| 1. |
- Bengtsson, Anders A., et al.
(författare)
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Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren’s Syndrome and Systemic Sclerosis
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Clinically, SLE is a heterogeneous disease and shares features of several other rheumatic diseases, in particular primary Sjögrens syndrome (pSS) and systemic sclerosis (SSc), why it is difficult to diag- nose The pathogenesis of SLE is not completely understood, partly due to the heterogeneity of the disease. This study demonstrates that metabolomics can be used as a tool for improved diagnosis of SLE compared to other similar autoimmune diseases. We observed differences in metabolic profiles with a classification specificity above 67% in the comparison of SLE with pSS, SSc and a matched group of healthy individuals. Selected metabolites were also significantly different between studied diseases. Biochemical pathway analysis was conducted to gain understanding of underlying pathways involved in the SLE pathogenesis. We found an increased oxidative activity in SLE, supported by increased xanthine oxidase activity and an increased turnover in the urea cycle. The most discriminatory metabolite observed was tryptophan, with decreased levels in SLE patients compared to control groups. Changes of tryptophan levels were related to changes in the activity of the aromatic amino acid decarboxylase (AADC) and/or to activation of the kynurenine pathway.
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| 2. |
- Madsen, Rasmus Kirkegaard, 1979-, et al.
(författare)
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Diagnostic properties of metabolic perturbations in rheumatoid arthritis
- 2011
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 13:1, s. R19-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of the study was to assess the feasibility of diagnosing early rheumatoid arthritis (RA) by measuring selected metabolic biomarkers. METHODS: We compared the metabolic profile of patients with RA with those of healthy controls and patients with psoriatic arthritis (PsoA). The metabolites were measured using two different chromatography-mass spectrometry platforms, thereby giving a broad overview of serum metabolites. The metabolic profiles of patient and control groups were compared using multivariate statistical analysis. The findings were validated in a follow-up study of RA patients and healthy volunteers. RESULTS: RA patients were diagnosed with a sensitivity of 93 % and a specificity of 70 % in a validation study using detection of 52 metabolites. Patients with RA or PsoA could be distinguished with a sensitivity of 90 % and a specificity of 94 %. Glyceric acid, D-ribofuranoise and hypoxanthine were increased in RA patients, whereas histidine, threonic acid, methionine, cholesterol, asparagine and threonine were all decreased when compared with healthy controls. CONCLUSIONS: Metabolite profiling (metabolomics) is a potentially useful technique for diagnosing RA. The predictive value was irrespective of the presence of antibodies against cyclic citrullinated peptides (ACPA).
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| 3. |
- Broberg Palmgren, Karin, et al.
(författare)
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The GSTP1 Ile105 Val polymorphism modifies the metabolism of toluene di-isocyanate.
- 2010
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Ingår i: Pharmacogenetics & Genomics. - 1744-6872 .- 1744-6880. ; 20:2, s. 104-111
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Toluene di-isocyanate (TDI) is widely used in the production of polyurethane foams and paints. As TDI causes respiratory disease in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Polymorphisms in TDI metabolising genes may affect elimination kinetics, resulting in differences in body retention, and in its turn differences in adverse effects. OBJECTIVES: To analyze how genotype modifies the associations between (i) TDI in air (2,4-TDI and 2,6-TDI) and its metabolites toluene diamine (TDA; 2,4-TDA and 2,6-TDA) in hydrolyzed urine; and (ii) 2,4-TDA and 2,6-TDA in hydrolyzed plasma and 2,4-TDA and 2,6-TDA in urine. METHODS: Workers exposed to TDI were analyzed for 2,4-TDI and 2,6-TDI in air (N=70), 2,4-TDA and 2,6-TDA in hydrolyzed urine (N=124) and in plasma (N=128), and genotype: CYP1A1*2A, CYP1A1*2B, GSTA1-52, GSTM1O, GSTM3B, GSTP1 I105V, GSTP1 A114V, GSTT1O, MPO-463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, and SULT1A1 R213H. RESULTS: GSTP1 105 strongly modified the relationship between 2,4-TDA in plasma and in urine: ValVal carriers had about twice as steep regression slope than IleIle carriers. A similar pattern was found for 2,6-TDA. CYP1A1*2A, GSTM1, GSTP1, GSTT1, and MPO possibly influenced the relationship between TDA in plasma and urine. CONCLUSION: Our results show, for the first time, genetic modification on the human TDI metabolism. The findings suggest that GSTP1 genotype should be considered when evaluating biomarkers of TDI exposure in urine and plasma. Moreover, the results support earlier findings of GSTP1 105 Val as protective against TDI-related asthma.
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| 4. |
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| 5. |
- Lindh, Christian, et al.
(författare)
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Biological monitoring of toluene diisocyanate (TDI) exposure by analysis of urine from exposed workers
- 2002
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Ingår i: Proceedings 50th ASMS Conference on Mass Spectrmetry and Allied Topics. ; , s. 655-656
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Konferensbidrag (refereegranskat)abstract
- A gas chromatography-negative ion chemical ionization-selected ion monitoring-mass spectrometry (GC-NICI-SIM-MS) method was used to quantitate the metabolite toluene diamine (TDA) in urine samples of toluene diisocyanate (TDI) exposed workers. In order to validate the biological monitoring method, air samples were collected and analyzed using a liquid chromatography tandem mass spectrometry (LC-MS) method. The urine samples were treated with liquid-liquid extraction to retrieve the toluene diamine (TDA). It was observed that urinary TDA levels were applicable fro biological monitoring of TDI exposure.
