Glutathione protects human airway proteins and epithelial cells from isocyanates

BACKGROUND: Glutathione (GSH), one of the major anti-oxidants of the lung, has been linked to the human response to isocyanate exposure. However, the ability of GSH to modulate key chemical reactions, thought to be central to the development of human isocyanate allergy, has not been directly analyzed under biologic exposure conditions. OBJECTIVE: To better understand the potential role of GSH in the response to occupational isocyanate exposure, we evaluated its effects on two processes thought to be involved in the development of isocyanate allergy, isocyanate-protein conjugation and epithelial cell toxicity. METHODS: The effects of GSH on (1) isocyanate conjugation with albumin, its major target in the airway fluid and (2) isocyanate-induced toxicity to human airway epithelial cell lines, A549 and NCI-H292, were tested using two different in vitro models. For protein conjugation studies, a newly described vapour exposure system was used to model the air/liquid interface at the surface of the epithelial fluid in the airways. Epithelial cell exposures were performed in fluid phase to mimic the in vivo exposure of airway cells covered by epithelial lining fluid. RESULTS: Reduced GSH prevented hexamethylene diisocyanate (HDI) conjugation to albumin in a dose-dependent manner, while oxidized GSH (GSSG) conversely increased conjugation rates. GSH levels equivalent to those found in normal human airway fluid (100 microm) provided >90% protection against HDI-protein conjugation when albumin was exposed to HDI vapour levels 10-fold above permissible occupational limits. Physiologic levels of GSH, but not GSSG, also reduced HDI toxicity to human airway epithelial cells in a dose-dependent manner, when present extracellularly, however, drugs that modulate intra-cellular GSH levels did not significantly alter isocyanate toxicity. CONCLUSIONS: Together with previously reported genetic and toxicity studies, the data suggest that airway GSH plays an important role in protection against HDI exposure and may help prevent the development of allergic sensitization and asthma.     

某公司HDI建设项目职业病危害控制效果分析

[目的]确定某公司HDI建设项目在生产过程中产生的职业病危害因素,评价职业病危害防护措施及其效果。[方法]采用职业卫生现场调查、职业卫生检测、职业健康检查和检查表分析法。[结果]该项目生产过程中产生的主要职业病危害因素HDI的STEL检测值﹤0.007～0.061mg/m3,氨的STEL检测值均﹤3.2mg/m3,氯苯的STEL检测值﹤0.07～1.0mg/m3,一氧化碳的STEL检测值﹤0.10～0.49mg/m3,光气的检测值≤0.19mg/m3,氯化氢的检测值﹤1.28～4.99mg/m3,氯气的检测值0.04～0.08mg/m3,噪声的测试结果53.5～77.7dB(A),工频电场的测试结果0.4～1.5kV/m,各种检测结果均符合GBZ2.1-2007和GBZ2.2-2007职业卫生限值要求。[结论]该项目生产过程中产生的职业病危害因素得到了有效控制。     

Immunologic cross-reactivity between different albumin-bound isocyanates

Sera of six workers with conclusive evidence for IgE-mediated sensitization to isocyanates were used for evaluation of immunologic cross-reactivities among eight different isocyanate-protein conjugates. In all cases RAST and/or skin-test investigations revealed the presence of IgE antibodies reacting specifically with HSA conjugated with those isocyanates to which workers were exposed as well as with other isocyanates with which they had not been in contact. By the RAST inhibition technique, moderate to strong mutual cross-reactivities between all tested isocyanate-HSA conjugates--even between aromatic and aliphatic ones--could be demonstrated in tests with five sera. The magnitudes of cross-reactivities differed, however, from one patient to another. One serum contained IgE antibodies that were almost completely specific to TDI-HSA; with this serum only weak cross-reactivities with other isocyanate conjugates could be demonstrated. These results indicate the predominance of closely related antigenic determinants in HSA conjugated with different isocyanates. The common antibody-binding regions are obviously recognized to different extents by antibodies of clinically sensitized workers, indicating individual differences in specificities and avidities of antibody populations. Nearly complete lack of IgE binding of ovalbumin-bound TDI in RAST and RAST inhibition indicates carrier-specific antigenicity of isocyanate-protein conjugates. In addition, since unmodified HSA did not bind IgE, antigenic determinants of the conjugates studied should be predominantly formed by the isocyanate-protein bond regions and concurrently by neighboring amino acid residues of the HSA molecule.     

