Dermatomyositis and MIG.

Several studies demonstrated the presence of an elevated expression of chemokine (C-X-C motif) ligand (CXCL)9/monokine induced by interferon (IFN)-γ (MIG) on macrophages and in T cells in perimysial infiltrates of patients with dermatomyositis (DM), and of chemokine (C-X-C motif) receptor (CXCR)3 expression on the majority of T cells in the same patients. This underlines the importance of T helper 1-mediated immunity, and in particular the MIG/CXCR3 interaction, in the immunopathogenesis of DM. The importance of MIG has been confirmed by a study on patients with DM about the presence of chemokines and their receptors in infiltrating cells at the level of lesional skin. This study showed that type I IFN chemokines, in particular MIG, are firmly related with the active disease and its clinical score in juvenile DM, suggesting the importance of chemokines trend in monitoring disease activity and in the treatment indication.

Sarcoidosis and the Th1 chemokine MIG.

Sarcoidosis is a systemic inflammatory disease, affecting any organ, and that can be discovered by accident in approximately 5% of cases. High levels of the type-1 helper (Th1)-dependent chemokine, monokine induced by interferon (IFN)-γ (MIG)/chemokine (C-X-C motif) ligand (CXCL)9, and its receptor CXCR3 have been reported in bronchoalveolar lavage and biopsy samples of patients with sarcoidosis. These elevated levels are related with the amount of CD4+ lymphocytes and total lymphocytes. Alveolar macrophages resulted stained positive for all CXCR3 ligands and produced elevated levels of these chemokines. It has been shown that the epithelioid and giant cells of the sarcoid lungs were stained positive for MIG, IFN-inducible T-cell α chemoattractant (I-TAC) and IFN-γ-inducible protein 10 (IP-10), suggesting that MIG plays an important role in the accumulation of Th1 lymphocytes in sarcoid lungs. In addition, serum levels of MIG were related with the severity of the disease, and a correlation between the serial measurements of MIG and the clinical course of the disease was shown, indicating MIG as a potentially useful biomarker of sarcoidosis and its severity.

MIG chemokine in systemic sclerosis. MIG in Systemic sclerosis.

Several studies have proposed in Systemic sclerosis (SSc) patients that the monokine induced by interferon (IFN)-γ(MIG)/chemokine receptor (CXCR)3 axis has a determinant role in the autoimmune process and in fibrosis. Elevated MIG levels were linked to a more severe clinical phenotype, with kidney, lung and thyroid involvement. Then MIG could be considered a marker of a more aggressive autoimmune process. In vitro, SSc fibroblasts have different kinds of dysregulation in the secretion of MIG, once treated with cytokines (as interferons). Moreover, MIG has been suggested as a serologic marker of a more severe SSc form, so it could be useful for the risk stratification of SSc patients.

CXCL8 and CXCL11 chemokine secretion in dermal fibroblasts is differentially modulated by vanadium pentoxide.

An increase in skin rashes or atopic dermatitis has been observed in individuals working with vanadium. However, to the best of our knowledge no in vivo or in vitro studies have evaluated the effect of exposure to vanadium in dermal fibroblasts. Cells viability and proliferation were assessed by WST­1 assay, cells were treated with increasing concentrations of V2O5 (1, 10 and 100 nM). CXCL8 and CXCL11 concentrations were measured in the supernatants using an ELISA assay. V2O5 was not observed as having a significant effect on dermal fibroblast's viability and proliferation. However, it was revealed that V2O5 was able to induce the secretion of CXCL8 and CXCL11 chemokines into dermal fibroblasts. V2O5 synergistically increased the effect of interferon (IFN)γ on CXCL11 secretion. In addition, V2O5 synergistically increased the effect of the tumor necrosis factor α on CXCL8 secretion and abolished the inhibitory effect of IFNγ. V2O5 induction of CXCL8 and CXCL11 chemokines may lead to the appearance and perpetuation of an inflammatory reaction into the dermal tissue. Further studies are required to evaluate dermal integrity and manifestations in subjects occupationally exposed, or living in polluted areas.

Induction of Th1 chemokine secretion in dermal fibroblasts by vanadium pentoxide.

Vanadium is a soft, silvery­grey metal with a number of different oxidation states. The most common commercial form of vanadium is vanadium pentoxide (V2O5). All vanadium compounds are considered toxic. An increase in skin rashes has been observed in certain vanadium workers, including the development of atopic dermatitis. However, to the best of our knowledge, no prior in vivo or in vitro studies have evaluated the effect of vanadium exposure in human dermal fibroblasts. The present study evaluated the effect of V2O5 on proliferation and chemokine secretion in dermal fibroblasts. The results revealed that V2O5 had no significant effect on the viability or proliferation of fibroblasts, however it was able to induce the secretion of T­helper (Th)1 chemokines from dermal fibroblasts, synergistically increasing the effect of important Th1 cytokines, including interferon­Î³ and tumor necrosis factor­α. Through these processes, V2O5 may lead to the induction and perpetuation of an inflammatory reaction in dermal tissue. The induction and perpetuation of inflammation in the dermis and the variety of involved candidate genes may be at the base of V2O5­induced effects following occupational and environmental exposures. Further studies are necessary to evaluate dermal integrity and manifestations in subjects who are occupationally exposed, or living in polluted areas.

