| 26. |
- Orellana Pozo, Cecilia
(author)
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The association between hormonal/reproductive factors and the risk of developing rheumatoid arthritis
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Rheumatoid arthritis (RA) is a chronic inflammatory disease which leads to joint damage and bone destruction, with a complex interplay of genetic and environmental factors involved in its etiology. RA is more common among women than men at all ages, but the gender difference seems to be highest before menopause. It has been hypothesized that changes in female hormonal levels might have a role in RA pathogenesis. The overall aim of this thesis was to study the association between hormonal/reproductive factors and the risk of RA and to determine whether these factors were differently associated with serological phenotypes of the disease (according to the presence/absence of anti-citrullinated peptides antibodies (ACPA) and rheumatoid factor (RF)). This thesis is based on information from two large studies. Three articles were based on the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA), a population-based case- control study comprising incident RA cases. The study population were people aged 18 and above, living in diverse geographical parts of Sweden from 1996. Controls were randomly selected from the population register and matched to the cases by age, sex and residential area. Cases and controls completed an extensive questionnaire, collecting information about life- style/environmental exposures. One article was based on the Nurses’ Health Study (NHS), which consists of two prospective cohorts of female nurses in the USA. Data collection started in 1976 (women aged 30-55 years) and 1989 (women aged 25-42 years). Both cohorts of the NHS were followed via biennial questionnaires about diseases, lifestyle and health practices. According to our results, parous women had an increased risk of ACPA-negative RA compared with nulliparous women, aged 18-44 years. The increased risk was attributable to an elevated risk during the postpartum period, and to a young age at first birth. Older age at first birth seemed to be associated with a decreased risk of ACPA-positive RA. Parous women who breastfed for more than a year had a decreased risk of ACPA-positive RA compared with parous women who breastfed for up to 6 months. This decreased risk was non-significant after adjustment for smoking. Ever oral contraceptive use was significantly associated with a decreased risk of ACPA- positive RA, while a longer duration of use was significantly associated with a decreased risk for both RA subsets. Postmenopausal women had an increased risk of seronegative RA, but they had no association with the onset of seropositive RA. Women with a long duration of postmenopausal hormone therapy (PMH) had an increased risk of seropositive RA in the NHS. Finally, in the EIRA study, postmenopausal women who were currently using PMH at onset of their disease had a decreased risk of ACPA-positive RA. This decreased risk was mainly observed among women aged 50-59 years, with a short duration of use (<7 years), and only among users of a combined therapy of estrogen and progestogens. Further research is required to explore the biological mechanisms behind our findings, but our results contribute to the knowledge of hormonal/reproductive factors, and their impact on the serological phenotypes of RA.
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| 27. |
- Pikwer, Mitra, et al.
(author)
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Parity influences the severity of ACPA-negative early rheumatoid arthritis : a cohort study based on the Swedish EIRA material
- 2015
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 17
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Journal article (peer-reviewed)abstract
- Background: In women with rheumatoid arthritis (RA) it has been observed that during pregnancy a majority of patients experience amelioration, but after delivery a relapse of the disease is common. However, there are few studies, with diverging results, addressing the effect of parity on the severity of RA over time. Our aim was to explore the impact of parity, with stratification for anti-citrullinated protein antibody (ACPA) status as well as for onset during reproductive age or not. Methods: Female RA cases aged 18-70 years were recruited for the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Information on disease severity (the health assessment questionnaire (HAQ) and the disease activity score 28 (DAS28)) was retrieved from the Swedish Rheumatology Quality Register at inclusion and 3, 6, 12 and 24 months after diagnosis. Mixed models were used to compare mean DAS28 and HAQ scores over time in parous and nulliparous women. Mean differences at individual follow-up visits were compared using analysis of covariance. The odds of having DAS28 or HAQ above the median in parous verus nulliparous women were estimated in logistic regression models. Results: A total of 1237 female cases (mean age 51 years, 65 % ACPA-positive) were included. ACPA-negative parous women, aged 18-44 years, had on average 1.17 units higher DAS28 (p < 0.001) and 0.43 units higher HAQ score (p < 0.001) compared to nulliparous women during the follow-up time, adjusted for age. In this subgroup, the average DAS28 and HAQ scores were significantly higher in parous women at all follow-up time points. Younger parous ACPA-negative women were significantly more likely to have DAS28 and HAQ values above the median compared to nulliparous women at all follow-up visits. No association between parity and severity of ACPA-positive disease was observed. Conclusions: Parity was a predictor of a more severe RA among ACPA-negative younger women, which might indicate that immunomodulatory changes during and after pregnancy affect RA severity, in particular for the ACPA-negative RA phenotype.
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| 28. |
- Törnvall, Ulrika, et al.
(author)
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Stability of immobilized Candida antarctica lipase B during chemo-enzymatic epoxidation of fatty acids
- 2007
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In: Enzyme and Microbial Technology. - : Elsevier BV. - 0141-0229. ; 40:3, s. 447-451
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Journal article (peer-reviewed)abstract
- The parameters affecting the lipase activity and operational lifetime during chemo-enzymatic epoxidation of fatty acids were investigated. Immobilized Candida antarctica lipase B (Novozym (R) 435) was incubated in the presence of various reaction components (i.e. toluene, water, H2O2, oleic acid, perpalmitic acid, and epoxystearic acid, respectively) at temperatures between 20 and 60 degrees C followed by measurement of residual enzyme activity. Epoxystearic acid was shown to slightly inactivate the enzyme at 50 degrees C, while oleic acid and perpalmitic acid did not. No deactivation of the enzyme was observed in presence of toluene/water mixture within 48 h at 20-60 degrees C. In the presence of 6-12 M hydrogen peroxide, the enzyme was rather stable at 20 degrees C, while at 60 degrees C the enzyme lost activity rapidly, with the rate of deactivation increasing with increasing hydrogen peroxide concentration. These results imply that temperature control and careful dosage of hydrogen peroxide would be essential in an industrial chemo-enzymatic process. (c) 2006 Elsevier Inc. All rights reserved.
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