Contact allergy to aliphatic polyisocyanates based on hexamethylene-1,6-diisocyanate (HDI)

Background. Aliphatic polyisocyanates based on hexamethylene 1,6‐diisocyanate (HDI) are components of lacquers, coatings, and spray paints. They are mainly composed of HDI trimers, but also contain larger oligomers, and minute amounts of HDI monomers (<1%). HDI trimers occur as biuret, isocyanurate and asymmetrical types. Objectives. We report on 4 patients with allergic contact dermatitis/contact allergy resulting from HDI‐based polyisocyanates in polyurethane paints. Methods. The patients were examined at the Finnish Institute of Occupational Health in 2000–2009. The first two patients were diagnosed by testing with their own polyurethane hardeners and ingredients of the hardeners. In 2002, HDI isocyanurate (HDI‐IC) trimer was added to our isocyanate series, and the last two patients were screened with the series. Results. Patient no. 1 was exposed and sensitized to HDI biuret trimer, patient no. 2 to HDI‐IC trimer, and patient no. 4 to HDI asymmetrical trimer. Patient no. 3 was positive with HDI‐IC trimer. He had been handling several paint hardeners containing HDI‐based polyisocyanates, but the subtypes of the trimers remained unidentified. All 4 patients were negative with HDI monomer. Conclusions. HDI trimers are novel contact allergens in workers who handle polyurethane paints. The allergic reactions cannot be explained by sensitization to HDI monomer.     

某公司HDI建设项目职业病危害控制效果评价

目的对某公司HDI建设项目在生产过程中产生的职业病危害因素进行确定，评价职业病危害防护措施及其效果。方法采用检查表法、定量分级法和综合分析相结合原则，进行定性、定量评价。结果本项目生产过程中产生的主要职业病危害因素光气的MAC检测值均〈0．07mg／m3、邻二氯苯的STEL检测值在〈0．23—2．6mg／m3之间、氯苯的STEL检测值在〈0．9—1．5mg／m3之间、氯化氢的MAC检测值均〈0．5mg／m3、工频超高压电场的检测结果在0．9—1．0kv／m之间、噪声的测试结果在48．5—72．1dB（A）之间，各种检测结果均符合GBZ1—2002和GBZ2—2002卫生标准要求。结论本项目生产过程中产生的职业病危害因素得到了有效的控制。     

Diisocyanate conjugate and immunoassay characteristics influence detection of specific antibodies in HDI-exposed workers

BACKGROUND: The structural characteristics of diisocyanate chemical protein antigens vary depending upon the methods of production, and may influence diisocyanate antigen immunoassays. The impact of different antigen preparation methods on immunoassay sensitivity, specificity, and predictive value for identifying workers with diisocyanate asthma (DA) has not been systematically evaluated. OBJECTIVE: Evaluate the influence of preparation methodology of hexamethylene diisocyanate human serum albumin (HDI-HSA) conjugates on the performance of specific antibody assays for identifying workers with confirmed HDI asthma. METHODS: Asthmatic reactions to HDI exposure were assessed in 80 autobody shop workers by specific inhalation challenge (SIC). HDI-specific IgE and IgG in serum were measured by RAST and ELISA with seven different HDI-HSA conjugates prepared in liquid phase with monomeric or polymeric HDI, or vapour-phase monomeric HDI. The HDI : HSA substitution ratios were determined by mass spectrometry. RESULTS: DA was confirmed by SIC in 23 subjects. The maximal sensitivity for detecting specific IgE among workers with positive SIC results was higher with RAST and with polymeric vs. monomeric HDI-albumin conjugates (21.7% vs. 8.7%) with a generally high specificity (>or=95%). HDI-HSA specific IgG antibody was also detected in 22-43% of HDI asthmatics depending upon the conjugate used. The specificity of specific IgG varied from 88% to 96%, and it was higher for monomeric (vs. polymeric) HDI-albumin conjugates with low (vs. high) substitution ratios. CONCLUSION: The test performance of specific IgE and IgG immunoassays for identifying a positive SIC response varied with different HDI-HSA conjugates. Standard test antigens and common immunoassays must be used to minimize inter-laboratory variability.     

Impact of ecological factors on concern and awareness about disability: A statistical analysis

The barriers that people with disabilities face around the world are not only inherent in the limitations resulting from the disability itself, but, more importantly, these barriers rest with the societal technologies of exclusion. A multiple regression analysis was conducted to examine the statistical relationship between the national level of development, the level of democratization, and the level of education of a country's population on one hand, and expressed concern for people with disabilities on another hand. The results reveal that a greater worry for the well-being of people with disabilities is correlated with a high level of country development, a decreased value of political stability and absence of violence, a decreased level of government effectiveness, and a greater level of law enforcement. There is a direct correlation between concern for people with disabilities and people's awareness about disabilities. Surprisingly, the level of education has no impact on the compassion toward people with disabilities. A comparison case for in depth illustration is discussed.     

Prediction of operative mortality based on impairment of host defense systems in patients with esophageal cancer

To determine whether operative risk based on impaired defense systems can be predicted, we examined 21 markers in 32 patients with esophageal cancer seen between 1983 and 1985 and related them to postoperative deaths. A discriminant analysis proved useful in determining whether the patient would be at risk of operative mortality, based on impaired defense systems. This model, the host defense index (HDI), was then used clinically to evaluate findings in 64 patients seen between 1986 and 1991. During this period, a change in policy for performing transthoracic esophagectomy on and perioperative care for patients with impaired defense systems was associated with a decrease in operative mortality. Thus, the HDI is beneficial to predict the risk of operative mortality based on impaired defense systems in patients with esophageal cancer. © 1993 Wiley-Liss, Inc.