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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.

The tripeptide Glycyl-L-prolyl-glycinamide HCl (GPG-NH2) is chosen as a model system to investigate β -turns formation in aqueous solutions and the role of trehalose in preserving this motif in drought conditions. In this first study relatively dilute solutions are investigated. Neutron diffraction experiments show the presence of both direct and water mediated β -turns, the latter ones increasing in number when trehalose is added to the aqueous solution. The structure of the ternary (GPG-NH2/water/trehalose) solution demonstrates that trehalose confines water close to the β -turns, possibly preserving their hydration when water runs low, without directly interacting with GPG-NH2 via Hydrogen bonds. Further experiments at lower water content are needed to confirm this finding.

The relationship between allergic diseases and cancer is a very controversial topic, widely discussed in the last decades. Many studies have demonstrated inverse association between allergy and cancer, but others have reached neutral conclusions or have indicated a positive role of allergy in the development of cancer. However, either inhibiting or favoring, many cells and molecules relevant in the allergic process play a role in tumorigenesis. On the one hand, activated immune cells, like classically activated macrophages "M1", activated dendritic cells, IL-33 and amphiregulin stimulated Innate Lymphoid Cells (ILC2), Th1, IFN-γ producing T CD8+ and B lymphocytes have inhibitory effects on tumorigenesis and tumor progression. On the other hand, tolerogenic immune cells, like alternatively activated macrophages "M2" (M2a, M2b and M2c), tolerogenic dendritic cells, ILC3, T regulatory and B regulatory lymphocytes, while inhibiting allergic sensitization and response, appear to favour carcinogenesis. Furthermore, M2 subtypes macrophages (M2a, M2b), IL-25 stimulated ILC2 and Th2 lymphocytes have a role both in inducing allergic reactions and in favouring cancer progression. In addition, mast cells, pivotal cells in allergy, have a different effect of tumorigenesis based on their location - they can promote cancer progression or inhibit it. Finally, eosinophils have shown a prevalent tumoricidal function mediated by α-defensins, TNF-α, granzymes A and IL-18. Better understanding the role of various cells on carcinogenesis can help in developing new strategies (diagnostic, therapeutic and of follow up) against tumor.

Living matter is a quasi-stationary out-of-equilibrium system; in this physical condition, structural fluctuations at nano- and meso-scales are needed to understand the physics behind its biological functionality. Myelin has a simple ultrastructure whose fluctuations show correlated disorder in its functional out-of-equilibrium state. However, there is no information on the relationship between this correlated disorder and the dynamics of the intrinsically disordered Myelin Basic Protein (MBP) which is expected to influence the membrane structure and overall functionality. In this work, we have investigated the role of this protein structural dynamics in the myelin ultrastructure fluctuations in and out-of-equilibrium conditions, by using synchrotron Scanning micro X Ray Diffraction and Small Angle X ray Scattering. We have induced the crossover from out-of-equilibrium functional state to in-equilibrium degeneration changing the pH far away from physiological condition. While the observed compression of the cytosolic layer thickness probes the unfolding of the P2 protein and of the cytoplasmic P0 domain (P0cyt), the intrinsic large MBP fluctuations preserve the cytosol structure also in the degraded state. Thus, the transition of myelin ultrastructure from correlated to uncorrelated disordered state, is significantly affected by the unfolding of the P2 and P0 proteins, which in this latter state do not act in synergistic manner with MBP to determine the membrane functionality.STATEMENT OF SIGNIFICANCEA better comprehension of myelin degenerative process and the role of protein dynamics in this biological membrane is a topic issue in today’s scientific community. The myelin ultrastructural fluctuations exhibit correlated disorder in its functional state, that becomes uncorrelated as it degenerates. In this work we elucidate the interplay of protein structural dynamics and myelin ultrastructure in the transition from its functional state to the degraded state. The results highlight that the intrinsically disordered Myelin Basic Protein (MBP) allows to preserve the myelin structure following both the small correlated fluctuations in physiological state and the large disordered fluctuations in degraded conditions, where the myelin functionality is close to being lost and the MBP remains the single active protein.

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.

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.

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 Environmental, behavioural and psychological stimuli can activate inflammation. Psychosocial factors such as work demands and decision latitude, social support, and psychological distress, play important roles in the development of inflammatory status. We conducted a study on occupational stress and its influence on cytokines homeostasis in Italian offshore oil installation workers. Methods Enrolled workers from an offshore oil company were divided into two groups, which took rotations of four weeks to work on the platforms at sea. The onshore and offshore groups were broadly the same in terms of their ranking, work experience, age, and distribution of job categories. All subjects complete a self- administered questionnaire collecting information on socio-demographic characteristics, occupational stress, sleep disorders, and past injuries. The salivary cortisol and serum cytokines levels were measured by ELISA, cytokines gene expression was evaluated by Real-time PCR. Results Salivary cortisol concentrations were significantly increased confirming the effectiveness of occupational stress. In fact, in our workers, cortisol level was directly correlated to job insecurity, State-Trait Anxiety (STAI-1), shift work and inversely proportional to sleep quality. In addition, we observed a direct correlation also between BMI and cortisol level. A significant increase of TNFa and a weak elevation of IL-10 level were observed in the offshore group. To examine whether changes in cytokines levels were due to changes in cell type composition, a reduction of ratio between lymphocyte percentages and neutrophils percentages (Ly/Ne%) were observed. Spontaneous expression of IL-1b, TNFa and IL-10 were higher in offshore respect to onshore workers. The increase in all PHA-induced cytokine release was significantly higher in the offshore workers. Only TNFa was significantly higher in LPS-stimulated PBMC of offshore workers. Conclusion Taken together, the current study revealed that occupational stress not only activates neuroendocrine stress systems, but also influence cytokines homeostasis.