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| 6. |
- Littorin, Margareta, et al.
(författare)
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Eye and airway symptoms in low occupational exposure to toluene diisocyanate
- 2007
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Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 33:4, s. 280-285
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Exposure to diisocyanates is a well known occupational hazard. The objective of this study was to determine the possibility of an association between low exposure to toluene diisocyanate (TDI) (airborne isocyanates and biomarkers of isocyanates in plasma and urine) and symptoms of the eyes and upper and lower airways. Methods Altogether 136 workers occupationally exposed to TDI and 118 unexposed employees were studied. A physician compiled thorough medical and occupational histories and registered symptoms, total and work-related, of the eyes, nose, and lower airways. The exposure was assessed with personal air measurements and with biomarkers of exposure in plasma and urine. The average exposure in the ambient air at the workplace of the exposed participants was below 1 ppb. Results Compared with the unexposed group, the exposed workers reported more total symptoms of the eyes and lower airways, as well as Dose bleeding. A similar pattern, with even higher odds ratios, was observed for work-related symptoms. However, only eye symptoms proved to be significantly associated with the exposure, notably with all of the exposure measures. The risk was more pronounced for exposure to 2,4-TDI than for exposure to 2,6-TDI. Conclusions Even very low exposure to TDI is related to negative health effects on exposed workers. Clear dose-response relationships were observed between three different measures of exposure and symptoms of the eyes.
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| 7. |
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| 8. |
- Sennbro, Carl Johan
(författare)
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Biological and air monitoring of exposure to isocyanates
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Exposure to isocyanates may induce disorders in the airways of workers. Therefore, application, development and validation of methods for exposure assessment is of great importance. In the present study, we have determined the personal air and biomarker levels of isocyanates for a group of occupationally exposed workers (n=170) in different types of industrial processes. Also, the biomarker levels were determined for a control group consisting of occupationally unexposed workers (n=121). A method with filters impregnated with 1-(2-methoxyphenyl)piperazine (2MP) was used for personal air monitoring of exposure in different types of manufacturing processes. The field performance of the 2MP method was evaluated. Short-term stationary measurements was collected in parallel with an impinger method using dibutylamine (DBA) in toluene. Also, the long-term performance was evaluated by parallel sampling with consecutive sampling by the 2MP method itself. The 2MP method was found to underestimate the air levels of some isocyanates. Correction factors were calculated that may adjust for these observed losses. A new bioanalytical method for determination of biomarkers of aromatic diisocyanates was validated. This method is more convenient, better characterized and more robust than previous methods. The biomarker levels of aromatic diisocyanates were determined in the two groups of workers and upper reference limits (URLs) were calculated. The URLs may be useful in a screening test to assess whether a worker is occupationally exposed to diisocyanates or not. The biomarkers of 4,4'-methylene diisocyanate (MDI) were present in 97% of the occupationally unexposed workers. This indicates an unknown source of background exposure. For the exposed workers, there were strong correlations between urinary and plasma biomarker levels of isocyanates and between air and biomarker levels of isocyanates. The biomarkers of toluene diisocyanate (TDI), 1,5-naphthalene diisocyanate (NDI) and MDI were shown to be applicable as an index of exposure. For TDI, strategies for biological monitoring of exposure were established, and biological limit values were proposed.
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| 9. |
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| 10. |
- Sennbro, Carl Johan, et al.
(författare)
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Biological monitoring of exposure to toluene diisocyanate.
- 2004
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Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 30:5, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES :Toluene diisocyanate (TDI) is used in the manufacture of polyurethane and is a potent inducer of diseases of the airways. In this study, 2,4- and 2,6-toluenediamine in hydrolyzed urine and plasma were evaluated as biomarkers of exposure to 2,4- and 2,6-TDI, respectively. METHODS: For 81 exposed workers from nine different plants, the personal 8-hour time-weighted-average exposure to TDI was monitored by a filter method with 1-(2-methoxyphenyl)piperazine. In parallel, urinary samples (U1) were collected during the last 4 hours of the workshift. On a different occasion, blood samples and additional urinary samples (U2) were collected from the exposed workers, and also from a reference group consisting of 121 unexposed workers. The biomarker levels were determined in urine and plasma by the use of alkaline hydrolysis. RESULTS: There were strong associations between the personal air and biomarker levels, with correlation coefficients in the range of 0.75-0.88 for the U1 samples and in the range of 0.50-0.78 for the plasma samples. By weighted linear regression, the relations were calculated between the air and biomarker levels. The slopes of the obtained regression curves ranged from 1.8 to 2.7 m3/1 for air-urine and from 2.2 to 2.9 m3/1 for air-plasma, and the intercepts were all close to the origin of the coordinates. Through the extrapolation of these regression curves, biological exposure limits were calculated. CONCLUSIONS: The biological monitoring methods and strategies presented in this report are useful for assessing exposure to TDI in practice.
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