Vanadium pentoxide induces the secretion of CXCL9 and CXCL10 chemokines in thyroid cells.

Vanadium is a grey metal, existing in different states of oxidation, whose most common form in commercial products is vanadium pentoxide (V2O5). All vanadium compounds have been considered toxic. A carcinogenic role of vanadium on the thyroid has recently been proposed. However no in vivo or in vitro studies have evaluated thyroid disruption in humans and/or animals after exposure to vanadium. In the present study we evaluate the effect of V2O5 on proliferation, and chemokine secretion in normal thyrocytes. Our study demonstrated that V2O5 has no effect on thyroid follicular cell viability or proliferation, but it is able to induce the secretion of T-helper (Th)1 chemokines into the thyroid, synergistically increasing the effect of important Th1 cytokines such as interferon (IFN)γ and tumor necrosis factor (TNF)α. Through this process, V2O5 promotes the induction and perpetuation of an inflammatory reaction in the thyroid. Further studies are necessary to evaluate thyroid function, and nodules, in subjects occupationally exposed, or living in polluted areas.

IP-10 in occupational asthma: review of the literature and case-control study.

OBJECTIVES: T-helper (Th)2 cytokines are thought to mediate most of the allergic inflammatory responses associated with atopic asthma. But the Th1-related chemokine, interferon (IFN)-γ-induced protein 10 (IP-10)/chemokine (C-X-C motif) ligand (CXCL)10, was the predominant chemokine measured during human allergic pulmonary late-phase reaction. Viral infection and allergens can exacerbate asthma by inducing the accumulation of these chemokines and inflammatory cells in the airway. Short-acting ß2-adrenoreceptor agonists, budesonide and formoterol (all important relievers in asthma exacerbation), such as vitamin D3, vitamin C, have been shown to inhibit airway cells inflammatory responses by modulating these chemokines. Furthemore it has been suggested that Th1-related IP-10 and monokine induced by IFN-γ (MIG)/CXCL9 may be useful inflammatory markers of asthma exacerbation. PATIENTS AND METHODS: In this study we have evaluated serum levels of the Th1-related CXC chemokine IP-10, in 8 patients with occupational asthma (OA) during exacerbation due to occupational exposure, and after 2-3 months, when patients were in stable conditions, in comparison with 8 age and gender matched healthy subjects. RESULTS: A significant increase in the serum levels of IP-10 were found in OA patients with an acute exacerbation in contrast to healthy controls (p<0.01), and in comparison with same OA patients after 2-3 months, when they were without any respiratory symptoms or disorders. CONCLUSIONS: These results suggest that the Th1-related CXC chemokines IP-10 is an useful inflammatory marker of OA exacerbation. However, other studies in larger number of patients are needed.

Mesothelioma and interferon-γ-dependent chemokine IP-10.

Recently it has been shown that interferon (IFN)-γ plays an important role in mesothelioma, mediated by the main IFN-γ dependent chemokines, chemokine (C-X-C motif) ligand (CXCL)10/IFN-γ- induced protein 10 (IP-10). IP-10 is up-regulated in malignant mesothelioma (MM), suggesting a relationship with development of these tumors. Nanoparticles containing nickel, that increase the risk for pleural diseases, induced increased levels of IP-10 in rat pleural mesothelial cells. Chemokine (C-X-C motif) receptor (CXCR)3 expression in CD4(+) T cells from pleural plaques and MMs was significantly decreased compared with that from healthy donors suggesting that CXCR3, IFN-γ, and IP-10 may be candidates to detect and monitor disease status. In a patient with asbestos-related malignant pleural mesothelioma the oncolytic adenovirus (ONCOS-102) induced prominent infiltration of CD8(+) lymphocytes to tumor, marked induction of systemic antitumor CD8(+) T-cells and expression of IP-10. Furthermore, increased IP- 10 concentrations were observed in the sera of the asbestos-exposed workers and were associated with the severity of asbestos-related diseases. These findings suggest that IP-10 chemokine may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by nonmalignant asbestos-related diseases.

SWAT meta-modeling as support of the management scenario analysis in large watersheds.

In the last two decades, numerous models and modeling techniques have been developed to simulate nonpoint source pollution effects. Most models simulate the hydrological, chemical, and physical processes involved in the entrainment and transport of sediment, nutrients, and pesticides. Very often these models require a distributed modeling approach and are limited in scope by the requirement of homogeneity and by the need to manipulate extensive data sets. Physically based models are extensively used in this field as a decision support for managing the nonpoint source emissions. A common characteristic of this type of model is a demanding input of several state variables that makes the calibration and effort-costing in implementing any simulation scenario more difficult. In this study the USDA Soil and Water Assessment Tool (SWAT) was used to model the Venice Lagoon Watershed (VLW), Northern Italy. A Multi-Layer Perceptron (MLP) network was trained on SWAT simulations and used as a meta-model for scenario analysis. The MLP meta-model was successfully trained and showed an overall accuracy higher than 70% both on the training and on the evaluation set, allowing a significant simplification in conducting scenario analysis.