Background Omalizumab therapy is effective and safe in patients with chronic spontaneous urticaria (CSU) resistant to nonsedating histamine 1 (H 1 ) antihistamines (nsAHs). Objective To evaluate the efficacy and safety of omalizumab in elderly (aged ≥65 years) patients with nonsedating H 1 -antihistamine–refractory CSU in a real-life setting. Methods Patients with nonsedating H 1 -antihistamine–refractory CSU (n = 322) treated with omalizumab administered every 4 weeks in doses of 300 mg for 24 weeks were divided into 2 groups according to age at omalizumab treatment onset: 15 to 64 years and 65 years or older. Treatment response was assessed using a 7-day urticaria activity score (UAS7). Adverse effects of omalizumab therapy were recorded. Results Among patients, 32 (9.9%) were 65 years or older. At baseline, CSU characteristics were generally similar among the groups, although the presence of angioedema was statistically significantly lower in patients younger than 65 years. Any differences in weekly itch severity score, hive score, and UAS7 between the 2 age groups were not significant at weeks 4, 12, and 24, with the exception of the hive score at 24 weeks and the UAS7 at week 24. No significant between-group differences were seen in the proportion of patients with a UAS7 of 6 or lower and with a UAS7 score of 0 at weeks 4, 12, 24, and 40. The proportion of patients with at least one adverse event reported as suspected to be caused by study drug was 10% in the younger group vs 6.3% in the older group ( P = .53). Conclusion Our study found that omalizumab is a well-tolerated and effective therapy for elderly patients with nonsedating H 1 -antihistamine–refractory CSU.

The use of platinum, palladium and rhodium (Platinum Group Elements - PGEs) and the possibility of exposure to their ultratrace levels is increasing. In fact, the exponential development of metallic PGE-based nanoparticles (100 nm in size) opens extraordinary perspectives in the areas of electrocatalysts and catalytic converters, magnetic nanopowders, polymer membranes, cancer therapy, coatings, plastics, nanofibres and textiles. Like other metal-based nanoparticles, exposure to PGEs nanoparticles may result in a release of ultratrace amounts of Pt, Pd, Rh ions in the body whose metabolic fate and toxicity still need to be evaluated. Furthermore, PGEs can act as allergic sensitizers by acting as haptens and inducing both type I and IV allergic reactions. In this work we studied the in vivo metabolic patterns of ultratrace levels of potent allergens and sensitizers PGE halogenated salts. (191)Pt, (103)Pd and (101m)Rh radioisotopes were prepared via cyclotron irradiation and used for radiolabelling Na2(191)PtCl4, Na2(103)PdCl4 and Na2(101m)RhCl6 salts. These anionic chlorocomplexes were intraperitoneally injected into rats (114 ng Pt kg(-1) bodyweight; 24 ng Pd kg(-1) b.w.; 16 ng Rh kg(-1) b.w.). At 16 h post-exposure, PGEs were poorly but significantly retained in all tissues analysed. Kidneys, spleen, adrenal gland, liver, pancreas and small intestine were the organs with the highest Pt, Pd, Rh concentrations. In the blood 30-35% of (103)Pd and (191)Pt and 10% of (101m)Rh were recovered in the plasma, mainly bound to albumin and to a less extent to transferrin. The hepatic and renal intracellular distribution showed the highest recovery of (191)Pt, (103)Pd and (101m)Rh in the nuclear fraction (liver) and in the cytosol (kidney). Chromatographic separation and ultrafiltration experiments on kidney and liver cytosols showed the strong ability of biochemical macromolecules to bind (191)Pt, (103)Pd and (101m)Rh, and being responsible for the retention of the three elements in the body. The link to macromolecules is the basis for the sensitizing capacity of PGEs.

We describe the case of a child affected by milk-protein induced enterocolitis, in which oral challenge with corn was performed without symptoms after a negative specific Atopy Patch Test. Food protein-induced enterocolitis syndrome (FPIES) is an uncommon nonIgE-mediated gastrointestinal food hypersensitivity of infancy, characterized by severe vomiting and diarrhea arising within 1 to 3 hours after ingestion of the causative food. Little is known about the pathophysiology of FPIES. The absence of food-specific IgE as demonstrated by negative skin prick tests suggests that the disease is not caused by an early onset IgE-mediated reaction. Atopy Patch Test has been described as sensitive and predictive in this syndrome. The hypothesis on the immunological pathogenesis has been discussed on the basis of literature data.

