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  • 1
    ISSN: 1432-0738
    Keywords: Key words Styrene ; Styrene-7 ; 8-oxide ; Human white blood cells ; 8-Hydroxy-2′-deoxyguanosine ; Oxidative DNA damage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Styrene-7,8-oxide (SO), the major in vivo metabolite of styrene, is a genotoxic compound and a potential carcinogenic hazard to occupationally exposed workers. The aim of the present work was to investigate the ability of styrene exposure to induce formation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) in white blood cells (WBC) of boatbuilders occupationally exposed to styrene. The study of these adducts was conducted to see if styrene exposure can cause oxidative damage of DNA. The 8-OHdG/105 dG ratio from 17 styrene-exposed workers showed significant increases (mean ± SD, 2.23 ± 0.54, median 2.35, P 〈 0.001) in comparison to the controls (1.52 ± 0.45, median 1.50). However, 11 out of 17 workers who were between the ages of 32 and 60 years and had been occupationally exposed to styrene for 〉10 years showed higher 8-OHdG/105 dG ratios (2.31 ± 0.62, median 2.37) in comparison to 6 workers with 〈6 years of occupational styrene-exposure (2.11 ± 0.36, median 2.05; P 〉 0.05, no significant difference between the two groups of workers). The studies presented here provide an indication that styrene exposure can result in oxidative DNA damage.
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  • 2
    ISSN: 0020-711X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0020-711X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
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  • 4
    ISSN: 0005-2787
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
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  • 5
    ISSN: 1432-1246
    Keywords: Isocyanates ; Occupational asthma ; Bronchial hyperreactivity ; Extrinsic allergic alveolitis ; Hypersensitivity pneumonitis ; Genotoxicity ; Neuropeptides ; IgE antibodies ; IgG antibodies ; Inhalative challenge test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Isocyanates are increasingly being used for manufacturing polyurethane foam, elastomers, adhesives, paints, coatings, insecticides, and many other products. At present, they are regarded as one of the main causes of occupational asthma. The large number of workers who are exposed to these chemicals have a concentration-dependent risk of developing chronic airway disorders, especially bronchial asthma. Different pathophysiologic mechanisms are involved. Immunoglobulin E (IgE)-mediated sensitization and irritative effects have been clearly demonstrated in both exposed subjects and animals. Presumably, neural inflammation due to neuropeptide release of capsaicin-sensitive afferent nerves is crucial. We collected data on 1780 isocyanate workers who had been examined by our groups. Of them 1095 (including subjects from outpatient departments) had work-related symptoms, predominantly of the respiratory tract. Specific IgE antibodies were found in 14% of the 1095 subjects. The methacholine challenge test was shown to be an inadequate predictor of the results of inhalative isocyanate provocation tests in workers and in asthmatic controls. Isocyanate (toluene diisocyanate TDI) air concentrations of 10 ppb (0.07 mg/m3) and 20 ppb (0.14 mg/m3), respectively, did not cause significant bronchial obstruction in the majority of previously unexposed asthmatics with bronchial hyperreactivity. IgG-mediated allergic alveolitis, a rare disease among isocyanate workers, was found in approximately 1 % of the symptomatic subjects. Experimental studies exhibit dose-dependent toxic effects and give evidence for tachykinin-mediated bronchial hyperreactivity after exposure to isocyanates. The clinical role of genotoxic effects of isocyanates and their by-products demonstrated here in vitro and in vivo has yet to be clarified.
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  • 6
    ISSN: 1432-1246
    Keywords: Key words Occupational asthma ; Nitric oxide ; Isocyanate ; Natural rubber latex ; Challenge test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Nitric oxide (NO) levels in the exhaled air of asthmatic patients have been shown to be increased. This observation has also been reported in workers who are allergic to laboratory animals. To determine if a challenge test with natural rubber latex (NRL) or 4,4′-diphenylmethane diisocyanate (MDI) would also produce an increase of NO exhalation in sensitized patients, we carried out this study. Methods: Nine subjects with suspected occupational asthma were exposed to MDI, and 18 took part in a challenge test with gloves powdered with NRL. Nineteen subjects underwent a challenge test with methacholine (MCh). Exhaled NO was measured by a modified chemiluminescence analyzer according to the European Respiratory Society guidelines. Results: We found that there was a decrease in exhaled NO concentrations 16–18 h after MCh challenge testing and subsequent bronchodilation with salbutamol, in three subjects. Three of nine participants had a significant immediate bronchial obstruction after exposure to MDI, of those three, two had MDI-specific IgE antibodies. After 22 h, their levels of exhaled NO had increased 〉10 parts per billion (ppb). Eight of the 18 subjects participating in the NRL challenge test displayed an NO concentration increase of at least 10 ppb after 22 h (seven had NRL-specific IgE antibodies). A significant decrease in the one-second forced expiratory volume (FEV1) was documented in four of those eight participants after NRL challenge. Conclusions: There was no clear relationship between bronchial response, substance-specific IgE antibodies and an increase in exhaled NO levels. However, there was a tendency for subjects with substance-specific IgE antibodies and bronchial reaction to develop an increase in exhaled NO concentration. Further studies are needed to determine if analysis of NO from the lower respiratory tract can become a useful non-invasive tool for detecting lower airway inflammatory response even before clinical symptoms occur.
