Kounis Syndrome as First Manifestation of Allergic Sensitization.

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.

Occupational allergy: is there a role for nanoparticles?

All fields of industry are applying nanotechnologies for the development of advanced materials, there¬fore at present the number of workers exposed to nanosized materials are significantly increasing. Unfortunately, protective equipment for nanoparticles (NPs) is of uncertain efficacy so the risk of noxious effects, in particular allergic sensitization, on workers gives many concerns. At the same time, studies of allergic physiopathology demonstrated that the lack of prevention and treatment could result in invalidating dis¬eases that, in case of professional etiology, might imply removal from the job and compensation. Therefore, a deeper knowledge of the role of NPs in inducing allergic diseases is mandatory to implement the risk assessment and preventive measures for nanosafety in the workplace. The possibility that NPs favor, ex¬acerbate or directly induce allergy is being suggested by recent experimental investigations in cellular and animal models. Unfortunately, studies are heterogeneous and few data have received experimental confir¬mation, lacking reproducibility. What comes to attention is the uncertainty about the real plausibility of the observed experimental effects, as there are only a few reported cases of allergy onset or exacerbation for workers exposed to NPs. However, the potential for NPs to induce, favor or exacerbate allergies seems possible even though not completely demonstrated. This should be a greater incentive to carry out appro¬priate epidemiological studies that are lacking and really needed.

The persistence of allergen exposure favors pulmonary function decline in workers with allergic occupational asthma.

BACKGROUND: In asthmatics, a rapid decline in pulmonary function is observed, likely as a consequence of airways remodeling. Persistence of allergen exposure in patients with occupational asthma (OA) maintains chronic bronchial inflammation, resulting in a more severe lung function decline. Few studies were performed on the effects of allergen exposure cessation. OBJECTIVE: This study aims at evaluating the influence of allergen exposure cessation on respiratory decline in allergic asthmatic workers. METHODS: Two groups of workers with allergic OA were selected. The first group (30 workers) changed job after the diagnosis and was no more exposed to sensitizing allergens, and the second group (28 subjects) did not and, as a consequence of preventive measures in the work place, was exposed to a lower level of allergens. All were treated with conventional therapy, according to GINA protocols. FEV1 changes during a 12-year period were evaluated. RESULTS: Despite pharmacological therapy, the pulmonary function decay slope was steeper in workers continuously exposed to the sensitizing agent (even at reduced level) than in those with a complete cessation of exposure: final FEV1 loss was 512.5 ± 180 ml versus 332.5 ± 108 ml, respectively. The difference became significant after 4 years from the cessation of the exposure. CONCLUSIONS: The study shows that the cessation of the exposure to allergen in the work place appears the most effective measure in limiting pulmonary function decline in asthmatic workers and underlines the importance of allergic risk assessment and control in the management of occupational asthma.

Environmental pollution and asthma.

Clinical evidences and epidemiological studies show that allergic pathologies of the respiratory tract are increasing in the world areas with high pollution impact, demonstrating how many polluting substances favor both allergic sensitization and the bronchial inflammatory changes characteristic of asthma. It has been shown that asthma, as many other diseases, is a complex interaction between genetic predisposition and environmental stimuli that results in clinical expression of various phenotypes of asthma: allergic, intrinsic etc. Many pollutants have such a potential. Diesel exhaust particles (DEP) can favor allergic sensitization, induce acute asthma attacks and increase bronchial reactivity, acting both on allergen, on bronchial mucosa and on immune cells. In fact, DEP can favor B lymphocytes to shift to a production of IgE and T cells to produce Th2 cytokines. Asthma can be also induced by high exposure to many other substances as NO2 and first of all ozone (O3): strong oxidizing substance that is synthesized, in absence of ventilation, by photochemical reaction due to the combination of ultraviolet sun radiation on exhaust gases as NO2 and hydrocarbons. Ozone is abundant in cities with minimal concentration in the morning gradually increasing during the day until maximal levels in the afternoon and then decreasing during the night. Epidemiological studies show that the number of access to hospital for acute asthma and even the use of bronchodilator by asthmatics increase during the high level periods when Ozone constitute almost 90 percent of the total oxidants in the environment. Particulate matter of very small diameter have a crucial role in favoring asthma attacks, and smaller the substance deeper the penetration in the bronchial tree, with an inflammatory reaction in the peripheral bronchial mucosa characterized by increased vessel permeability, mucosal edema, inflammatory mediator production by damaged epithelium and inflammatory cells that determines acutely a high narrowing of the bronchial lumen and in a long period favor airways remodeling and a rapid decline of respiratory function.

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.

T regulatory cells in allergy.