The hypothesis of a relationship between sarcoidosis and malignancy was firstly formulated in 1972 by Brincker. He documented an association of sarcoid reactions or sarcoidosis with 19 lymphomas and associated malignancies. Based on various epidemiological studies, for more than 20 years sarcoidosis has been considered as a condition at increased risk for cancer, particularly lymphoproliferative disorders. The existence of a sarcoidosis-lymphoma syndrome was therefore proposed, highlighting, as a potential mechanism, the uncontrolled lymphocyte proliferation and mitotic activity. A reduced ability to eliminate an antigen and chronic inflammation have been suggested as triggering events. Leading to a reduced tumor immune surveillance, a diminished myeloid dendritic cells (mDC) function, despite up-regulated co-stimulatory and maturation markers, was also raised as potential mechanism. However, some subsequent studies have questioned the presence of a close association between the two entities and have explained those previously published as the result of selection bias and misclassification. Recently, a Swedish population-based cohort study documented a significant overall excess incidence of cancer among sarcoidosis patients, especially those with multiple hospitalizations or admission in older age, emphasizing again a potential neoplastic risk. Therefore, currently, whether these patients have an increased risk of developing malignant lesions is still debated. Larger and unbiased studies are needed before drawing definite conclusions.

Sublingual immunotherapy with monomelic carbamylated allergoid (LAIS) is an effective and well tolerated treatment of respiratory allergy. The aim of the present study was to correlate the efficacy of two maintenance doses (1000 AU vs 3000 AU) of LAIS with the immunological modulation of allergen-driven Th1, Th2 and T regulatory cytokines produced in vitro by PBMCs, in patients suffering from mite allergic rhinitis. Forty-eight consecutive patients with mite allergic rhinitis were recruited. Patients were randomly assigned to group A (n=24) or group B (n=24), respectively receiving 1000 AU or 3000 AU weekly during one-year maintenance phase. Each patient was evaluated for rhinitis severity (ARIA protocol), and for drug consumption at the time of the inclusion and after 6 and 12 months of treatment. Patients were also asked to report the perceived severity of the disease and the tolerability of the treatment in a visual analogical scale (VAS). Before and at the end of the treatment allergen-driven release of cytokines by PBMCs in vitro was measured. After 1-year treatment, a statistically significant reduction of all clinical parameters was observed in all patients, associated with reduction of IL-4 and increase of INF-γ secreted in vitro by mite-challenged PBMCs. Notably, the group treated with the higher dose showed significantly better clinical and immunological results. The efficacy of LAIS is correlated to the immune modulation in a clear dose-dependent effect.

The central role of T regulatory cells in the responses against harmless environmental antigens has been confirmed by many studies. Impaired T regulatory cell function is implicated in many pathological conditions, particularly allergic diseases. The "hygiene hypothesis" suggests that infections and infestations may play a protective role for allergy, whereas environmental pollutants favor the development of allergic diseases. Developing countries suffer from a variety of infections and are also facing an increasing diffusion of environmental pollutants. In these countries allergies increase in relation to the spreading use of xenobiotics (pesticides, herbicides, pollution, etc.) with a rate similar to those of developed countries, overcoming the protective effects of infections. We review here the main mechanisms of non-self tolerance, with particular regard to relations between T regulatory cell activity, infections and infestations such as helminthiasis, and exposure to environmental xenobiotics with relevant diffusion in developing countries.

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.This study aims at evaluating the influence of allergen exposure cessation on respiratory decline in allergic asthmatic workers.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.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.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.

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: Peyer's 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. To 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 Peyer's 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 vitro-released IL-4, IL-6 and TNF-α. 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 Peyer's 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.

Some patients with nickel (Ni) allergic contact dermatitis suffer from systemic (intestinal or cutaneous) symptoms after ingestion of Ni-rich foods and experience symptoms reduction with low-Ni diet, a condition termed “systemic Ni allergy syndrome” (SNAS). We aimed at evaluating whether oral administration of low nickel doses improved clinical conditions and modulated immunological aspects of SNAS, without significant side effects. Thirty-six SNAS patients were enrolled. Treatment started after 1-month of low-Ni diet and consisted in an incremental oral NiOH dose phase (0.3ng to 1.5 μg/week) followed by a 12-months maintenance phase (1.5 μg/week). Randomly, twenty-four patients added Ni therapy to low-Ni diet and 12 remained with diet alone. All patients were allowed rescue medications (antihistamines and topical steroids). After 4 months, Ni-rich foods were gradually reintroduced. In vitro allergen-driven IL13, IL5 and IFNγ release by peripheral blood mononuclear cells was evaluated before and after treatment. Twenty-three patients receiving NiOH and the 12 control patients completed the study. Evaluation of SNAS clinical severity (by VAS and drug consumption) showed a significant difference in favor of NiOH-treated patients compared to controls. Twenty of 23 patients in the NiOH group and none in the control group tolerated Ni-rich food reintroduction. Release of all studied cytokines in culture supernatants was significantly lower after NiOH treatment. In conclusion NiOH is effective in reducing symptoms and drug consumption in SNAS and is able to modulate inflammatory parameters.

The observation of the ciliated cell dynamics by phase-contrast microscope has allowed a profound study of some parameters of the cellular components. The aim of this preliminary study is to assess the surviving time of ciliary cells using the phase-contrast microscope. Nasal cytology was carried out on 50 healthy volunteers. The ciliary beat time was assessed by a video-camera connected with a PC. The time of ciliary beat persistence was extraordinarily long (mean 210 minutes, with range 74–1260). The ciliary activity remained valid as rhythm, synchronism and metachronality. In conclusion, this preliminary study demonstrated that cilia has an energetic autonomy of great importance, able to allow a valid functional activity also in the case of partial sufferance of the cellular unit.

