neurogenic system modulates inflammatory events by Substance P-mediated HCBMC chemokine CXCL8 release. CONCLUSION: The expression, synthesis and release of CXCL8 suggest an increase of inflammatory process in vivo mediated by the recruitment and infiltration of inflammatory cells in inflamed tissues.

How do rat cortical cells cultured with aluminum die: necrosis or apoptosis?

Aluminum (Al) exposure has been implicated as the cause of neural cells loss in several neurodegenerative diseases. Therefore, defining the mechanism of neural cell death in Al toxicity and degenerative diseases might lead to the development of therapeutic agents which promote neural cell survival. Furthermore, knowledge of cell death pathways might facilitate the discovery of treatments for neurodegeneration. However, the death mode of neural cells triggered by Al has not been firmly established. The present study focuses on understanding the pathway of cells death in cultured cortical cells treated with Al. Primary neurons cultured alone, astrocytes cultured alone, and neuron/astrocyte co-cultures obtained from newborn rats were incubated with Al at the concentrations of 0, 0.5, 1.0, or 2.0 mM for 72 h. Morphological changes were observed with an inverted phase microscope, a fluorescent microscope, and an electron microscope. Simultaneously, the rate of apoptosis was quantified with flow cytometry. Morphological characteristics of apoptosis such as cell shrinkage, aggregation and fragmentation of chromatin, membrane buds, and formation of membrane-bound apoptotic bodies were observed in Al-treated neurons, while none of these characteristics were found in Al-treated astrocytes. Quantitative results of apoptotic rates detected with flow cytometry indicated a typical apoptosis progression in neurons at various dosages. A concentration-dependent relationship between Al concentration and apoptotic rates confirmed that apoptosis is the prominent cause of cell death in primary cultured neurons, even at a concentration lower than 2 mM. Both necrosis and apoptosis are evident in neuron/astrocyte co-cultures, but the intensity of apoptosis is much less compared with that of neurons, suggesting that astrocytes may be especially important for neuronal survival in the presence of Al.

Is necroptosis a death pathway in aluminum-induced neuroblastoma cell demise?

Besides being an aggravating factor secondary to major physiological alterations in degenerative diseases, aluminum has also been considered as a risk factor in the etiology. Although many in vivo and in vitro data are in favor of apoptosis and necrosis being involved in Al induced neurodegenerative processes, there is considerable evidence that very complex events may contribute to neural cell death. Necroptosis, a novel cell death pathway, was recently reported to contribute to ischemia brain injury. It is different from, but associated with, apoptosis and necrosis, the two common major pathways of cell demise. In the present study, SH-SY5Y cells were put under stress by Al, a potential degenerative cell death inducer. Nec-1, a specific inhibitor, was used to identify necroptosis. The characteristics observed in Nec-1 and Al treated SH-SY5Y cells showed that necrotic morphological changes were reduced, and a sharp decrease of necrotic rate was detected. Besides, there were Al-induced mitochondria membrane potential decreasing, reactive oxygen species remaining, and autophagosomes declining. The mechanism of Nec-1s effect on cell death may be related to caspases pathways. To our best knowledge, this is the pioneer report on necroptosis in mixed human neural cell death pathways, which might offer a novel therapeutic target for neurodegenerative diseases, and an extended window for neuroprotection.

Combined effects of electromagnetic fields on immune and nervous responses.

In technologically developed countries, there is concern about hazards from electromagnetic fields (EMFs). Several studies have reported that immune and neuroendocrine systems exert an integrated response to EMF exposure. The aim of this review is to summarize the results of studies on the effect of low and high frequency EMF on immune and neuroendocrine systems on which our research group has been working for several years.

Immunotoxicity and sensitizing capacity of metal compounds depend on speciation.

Immunotoxicity of metal compounds is an issue of great importance due to the recent industrial application of metals with unknown toxicity on the immune system and the discovery of metal intermediary compounds not sufficiently studied yet. In this report we show results of our study on the immunotoxicity of the following metals: the Platinum group elements (Platinum, Palladium, Rhodium), Titanium and Arsenic. We applied functional and non functional assays and investigated both innate and adaptive immune systems, in particular, cell proliferation, cytokine production by PBMCs and O*2 production by neutrophils. We obtained the following results: only some Ti compounds (Titanocene, Ti ascorbate and Ti oxalate) show immunotoxicity. Trivalent As compounds (Sodium arsenite and tetraphenyl arsonium chloride) are more immunotoxic than the other investigated As compounds. Genotoxicity of Pt group compounds is in the following order: Pt > Rh > Pd. Immunotoxicity of Pt group compounds is in the following order: Pd > Pt > Rh. Lymphocytes and macrophages show a different reaction of neutrophils to metal toxicity. We can conclude that these studies show that metal immunotoxicity depends on speciation. In general speciation provides additional and often essential information in evaluating metal toxicity. However, there are many difficulties in applying speciation in investigating toxico-kinetic aspects to many metals, mainly due to the lack of information about the existence and significance of species and to the lack of analytical methods for measuring species in biological samples.

The relationship between Bcl-gene expression and learning and memory impairment in chronic aluminum-exposed rats.

Aluminum (Al), a known neurotoxin, has been implicated in Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Parkinsonism Dementia Complex, etc., and it causes extensive damage to the nervous system, including the impairment of learning and memory. However, to date, the mechanism of Al neurotoxicity has not been fully elucidated. Neuronal apoptosis has become a focus of interest, as it has been reported to play a key role in the impairment of learning and memory processes (Thompson, Science 267:1456, 1995). The Bcl-2 gene acts as an important effector for inhibiting apoptosis. In the present study we observe neuronal apoptosis in association with learning and memory impairment, as well as regional brain alterations in Bcl-2 expression in rats chronically exposed to Al. The chronic Al-intoxicated model was established by i.p. injection of AlCl3 in adult Sprague Dawley rats for 3 successive days, with one-day intervals, for 60 days. After exposure, the step-down test was performed to examine the behavioral reaction of the rats. Neuronal apoptosis and Bcl-2 protein expression in different regions of rat brain were then assessed by an immunohistochemical method. In the step-down test, the latency of Al-exposed rats was significantly lower than that of controls. Also, the number of performance errors in 5 minutes of exposure was significantly higher than that of controls. Neuronal apoptosis was extensive in the brain of Al-exposed groups, and the expressions of Bcl-2 protein in frontal cortex, cerebellum and hippocampus of Al-exposed rats was stronger. In conclusion, chronic Al-exposure in rats is associated with neuronal apoptosis in brain, and impaired learning and memory. Augmented Bcl-2 protein expression may be a stimulated compensatory mechanism.