The progressive understanding of the nature and mechanisms of T regulatory (Treg) cells in the last decade has changed the concept of immune tolerance, that is no longer considered as a mere lack of immune reactivity but as a finely regulated process that requires specific activity of cells, adhesion and secreted molecules. Tregs play a key role in maintenance of self-tolerance and induction of tolerance against ubiquitous innocuous non-self antigens, so preventing the onset of autoimmune diseases and allergies. This review will focus on the Treg response in allergy that is characterized by a down-regulation of allergen specific T cell proliferation and inhibition of both Th1 and Th2 cytokines production. Hence, Treg cells suppress allergen-specific Th1 and Th2 cell responses playing an important role in the physiological immune response to allergens. Further, Treg cells are able to suppress IgE production by B lymphocytes and directly or indirectly inhibit the activity of allergic inflammation effector cells, namely eosinophils, basophils and mastcells. Finally, increasing evidence suggests that Treg cells are also implicated in chronicity development of inflammatory diseases. This appears to happen through a fine interaction they entertain with resident tissue cells and has been particularly highlighted in the study of airways remodeling in asthma. The understanding of the mechanisms underlying allergen tolerance has brought new interest in the development of new allergy treatment, able to target Treg cells, both in allergy prevention and in the therapy of established allergy.

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.

Effects of palladium nanoparticles on the cytokine release from peripheral blood mononuclear cells of non-atopic women.

The object of this study is to determine the cytokine release from PBMCs exposed to Pd model nanoparticles emitted from catalytic converters. PBMCs of 8 healthy non-atopic women were incubated in the presence of Pd nanoparticles (5-10 nm) or salt (potassium hexa-chloropalladate) 10-5 and 10-6 M. Release of cytokines in supernatant of PBMCs was then determined. In cultures without LPS, IL-10 and IL-17 release from PBMCs was inhibited by Pd salt, while Pd nanoparticles inhibited TNF-alpha and IL-17 release. In LPS-stimulated cultures, release of IFN-gamma, TNF-alpha, IL-10 and IL-17 was inhibited by Pd salt, whereas IFN-gamma release was enhanced and TNF-alpha and IL-17 release was inhibited by Pd nanoparticles. In conclusion, Pd salt inhibits cytokine release, whereas Pd nanoparticles exert modulatory effects enhancing the release of IFN-gamma, a Th1 cytokine typical of delayed allergic reactions. This result is interesting considering the increase of allergic contact dermatitis to Pd in people exposed to Pd nanoparticles in urban environments.

Monomeric allergoid intragastric administration induces local and systemic tolerogenic response involving IL-10-producing CD4(+)CD25(+) T regulatory cells in mice.

The efficacy of sublingual immunotherapy, at present one of the treatments of choice for respiratory allergy, relies on the tolerance induced by oral mucosa-associated immune system; however, the gut-associated lymphoid tissue (GALT: Peyers patches and isolated lymphoid follicles) and mesenteric lymph nodes could also be involved, being stimulated by the ingested part of the allergen extract. The aim of the present study is to assess whether the exposure of the allergen exclusively to the GALT induces a tolerogenic response. For this purpose, mice were sensitized with ovalbumin or Par j 1 allergens. The corresponding gastric-resistant monomeric allergoids were then administered via orogastric gavage. After treatment, all mice were tested for: serum IgE, in vitro Th1 and Th2 cytokine release by allergen-stimulated peripheral blood lymphocytes, CD4(+)CD25(+) and CD4(+)CD25(+)IL-10(+) T cells in Peyers patches, mesenteric lymph nodes and spleen. Compared to the control, sensitized groups showed higher levels of serum IgE, lower frequency of CD4+CD25+IL-10+ T cells, at all sites, and higher amounts of in vitroreleased IL-4, IL-6 and TNF-alpha. Compared to the sensitized groups, higher frequency of CD4(+)CD25(+)IL-10(+) T cells was observed in the spleen of both Par-j 1 and OVA sensitized/treated groups and, only for ovalbumin-treated mice, in the Peyers patches and mesenteric lymph nodes, IgE and in vitro cytokines were significantly lower and equivalent to the control group. The results give the first evidence that the intragastric-restricted administration of gastric-resistant allergens restores local and peripheral tolerance in allergen-sensitized mice.

[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.

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.

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.

Respiratory allergy in agriculture.

Allergic respiratory diseases in farmers may be caused by exposures to many organic substances. Potentially inhalable particulate material of biologic origin are referred to collectively as organic dust, whose composition includes also molds and other microorganisms. Organic dust may evoke immuno-allergic reactions and cause rhinitis, asthma and extrinsic allergic alveolitis. The agricultural work environment represents a risk factor for these diseases, whose occupational origins are often overlooked by clinicians. Prevalence studies of respiratory allergic diseases among agricultural workers are advocated for the development of prevention strategies.

[Prevention of low back pain diseases in a center for the disabled]. / Prevenzione delle patologie del rachide nelle operatrici di un centro di lungo-degenza per disabili.