The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 μg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 μg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (p

Antibiotic abuse for treating rhinopharyngitis induces the occurrence of resistant bacteria. As topical drugs might reduce this phenomenon, the aims of our study are to evaluate inhaled thiamphenicol associated with acetylcysteine in children with acute bacterial rhinopharyngitis and to compare it with the use of saline solution. The trial was conducted as randomized, parallel group, and single blind. Children, aged 3–6 years, with acute bacterial rhinopharyngitis were treated with aerosolized thiamphenicol associated with acetylcysteine (250 mg: ½ vial in the morning and ½ vial in the evening) (Group A) or saline solution twice daily (Group B), both of them for 5 days. Both treatments were administered using a new device: Rinowash. The following parameters were assessed: nasal obstruction, mucopurulent rhinorrhea, post-nasal drip, cough, sore throat, fever, and cultures. Of 104 patients screened, 90 children, median age 3.7 years (44 females and 46 males), completed the study: 60 in Group A and 30 in Group B. Actively-treated children achieved a significant improvement of all parameters, but fewer than the control group. In conclusion, inhaled thiamphenicol associated with acetylcysteine may represent a valid treatment for acute bacterial rhinopharyngitis in children, as it is effective, safe, economic, and simple to use.

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.

Few cytological studies have investigated the morphologic changes occurring during lymphocyte differentiation in the nose. The aim of the study is to investigate lymphocyte and plasma cell morphology in patients with allergic rhinitis. Nasal cytology was performed in 110 patients (61 men, 49 women) of ages ranging from 12 to 47 years (mean age, 27), 72 of whom were affected by pollen allergic rhinitis (32 allergic to olive, 21 to Parietaria, 13 to grasses, and 6 to cypress) and 38 by perennial allergic rhinitis (allergy to house dust mites). Cytological samples were obtained by scraping with Rhino-Probe™. The samples were collected from the inferior middle turbinate. After fixing and drying, the samples were stained and counted. Cells belonging to the lymphocyte-plasma cell lineage were analyzed. Within this population, 5 different cellular types were identified displaying particular morphologic features of the nucleus and the cytoplasm. These morphological variants constitute various functional stages of B lymphocytes. In allergic inflammation, antigen stimulation induces B lymphocytes to differentiate and become plasma cells. The findings from this strictly morphological study will need to be confirmed by immunohistochemical and immunophenotypic studies.

Adenoidal hypertrophy (AH) is a frequent problem in children. A preliminary study evidenced that intranasal hypertonic solutions may exert an anti-inflammatory activity. The aim of the study is to evaluate the effect of intranasal hypertonic or isotonic solutions in children affected with AH. For this purpose, 78 children with AH were evaluated in a randomised and controlled study. Inclusion criteria for the study required that each patient had to have a III or IV degree of AH on the initial endoscopic examination. Children were treated with intranasal hypertonic or isotonic saline solution for 8 weeks. After treatment, endoscopy was performed to evaluate AH degree. Hypertonic treatment was associated with significant (p

Introduction: Intolerance to various foods, excluding bona fide coeliac disease and lactose intolerance, represents a growing cause of patient visits to allergy clinics. Histamine intolerance is a long-known, multifaceted clinical condition triggered by histamine-rich foods and alcohol and/or by drugs that liberate histamine or block diamine oxidase (DAO), the main enzyme involved in the metabolism of ingested histamine. Histamine limitation diets impose complex, non-standardized restrictions that may severely impact the quality of life of patients. Methods: We retrospectively evaluated 14 patients who visited allergy outpatient facilities in northern Italy with a negative diagnosis for IgE-mediated food hypersensitivity, coeliac disease, conditions related to gastric hypersecretion, and systemic nickel hypersensitivity, and who previously underwent a histamine limitation diet with benefits for their main symptoms. Serum diamine oxidase levels and the clinical response to diamine oxidase supplementation were investigated. Results: We found that 10 out of 14 patients had serum DAO activity Conclusion: In patients with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation. Properly designed, controlled studies investigating histamine intolerance that include histamine provocation are indispensable for providing insights into the area of food intolerances, which are currently primarily managed with non-scientific approaches in Italy.

Exposure to aluminum has been reported to lead to neurotoxicity. Mitochondria are important organelles involved in maintaining cell function. This study investigates the effect of aluminum on mitochondria in rat neural cells. The ultrastructure of mitochondria was observed, and the cell death rate (CDR), reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and 3-[4,5demethyl-2-thiazalyl]-2,-5diphenyl-2H-tetrazolium bromide (MTT) were measured to investigate the effect of aluminum on the mitochondrial structure and its function in neural cells. Results observed from the mitochondrial ultrastructure show that aluminum may impair the mitochondrial membrane and cristae. Increased CDR, enhanced ROS, decreased MMP, and decreased enzyme activity in mitochondria were observed in the Al-exposed neurons (100 – 500 μM). The present study demonstrates that alteration in the mitochondrial structure and function plays an important role in neurotoxic mechanisms induced by aluminum.