Th1 chemokines in ulcerative colitis.

Many studies have shown that chemokine (C-X-C motif) receptor (CXCR)3 (a chemokine receptor in the CXC family) and its ligand chemokines, monokine induced by interferon (IFN)-γ(MIG), IFN-γ-inducible protein 10 (IP-10) and IFN-inducible T-cell α chemoattractant (I-TAC), are strongly overexpressed in the intestinal mucosa of mice with experimental colitis, and in patients with ulcerative colitis (UC) both in lymphocytes, in macrophages and in epithelial cells. IFN-γ induces CXCR3 and its chemokines expression in epithelial colonic cells; MIG, IP-10 and I-TAC are important for the recruitment of granulocytes and mononuclear cells and thus for the maintenance of inflammation in UC. Serum IP-10 levels reflected UC disease activity, and it may be a marker for the responsiveness of patients to treatments. Recently, a phase II study suggested that an anti-IP-10 antibody, BMS-936557, is a potentially effective therapy for moderately-to-severely active UC.

Sarcoidosis and Th1 chemokines.

Many studies have shown high levels of the chemokine Interferon-γ-inducible protein 10 (IP-10) and its chemokine (C-X-C motif) receptor (CXCR) 3, expressed on Type-1 helper (Th1) lymphocytes, in bronchoalveolar lavage (BAL) and biopsy samples of patients with sarcoidosis. The levels of IP-10 and the other CXCR3 ligands, Monokine induced by IFN-γ (MIG) and Interferon-inducible T-cell α chemoattractant (I-TAC), in bronchoalveolar lavage fluid (BALF) were correlated with the numbers of both total and CD4(+) lymphocytes. Alveolar macrophages were stained positive for all CXCR3 ligands and produced increased amounts of these chemokines. This positive staining was also observed in the epithelioid and giant cells in the sarcoid lungs. These findings suggest that IP-10, MIG and I-TAC play important roles in the accumulation of Th1 lymphocytes in sarcoid lungs. Furthermore, it has been demonstrated that circulating IP-10 levels correlated with measures of disease severity in sarcoidosis, and that its serial measurements corresponded to the clinical course of the disease, suggesting that IP-10 is a potentially useful biomarker of sarcoidosis and its severity.

[Safety and health protection of professional divers in the context of the European Diver Technology Committee (EDTC): technical training and diver competence, role of the "examining" physician]. / La sicurezza e la tutela della salute dell'operatore subacqueo professionale nel contesto del Comitato Europeo di Tecnologia Subacquea (EDTC): formazione tecnica e competenza del sommozzatore, ruolo del medico "esaminatore".

It is necessary to standardize some parameters for occupational health and safety of their professional diver: risk assessment of work duty, appropriate training program and sanitary surveillance. European Diver Technology Committee (EDCT) gathers the member State's experience about safety procedures, professionals and sanitay surveillance. EDTC criterions to whom it is possible to refer in Italy waiting specific regulations are reported.

Nonfatal systemic reactions to subcutaneous immunotherapy: a 10-year experience.

The present retrospective study reviews our clinical experience with Subcutaneous immunotherapy (SIT) over a 10 year period (1981-1991), in order to assess both incidence and clinical features of nonfatal systemic reactions due to this treatment. 192,505 injections were globally administered to 2,206 outpatients, following the suggested precautionary guidelines. We observed 115 systemic reactions (5.2% of patients and 0.06% of injections) and no fatalities. The association asthma + urticaria was the most frequent reaction (67%), followed by asthma alone (22%). No risk factor related to age, gender, pollen season or manufacturer was observed. The occurrence of systemic reactions was highly frequent in asthmatic patients, but approximately 1/3 of the patients who presented reactions had never previously suffered from asthma. The largest part of the observed reactions occurred during the maintenance phase of treatment. Almost all adverse events occurred within 30 minutes after the injection and they were promptly controlled by routine therapy. We conclude that subcutaneous immunotherapy, if performed with careful compliance to good clinical practice rules, is a safe treatment for respiratory allergy.

Disopyramide determination by gas chromatography, liquid chromatography, and gas chromatography--mass spectrometry.

Disopyramide is determined in serum by gas chromatography with a nitrogen-selective detector, by liquid chromatography, and by gas chromatography--mass spectrometry. Comparable results are obtained with the three techniques, with a within-run and between-run precision of 5 to 10% (coefficient of variation). Least-squares analysis of data on patients' sera, analyzed first by gas chromatography (y) and then liquid chromatography (x), gave a slope of 1.12; y-intercept, -0.31; standard error of estimate, 0.46; and correlation coefficient, 0.94. Comparison of patients' sera by gas chromatography (y) and then by gas chromatography--mass spectrometry (x) gave a slope of 0.94; y-intercept, 0.42; standard error of estimate, 0.38; and correlation coefficient, 0.97. Interferences observed when using one technique--for example, gas chromatography--can be eliminated by analyzing the sample extract with one of the other techniques.