Our unit of occupational medicine has been asked to solve the problem of an incrising percentage of workers affected by low-back pain in a clinic for patients with handicaps. The consequence of this affections caused frequently absences at work. We organized a course for training about correct methods for moving patient not self-sufficient. The 84 workers, all female (aged 30-45), had to sign on a card all the problems they found at work and their possible solutions according to them. Then we put the cards in a box and we red each one, signing on a blackboard the problems, using a red pen and the solutions proposed, in blue. Bed organization, turnation of patient, and the difficulties in the use of lifter were the principal problems, solved trought the training course made. Then we obtained a reduction in absence at work for low-back pain of about 40% after six months since the beginning of a course of posture exercises made in the same clinic one day a week after work.

[Technical survey of safety levels established in building sites in the Pescara area]. / Indagine tecnico conoscitiva sul livello di sicurezza raggiunto nei cantieri edili della provincia di Pescara.

In 2006, in the context of the initiative aimed at "Promotion of safety and health of workers in construction yards", the Operative Unit of Occupational Health, University G. d'Annunzio, in collaboration with the Construction School of the Province of Pescara and INAIL, started a survey of construction yards around Pescara aimed at collecting data regarding respect of the specific law concerning construction yards and the risk perception of workers. The survey of 100 construction yards provided useful information towards a concise picture of safety levels obtained. In addition 300 interviews were carried out with workers to find out about their knowledge of accident prevention, how important they considered the use of personal protection devices, how often they used them, reasons for not using them, the devices most used,....and any injuries that occurred. The studied showed that, although the situation as improved compared to the past, further steps need to be taken.

[Anxiety, job stress and job insecurity among teachers with indefinite or definite time contract]. / Ansia, stress lavorativo e "job insecurity" negli insegnanti a tempo indeterminato e determinato.

Object of this study was the occupational stress of 336 teachers (276 women and 60 men) with stable or temporary employment in schools of Pescara, town of Central Italy. The levels of anxiety were determined by STAI and STAI II, those of job strain", "job insecurity" and social support by the Karasek's questionnaire, and the perception of subjective symptoms by a 12 item test. There were no significant differences depending on the type of school. The women with temporary contract showed higher levels of "job insecurity", while the men with temporary job showed also higher values of STAI I and STAI II. The scores of anxiety of the women were positively correlated with "job strain", "job insecurity" and perception of subjective symptoms and negatively with social support, while the only correlations of STAI I and STAI II of men showing statistical significance of men was that with "job insecurity. Job strain was negatively correlated with the perception of symptoms both in women and men. These results evidence differences in the occupational stress of men and women; in particular, job insecurity may enhance anxiety in men.

[Risk perception in a group of dentists from Abruzzo]. / Percezione del rischio in un gruppo di odontoiatri Abruzzesi.

Dentist's office represents an area with high infectious risk both for workers and patients. With our study we tried to analyse the relationship between dentists and prevention. We studied 104 dentists who had to answer to a questionnaire composed by 25 questions on topics such as job management, risk perception, measures adopted for prevention and knowledge about normatives regarding safety at work. From the answers we can conclude that dentists know the risk present in their work and use correctly the individual preventive dispositives; make blood control to test hepatitis markers, in particular HCV. But only 68% made HBV vaccination. Many dentists,even if they know the way of transmission of HIV, avoid to cure positive patient.

[The perception of risk in construction workers]. / La percezione del rischio negli operatori edili.

Accidents in building sites led us to study risk perception in workers employed in this field. We disposed of 300 workers, aged 18-65, who had to answer to a questionnaries were signing among seven risks the more present in their activity, chosing among five levels. So for each risk the worker had to quantify parameters such as: danger, frequence of accidents, actitude to risk-control, training on risk. The risk of falling from high sites has been perceived as extremely dangerous but it is possible to control it. Less dangerous is eyes exposition to chemical agents or dust. Manual movementation of weight and lacerations would be the most frequent source of accidents. Moreover would be insufficient the capacity to control the rick related to Weight manual movementation and vibrations. Workers answered in questionnaries that risk training on vibration was not sufficient, on the contrary they knew the risk of falling from high site. So we conclude that to reduce accidents in building sites it is necessary make better training on field, modifying the individual behavior among workers.

[Occupational stress and job insecurity in men working in a university]. / Stress lavorativo e "job insecurity" in uomini che lavorano nell'università.

77 men working in a university were investigated. Trait and state anxiety were determined by STAI I and STAI II; job strain (job demand/decision latitude), social support and job insecurity were analysed by a 46 item Karasek's questionnaire and subjective symptoms by a 12 item test. The employees of a library (mean age 49 years), in contact with students, showed significantly higher values of job strain, STAI I, STAI II and subjective symptoms than a control group of employees with similar age. Young employees and sanitary staff with temporary employment showed higher level of job insecurity than control subjects with stable position. Blood cytotoxic activity (reported in another study) was significantly lower in the old employees with job strain or in the young employees with job insecurity (but not in the sanitary staff) than in the controls; this demonstrates that not only occupational stress but also job insecurity may play an important role in affecting the health status.