Data on nickel immunomodulation are contradictory. The most consistent immune effects are suppression of immune responses. It has been show that T-lymphocytes and NK cells are more susceptible to nickel toxicity than are B lymphocytes or macrophages. Data reported about cytokine production in human and nickel reactive T-cell clones are also conflicting. Some authors studied cytokine production PBMC cultures of nickel allergic individuals after stimulation with NiSo4. They showed a higher synthesis of IL4, IL5 and IL13 but not of IFN gamma and TNFα in Ni allergic subjects. We found that the addiction of NiSo4 to the PBMC cultures of non sensitised subjects induces a reduction of release of IL5, IFN γ and TNFα. Our studies demonstrate a clear difference in NK cell activity between nickel-tolerant and intolerant individuals. In particular NK cell activity in reduced in sensitised patients respect to the normal subjects and the addition of Ni to the PBMC cultures induce a significant decrease of NK cell activity. The decrease was greater in cell derived from allergic subjects than non allergic. In conclusion, reported data show Ni has immunotoxic potential. Researches are in progress in an attempt to correlate the present data with other immune parameters and to measure the effects of a Ni free diet on the immune system of subjects with Ni intolerance. The comprehension of the mechanisms inducing these changes requires further studies in the uptake and intracellular distribution and binding of the metal.

Mimosine is a non-toxic plant aminoacid which is an effective inhibitor of DNA replication by acting at the S-phase. In this study we infected mice with T. spiralis, a nematode parasite, and studied the inflammatory response through the determination of MIP-2, a C-X-C chemokine and MCP-1, a C-C chemokine in the inflamed area around the parasitic cyst. The animals were infected and their diaphragms were tested for inflammatory response. MCP-1 and MIP-2 was tested after 1, 10, 20, 30, and 40 days post inoculation, before and after mimosine treatment. The inflammatory index was calculated by counting the white blood cells around the nematode cysts, while expression of MIP-2 and MCP-1 was calculated by ELISA method and transcription by Northern blot and RT-PCR. Here we found that mimosine strongly inhibited the inflammatory index in the diaphragmatic tissue at 10, 20, 30 and 40 days post-treatment. In these experiments, mimosine had no effect on the number of cysts produced. In addition, we found that MCP-1 transcription and translation was completely inhibited by mimosine, while MIP-2 transcription and translation was partially inhibited at 30 and 40 days; yet it was totally inhibited after 10 and 20 days in encysted diaphragm tissue infected by T. spiralis. Our studies suggest that mimosine has an inhibitory effect through the inhibition of cytoplasmatic serine hydroxymethyltransferase altering the cell cycle of white blood cells. This study suggests for the first time the premise that mimosine acts as an anti-inflammatory compound.

The plant amino acid mimosine has been demonstrated to arrest cell cycle progression in the late G1-phase, and inhibits [3H] thymidine incorporation in cultured fibroblasts. In this study, 10 mice were infected with Trichinella spiralis, a nematode parasite, and treated with the antiinflammatory compound L-mimosine to determine if any alteration in the chronic inflammatory state occurred by investigating the host's immunological response. Mimosine was used at 250 μg/bolus for 25 days starting five days before the infection and continuing daily for 35 days then TNFα, IFN-γ, IL-4, IL-6, and IL-10 were determined by ELISA method, after 0, 1, 7, 14, 21, 28, 35 days post-infection, in the serum of treated or untreated animals. When animals with T. spiralis were treated with L-mimosine, inhibition of TNFα was observed within 21 days post-infection, compared with the controls (untreated mice). IFNγ was inhibited only up to the 21st day, while IL-6 was inhibited up to the 7th day post-infection and the inhibition of IL-4 was seen mainly at 21st and 35th day p.i. Mimosine-treated mice did not statistically affect the secretion of IL-10 (p > 0.05). In healthy animals, the production of cytokines were within the same limits compared with those of non-infected animals treated with L-mimosine. Our studies suggest that mimosine proved to be more effective in inhibiting TNFα and IL-6, which are mainly produced by macrophages and less effective in inhibiting IL-4, which is produced by T-cells.

The aim of the study was to assess the seasonal variability of non-specific bronchial reactivity (NSBR) evaluated with methacholine in asthmatic farmers allergic to pollens. Twenty farmers (16 male and four female) with allergy to pollens, e.g. Graminae' and Parietaria', entered the study. None of the patients had been previously treated with specific immunotherapy. Patients underwent a methacholine challenge at the first visit and then in the subsequent seasons. Four groups of tests were obtained according to the period when the challenge was performed. Group 1: challenges performed in December, January and February; group 2 in March, April and May; group 3 in June, July and August; group 4 in September, October and November. PD20 values were expressed as the natural logarithm of the cumulative dose of methacholine causing at least a 20% fall in FEV1. Bronchial hyperreactivity was highest in summer, followed by spring and autumn; in winter it was much lower. Multiple group analysis (ANOVA) showed statistically significant differences between the groups (P < 0.01). When the groups were compared individually, statistically significant differences existed only between group 1 (winter) and each of the other groups, respectively 2 (spring) (P = 0.02), 3 (summer) (P = 0.004) and 4 (autumn) (P = 0.02). The results underlined the importance of allergic inflammation in determining changes in NSBR. In the region where the study was carried out (central Italy), the grass and Parietaria pollination lasts from March to November. Therefore, farmers had a progressive increase in NSBR from spring to summer and a decrease in fall as a consequence of the varying pollen concentration in different seasons. The level of allergen exposure is, in fact, the main factor that determines the severity of bronchial inflammation, thus affecting NSBR.

