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3. Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications.

Author

Dobrian, A, Morris, M, Taylor-Fishwick, D, Holman, Theodore, Imai, Y, Mirmira, R, and Nadler, J

Subjects
Inflammation, Lipoxygenase, Lipoxygenase inhibitors, Type 1 diabetes, Type 2 diabetes-related complications, Animals, Arachidonate 12-Lipoxygenase, Arachidonate 15-Lipoxygenase, Diabetes Complications, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Insulin-Secreting Cells, Lipoxygenase Inhibitors, Signal Transduction
Abstract

12-lipoxygenase (12-LOX) is one of several enzyme isoforms responsible for the metabolism of arachidonic acid and other poly-unsaturated fatty acids to both pro- and anti-inflammatory lipid mediators. Mounting evidence has shown that 12-LOX plays a critical role in the modulation of inflammation at multiple checkpoints during diabetes development. Due to this, interventions to limit pro-inflammatory 12-LOX metabolites either by isoform-specific 12-LOX inhibition, or by providing specific fatty acid substrates via dietary intervention, has the potential to significantly and positively impact health outcomes of patients living with both type 1 and type 2 diabetes. To date, the development of truly specific and efficacious inhibitors has been hampered by homology of LOX family members; however, improvements in high throughput screening have improved the inhibitor landscape. Here, we describe the function and role of human 12-LOX, and mouse 12-LOX and 12/15-LOX, in the development of diabetes and diabetes-related complications, and describe promise in the development of strategies to limit pro-inflammatory metabolites, primarily via new small molecule 12-LOX inhibitors.

Published
2019

4. Trends in occupational respiratory conditions with short latency in the UK.

Author

Barradas, A, Iskandar, I, Carder, M, Gittins, M, Fishwick, D, Seed, M, and Tongeren, M van

Subjects
HYPERSENSITIVITY pneumonitis, RESPIRATORY diseases, OCCUPATIONAL asthma, COMMUNICABLE diseases, METAL cutting
Abstract

Background Occupational short-latency respiratory disease (SLRD; predominantly asthma, rhinitis, hypersensitivity pneumonitis, and occupational infections) prevalence is difficult to determine but certain occupations may be associated with increased susceptibility. Aims This study aimed to examine which occupations and industries are currently at high risk for SLRD and determine their respective suspected causal agents. Methods SLRD cases reported to the SWORD scheme between 1999 and 2019 were analysed to determine directly standardized rate ratios (SRR) by occupation against the average rate for all other occupations combined. Results 'Bakers and flour confectioners' and 'vehicle spray painters' showed significantly raised SRR for SLRD in general, mostly due to occupational rhinitis (234.4; 95% CI 200.5–274.0) and asthma (63.5; 95% CI 51.5–78.3), respectively. Laboratory technicians also showed significantly raised SRR for occupational rhinitis (18.7; 95% CI 15.1–23.1), primarily caused by laboratory animals and insects. Metal machining setters and setter-operators showed increased SRR for occupational hypersensitivity pneumonitis (42.0; 95% CI 29.3–60.3), largely due to cutting/soluble oils. The occupation mostly affected by infectious disease was welding trades (12.9; 95% CI 5.7–29.3), mainly attributable to microbial pathogenicity. Conclusions This study identified the occupational groups at increased risk of developing an SLRD based on data recorded over a recent two-decade period in the UK. Occupational asthma and rhinitis were identified as the prevailing conditions and hypersensitivity pneumonitis as a potentially rising respiratory problem in the metalworking industry. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Determinants of health-related quality of life among residents with and without COPD in a historically industrialised area

Author

Blanc, Paul, Fishwick, D, Lewis, L, Darby, A, Young, C, Wiggans, R, Waterhouse, J, Wight, J, and Blanc, PD

Abstract

© 2014 The Author(s) Purpose: Chronic obstructive pulmonary disease (COPD) is associated with substantial morbidity, including impaired health-related quality of life (HRQoL). Despite the prominent role of occupational factors in the aetiology of COPD, the

Published
2014

33. Standards of care for occupational asthma

Author

Fishwick, D, Barber, C M, Bradshaw, L M, Harris-Roberts, J, Francis, M, Naylor, S, Ayres, J, Burge, P S, Corne, J M, Cullinan, P, Frank, T L, Hendrick, D, Hoyle, J, Jaakkola, M, Newman-Taylor, A, Nicholson, P, Niven, R, Pickering, A, Rawbone, R, Stenton, C, Warburton, C J, and Curran, A D

Published
2008
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34. The occupations at increased risk of chronic obstructive pulmonary disease (COPD): analysis of lifetime job-histories in the population-based UK Biobank Cohort

Author

De Matteis, S, Jarvis, D, Darnton, A, Hutchings, S, Sadhra, S, Fishwick, D, Rushton, L, Cullinan, P, and Health & Safety Executive

Subjects
Adult, Male, Respiratory System, OBSTRUCTIVE PULMONARY-DISEASE, State Medicine, Pulmonary Disease, Chronic Obstructive, Risk Factors, Forced Expiratory Volume, Occupational Exposure, Prevalence, Humans, Poisson Distribution, Prospective Studies, Occupations, 11 Medical and Health Sciences, Aged, Biological Specimen Banks, Science & Technology, Middle Aged, United Kingdom, respiratory tract diseases, Occupational Diseases, Spirometry, Female, HEALTH, Life Sciences & Biomedicine
Abstract

Occupational exposures are important, preventable causes of chronic obstructive pulmonary disease (COPD). Identification of COPD high-risk jobs is key to focus preventive strategies, but a definitive job-list is unavailable.We addressed this issue by evaluating the association of lifetime job-histories and lung function data in the population-based UK Biobank cohort, whose unprecedented sample size allowed analyses restricted to never-smokers to rule out the most important confounder, tobacco smoking. COPD was spirometrically-defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)

Published
2019

41. Letter to the editor

Author

Barber, C. M, Gordon, S. B, Curran, A. D, and Fishwick, D

Published
2001

47. Chronic bronchitis in textile workers

Author

Niven, R. McL., Fletcher, A. M., Pickering, C. A. C., Fishwick, D., Warburton, C. J., Simpson, J. C. G., Francis, H., and Oldham, L. A.

Published
1997

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