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  • 7
    ISSN: 1432-1750
    Keywords: Acetylcholine aerosol ; Animal models ; Airway hyperresponsiveness ; Occupational lung disease ; Threshold limit value ; Toluene diisocyanate ; Rabbits ; Airway challenge test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Induction of acute lung injury and the development of airway hyperresponsiveness (AHR) by toluene diisocyanate (TDI) exposure was studied in a new rabbit model of occupational lung diseases. TDI in the range of the threshold limit value (TLV) of 10 ppb, as well as at 5 and 30 ppb, administered four times over period of 1 h to three groups of eight rabbits, did not significantly alter airway resistance (RI), dynamic elastance (Edyn), slope of inspiratory pressure generation (ΔPes/tI), arterial pressure (Pa) or aterial blood gas tensions (PaO2, PaCO2). Airway responsiveness (AR) to aerosols of 2% acetylcholine (ACH) was measured before and after each TDI exposure. After TDI inhalation of 10 ppb over 4 h, the amplitude of the ACH-induced airway constrictor response indicated by the changes in Edyn rose significantly to almost twice the control response value (p 〈 0.005). Similar changes in the amplitude of RI and in the slope of ΔPes/tI were obtained. After inhalation of 5 ppb TDI, no changes in airway reactivity were observed. The responses of respiratory mechanical parameters to ACH rose to three to four times the control responses after exposure to 30 ppb TDI. In a control group of eight animals not undergoing TDI exposure, no significant changes of respiratory responses were obtained after inhalation of 0.2% ACH for 1 min. In summary, TDI atmospheres in the range of TLV increased AR to ACH within 4 h of exposure in this rabbit model. This augmented AR may indicate an increased risk for the development of isocyanate-induced obstructive lung diseases.
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  • 8
    ISSN: 1432-1750
    Keywords: Rabbit model of occupational lung disease ; Isocyanates ; Neuropeptides ; Substance P ; Neurokinin A ; Acetylcholine ; Airway hyperresponsiveness ; Rabbits ; Tachykinin receptor antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to examine the role of neuropeptides, especially substance P (SP) and neurokinin A (NKA), in toluene diisocyanate (TDI)-induced airway hyperresponsiveness (AHR) to acetylcholine aerosols. Thirty parts per billion of TDI in air administered over 4 hours caused a significant increase in the airway constrictive response to acetylcholine (ACH) aerosols in rabbits (ΔRI: 245 ± 30%, p 〈 0.005) without altering basic values of respiratory, cardiovascular or blood gas parameters. Inhalation of the aerosolized neuropeptides SP and NKA resulted in a similar increase in airway responsiveness (AR) to ACH as exposure to 30 ppb TDI. To determine whether neuropeptides contribute to TDI-induced AHR, we studied their effects after systemic treatment with capsaicin as well as after infusion of specific synthetic antagonists for SP and NK2 (NKA) receptors. CAPS treatment performed on 4 consecutive days as well as antagonists' infusion only moderately (p 〉 0.05) decreased airway responses to ACH. CAPS application prevented the TDI-induced increase in AR to ACH in all rabbits. The increase in airway resistance to ACH did not significantly change after TDI exposure (98 ± 22% of the control response before TDI, p 〉 0.05). Simultaneous infusion of specific synthetic SP and NK2 receptor antagonists also abolished the TDI-induced increase in airway responses to ACH in all animals investigated (P 〉 0.05). The results of this study demonstrate that neuropeptides, especially the tachykinins SP and NKA, are important mediators in TDI-induced AHR in rabbits.
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  • 9
    ISSN: 1432-1750
    Keywords: Asthma ; Inflammation ; Airway hyperresponsivenessEosinophils ; Leukotrienes ; Prostaglandins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Toluene diisocyanate (TDI) is a volatile, highly reactive chemical widely used as a polymerizing agent in the production of polyurethane foams, lacquers, adhesives, and other items. Repeated airway exposures in the workplace to TDI may cause a concentration-dependent risk of developing chronic airway disorders. Different pathomechanisms are involved. IgE-mediated sensitization and irritative effects were clearly demonstrated in exposed subjects as well as in animals. In this study we examined the cellular and mediator composition in bronchoalveolar lavage fluid (BALF) of guinea pigs (eight in each group) exposed to TDI (10, 20, or 30 ppb) on 5 consecutive days for 2 hours each. Increased numbers of eosinophils and significantly elevated levels of LTB4 and LTC4/LTD4/LTE4 were obtained in BALF of all exposed animals when compared to nonexposed control animals. PGD2 and TXB2 remained unaltered in BALF. Stimulation of BALF cells of exposed and control animals with Ca-ionophore A23187 and arachidonic acid induced an increased generation of LTB4. Furthermore, BALF cells of the exposed animal groups generated immunoreactive LTC4/LTD4/LTE4, whereas controls did not show peptido-leukotriene formation in the presence and absence of stimuli. Our data clearly demonstrate an influx of eosinophils into the airways associated with mediator release and higher cellular responsiveness after TDI exposure.
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