The aim of the study was to assess the seasonal variability of non-specific bronchial responsiveness to methacholine in allergic asthma. One hundred sixty-five patients (83 male and 82 female) entered the study: 86 subjects (group A) with allergy exclusively to mites and 79 (group B) with concomitant allergy to pollens, e.g., "Graminae" and "Parietaria." Inclusion criteria were the absence of sensitization to other allergens, no smoking habit, withdrawal from steroids, bronchodilators, sodium cromoglycate, and antihistamines for at least four weeks before enrollment, FEV1 > 70% of the predicted value, and absence of other respiratory diseases and of upper and lower respiratory tract infections for at least one month before the methacholine challenge. None of the patients had been previously treated with specific immunotherapy. Subjects of each group (A and B) underwent methacholine challenge at first visit and were divided into four subgroups according to the period when the challenge was performed. Subgroups A1 and B1 performed the challenge in December, January, and February; subgroups A2 and B2 in March, April, and May; subgroups A3 and B3 in June, July, and August; subgroups A4 and B4 in September, October, and November. PD20 values were expressed as the natural logs of the cumulative dose of methacholine causing at least a 20% fall in FEV1. Statistical analysis was carried out using multiple group analysis and Student's t-test. Results showed that the highest non-specific bronchial responsiveness was observed in autumn (ln PC20 = 4.54 +/- 1.51) in patients allergic to mites only (group A), and in summer (ln PC20 = 4.72 +/- 2.11) in those of group B. Multiple group analysis showed statistical significant differences between subgroups within each group (group A, p = 0.039; group B, p < 0.001). In patients allergic exclusively to house dust mites (group A), multiple comparisons and Student's t-test showed statistically significant differences between non-specific bronchial responsiveness (NSBR) assessed in autumn and those of other seasons (winter, p = 0.002; spring, p < 0.001; summer, p = 0.082). These results confirm that the level of allergen exposure may influence NSBR. Mite-allergic patients showed an increase of NSBR in autumn, possibly as a consequence of higher indoor mite concentration. However, mite- and grass-allergic patients had wider variations of NSBR, possibly reflecting changes in seasonal pollen concentration.

Background: This study correlates biomarkers of atopy (serum total and specific IgE) and inflammation (serum eosinophil cationic protein) with bronchial hyperreactivity assessed after the complete end of pollination, in a group of farmers suffering from grass-allergic asthma. Methods: A total of 28 asthmatic farmers, with allergy to grass pollen, reporting persistent asthma symptoms after grass pollination, were enrolled. An accurate allergologic screening excluded other sensitizations. Analysis of total and grass-specific IgE and eosinophil cationic protein was carried out before (March) and during (May) the following spring. After the complete end of pollination, bronchial hyperreactivity was assessed. Results: Symptoms (cough, wheezing) persisted during the autumn for a mean period of 41 days (range 13-69). Total IgE was moderately high and grass-specific IgE ranged from 9.25 to 41.12 kU/l without significant differences before and during spring. On the contrary, serum ECP levels significantly increased during the pollination period. PD 20 methacholine evaluated after the end of grass pollination was negatively significantly correlated with levels of total IgE (r = -0.73; P < 0.01) and the increase (from March to May) of serum ECP (r = -0.75; P < 0.01). However, PD 20 methacholine did not correlate with grass-specific IgE and serum ECP absolute values of both March and May. A positive correlation was found between number of postseasonal days with symptoms and both spring increase of serum ECP (r = 0.75; P = 0.04) and levels of total IgE (r = 0.76; P < 0.01). The number of postseasonal days with symptoms inversely correlated with postseason PD 20 methacholine (r = -0.76; P < 0.01). Conclusions: The study demonstrates that in grass-sensitized farmers with asthmatic symptoms persisting for several weeks after grass pollination has ceased, the degree of airways hyperreactivity and the duration of postseasonal symptoms are directly related to the spring increase of ECP levels, as well as to the level of total IgE in serum. This allows us to identify two candidate biomarkers for the risk of developing prolonged asthma symptoms, and for the effective monitoring of anti-inflammatory treatment and allergen-specific immunotherapy.

This study investigates lymphocyte subsets in both the gastrointestinal mucosa and blood, in patients with nickel allergic contact dermatitis, after 10 mg oral nickel challenge (double-blind, placebo-controlled). 6 such patients with cutaneous symptoms induced only by skin contact with nickel (group A), 6 with a flare-up of cutaneous symptoms after food nickel ingestion (group B) and 6 healthy controls (group C) were enrolled. Blood lymphocyte subsets (CD4, CD45RO, CD8) were analyzed before and after 4 and 24 h from the challenge (test 1, 2, and 3), and intestinal biopsies were performed 2 days later. Challenges were positive in group B and negative in group A and controls. Serum and urine nickel levels significantly increased after nickel ingestion, with no differences between the 3 groups. At test 3, a significant decrease of the all CDs studied was found in group B. Biopsies of this group showed higher levels of CD45RO+ cells in the lamina propria and in the epithelium and lower levels of epithelial CD8+ lymphocytes. This study confirms that ingested nickel may induce flare-up of cutaneous reactions in some nickel-allergic patients, independently of the degree of sensitization and the intake of metal. In these patients, oral nickel stimulates the immune system, inducing maturation of T lymphocytes from virgin into memory cells; these latter cells seem to accumulate in the intestinal mucosa. The immunoreaction also involves CD8+ cells, whose role is not yet clear.

This study evaluates the immune response to exposure to an urban environment from 30 non-atopic and 30 non-symptomatic women with history of respiratory and/or cutaneous allergies. Blood lymphocyte subsets and serum interleukin (IL) 4 and interferon gamma (INF-gamma) of the two groups were similar, while serum IgE and "in vitro" production of IL-4 and INF-gamma by mononuclear blood cells of the atopic women were higher spontaneously or in the presence of PHA, respectively. Blood lead of the nonatopic women (mean 55 microg/l) was positively correlated with CD4+-CD45RO-, CD3+-CD8+ and CD3--HLA-DR+ lymphocyte subsets, while urinary trans-trans muconic acid (a metabolite of benzene) of both groups of women (mean about 50 microg/l) was significantly correlated with NK CD16+CD56+ lymphocytes. Urine chromium of the non-atopic subjects was significantly correlated with activated T, B and NK HLA-DR+ cells. Urine nickel of both groups of women was correlated with CD4+-CD45RO+ "memory" lymphocytes and their ratio with CD4+-CD45RO- "virgin" lymphocytes suggesting that the metal enhances maturation of "virgin" into "memory" lymphocytes. On the whole, this study demonstrates that exposure to low levels of toxic agents, produced by vehicular traffic in an urban environment, exerts effects on immune functions of women.

This study evaluates the immune response to ingestion of 10 mg of nickel (Ni) (as Ni sulphate) in 19 young non-atopic Ni-sensitised or 9 non-allergic women (group A). After Ni ingestion at 8 a.m, non-allergic and 12 Ni-sensitised women (group B) were non-symptomatic, while 7 Ni-sensitised women (group C) showed a flare up of urticaria and/or eczema. Serum and urine Ni were greatly lower before Ni administration than after 4 and 24 hours, without difference among the 3 groups. Before treatment, group B and C showed higher values of blood CD19+ and CD5--CD19+ cells than group A, while group C showed higher serum interleukin (IL) 2 and lower serum IL-5. Four hours after Ni ingestion, group C showed significant increase in serum IL-5. Twenty-four hours after treatment, group A showed a significant reduction in blood CD4+-CD45RO- "virgin" cells and an increase of CD8+ lymphocytes, while group C showed a marked decrease in total blood lymphocytes and CD3+, CD4+-CD45RO-, CD4+-CD45RO+, CD8+, CD19+ and CD5--CD19+ cell subsets. These data may be explained with migration of lymphocytes in tissues with a Th0-like immune response, as shown by the elevated serum IL-2 and the increase of serum IL-5 during the test.

The aim of this study was to investigate the effect of pyridoxine (Vitamin B6) deficiency on the immunological response of BALB/c mice infected with the parasite T. spiralis. Specific anti-parasite IgM and IgG immunoglobulins were detected by ELISA method in the serum of treated animals at different periods for 60 days post infection. Vitamin B6-deficiency was induced in two separate groups of mice by either (1) maintaining the mice on a Vitamin B6-deficient synthetic pellet diet for 40 days before infection, or (2) by daily intraperitoneal injection of 8 x 10(5) M/100 microl of 4-Deoxypyridoxine (4-DPD), a potent antagonist of Vitamin B6 for 20 days prior to infection. These two groups of mice were then injected with 100 larvae (L1-T. spiralis) per os. Parasite burdens in the mice were observed by light microscopy. Cysts were present in the diaphragms of the mice after 60 days post-infection. Parasite specific IgG, as well as IgG1 levels were determined in the sera of infected mice fed a normal diet. These levels were found to be lower in the 4-DPD-treated mice compared to the untreated mice. The inhibition started from the 10th day and continued to the 60th day, and in the 4-DPD-treated group the inhibition initiated after 24 h to 60 days. IgM level also was depressed by 4-DPD, starting from 24 h after injection of the compound. In mice fed Vitamin B6-deficient diets the levels of IgG were lower than in mice fed normal diets. These results show that BALB/c mice infected with T. spiralis and fed either a Vitamin B6-deficient diet or a diet which included the Vitamin B6-antagonist, 4-DPD, both influence the course of IgG, IgG1 and IgM production.

In this study, 20 non-allergic and 20 non-atopic women sensitised only to nickel (Ni) showed similar levels of urine and serum Ni and serum chromium (Cr). On the contrary, serum copper, a marker of inflammation, was significantly higher in the Ni-sensitised group. Sensitised women also had higher values of blood B CD19+, CD5--CD19+ and B and natural killer CD3--CD25+ lymphocytes, but not alterations of some other lymphocyte subsets and serum cytokines. Urine Ni was correlated with "memory" CD4+-CD45RO+ lymphocytes in the non-allergic women and with T CD4+-CD45RO+ and CD3+-CD25+ cells in the atopic women; these subjects also showed a statistically significant correlation of serum Ni with B CD5+-CD19+ lymphocytes and serum IL-13. Moreover, serum Cr of both groups of women was positively or negatively correlated with activated HLA-DR+ cells and/or serum IL-5 and interferon gamma. These results (confirming in part those of a previous study on non-allergic men) suggest that both Ni and Cr are involved in mechanisms regulating the immune response and that allergy to these metals could be considered an alteration of their physiological role.

MCP-1 is a small (8-10 KDa) protein and a prototype member of the CC chemokine β subfamily, which plays a critical role in acute and chronic inflammation. Recent evidence suggests an important role for MCP-1, MCP-2 and MCP-3 in a number of pathological states, including delayed type hypersensitivity conditions, parasitic infections and rheumatoid arthritis. Forty BALB-c mice were treated with the parasite Trichinella spiralis. After the infection the animals were sacrificed at different periods from the initial infection and MCP-1 and TNFα were quantified in the mouse serum. The level of MCP-1 in the serum of mice infected with 100 larvae increase 27.5 ± 7.0 pg/ml at day 23, to a maximum level of 31.5 ± 5.0 pg/ml at day 33, from then decreased to 14.6 ± 2.0 pg/ml at day 47. When the mice were infected with 200 larvae of T. spiralis the maximum increase was 34.4 ± 2.5 pg/ml found on day 23. From day 33 to day 47 MCP-1 levels were decreased. In addition, in infected mice levels of TNFα were detectable in the serum as early as day 1. The level of TNFα was maximum at day 35 (3812 ± 224 pg/ml). Serum from non-infected mice contained no detectable levels of either MCP-1 or TNFα. However, even if MCP-1 seems to be implicated in Trichinellosis, its exact role and function in inflammatory parasitic diseases remains to be determined.

15 women with a positive patch test only to nickel (Ni) and without atopy and 10 control women were selected for the study. Blood and urine specimens were collected with a standard procedure either before (at 8 a.m.) or 4 and 24 h after the ingestion of 10 mg of Ni (as Ni sulfate). 7 of the Ni-sensitized patients showed a flare-up of eczema and/or urticaria during the test, while the other women were non-symptomatic. Serum and urine Ni of controls and Ni-sensitized women did not significantly differ. Serum and urine Ni levels determined before the oral Ni challenge were in the range of reference values recently reported by other authors (0.2-2.0 micrograms/l of serum or urine). Ni was greatly augmented in urine and serum 4 h after the challenge (25th-75th percentiles: 43-264 micrograms/l urine Ni and 15-52 micrograms/l serum Ni). 24 h after Ni ingestion, urine Ni was 41-153 micrograms/l and serum Ni 4-17 micrograms/l. Our study confirms a previous investigation showing similar levels of serum and urine Ni following ingestion of the metal in control and Ni-sensitized women without atopy.

Allergic rhinitis (AR) may significantly impair quality of life (QoL), and therefore it is important to evaluate the effectiveness of the available treatments on such a parameter. We studied QoL by a real-life model in a large group of patients with rhinitis caused by the most common aeroallergens and assessed the effects of high-dose sublingual immunotherapy (SLIT). An overall number of 452 subjects (229 males, 223 females, mean age 25 ± 13 years) was included in the study. Of them, 208 were allergic to house dust mites, 196 to grass pollen, 104 to Parietaria pollen, 48 to olive pollen, 28 to ragweed pollen, and two to cypress pollen. QoL was measured before and after SLIT with the specific questionnaire Rhinoconjunctivitis Quality-of Life-Questionnaire (RQLQ) introduced and validated by Juniper. At the same time, patients evaluated their clinical status by visual analogue scale (VAS) from 0 (worst) to 10 (best). SLIT was performed by extracts from Stallergenes standardized in index of reactivity (IR) by a build-up phase in 11 days and a maintenance phase with 300 IR three times a week for the duration of the study. All side-effects were registered. The mean RQLQ was 2.93 ± 1.04 before SLIT and 1.50 ± 0.98 after SLIT (P < 0.001), with comparable improvement in the different allergen treatments. The respective mean VAS score was 4.47 ± 2.11 and 6.92 ± 1.64 (P < 0.001). SLIT was completely tolerated in 395 patients (87.4%), while in 57 (12.6%) it gave rise to slight reactions, mostly at the local level in the mouth or in the gastrointestinal tract. High dose SLIT, administered in a clinical model comparable with routine application, provides significant improvement of both clinical status and QoL in patients with AR caused by common aeroallergens.

Regulated upon activation normal T expressed and secreted (RANTES) is a new inducible protein member of the human C-C branch of chemokines. RANTES is a potent monocyte and lymphocyte chemoattractant and is a mediator of inflammatory responses. In these studies we found that RANTES 10 ng/50 microl chemoattracts basophilic cells in a dose-dependent manner 4 h after an intradermal injection in rat skin sites, as revealed by optic microscopy. Moreover, in biopsy specimens from rat skin injection sites histamine release was significantly higher (P < 0.05) than in controls (PBS 50 microl) after 4 h from RANTES treatment. The presence of basophilic cells in rat skin injection sites after RANTES-treatment was also confirmed by electron microscopy studies. In addition, histidine decarboxylase (HDC) mRNA was increased in rat skin sites injected with RANTES compared to sites injected with PBS (controls). Our report describes additional biological activities for RANTES, suggesting that this human chemoattractant protein may play a fundamental role in histamine and HDC generation, along with basophilic cell recruitment.