Oxidative stress and detoxification in reproduction with emphasis on glutathione and preeclampsia

Contains fulltext : 19213_oxidstand.pdf (publisher's version ) (Open Access)Oxidative stress is associated with several diseases including reproductive disorders and preeclampsia. Defence against oxidative stress is provided by numerous exogenous antioxidants (e.g. vitamins E and C) or endogenous enzyme systems (e.g. catalase and glutathione-related enzymes). When during pregnancy the maternal antioxidant capacity is insufficient to deal with the increased load of oxidative compounds, preeclampsia or the hemolysis, elevated liver enzymes and low platelets syndrome may occur. In this thesis several studies on glutathione and glutathione-related enzymes on male fertility, embryonic, foetal and placental development are presented). In addition, studies on the redox-balance of glutathione and other thiols in preeclampsia, and genetic polymorphisms in association with to oxidative stress in preeclampsia are described. From this thesis it may conclude that glutathione and related enzymes are correlated with male fertility, are important for normotensive pregnancy, whereas disturbances are seen in preeclampsia and the HELLP syndrome. Disturbances of thiol levels are associated with preeclampsia. Using the free-to-oxidised ratio of thiols we were able to demonstrate the presence of a transient oxidative stress during pregnancy, being even more pronounced in preeclampsia, disappearing after delivery. However, in women with severe preeclampsia a lower free-to-oxidised ratio for homocysteine is found after consecutive pregnancies, following their index-pregnancy. Therefore, the free-to-oxidised ratio for homocysteine may be a predictor for preeclampsia or may serve as indicator for the development of cardiovascular problems in later life. Oxidative stress during preeclampsia seems not to be associated with polymorphisms in the genes encoding for the p22phox subunit NAD(P)H oxidase or haptoglobin. However, as an angiogenic factor, haptoglobin may play a role during placental development223 p

The C242T-polymorphism of the NADPH/NADH oxidase gene p22phox subunit is not associated with preeclampsia

Item does not contain fulltextPre-eclampsia is a pregnancy-related multisystem disorder characterised by elevation of blood pressure and proteinuria, in which oxidative stress may play an important role. Blood pressure is partly controlled by O(-)(2) production by NADPH/NADH oxidase and recently it was shown that a C242T substitution in the p22phox gene was associated with coronary artery disease, in which elevated blood pressure and oxidative stress are also important pathophysiologic features. Therefore we studied the prevalence of the C242T polymorphism in the NADPH/NADH oxidase gene in women with pre-eclampsia and/or haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome as compared with women with a normotensive pregnancy. DNA from control women (n = 78), women with pre-eclampsia (n = 40), HELLP syndrome (n = 9) or women with HELLP complicated by pregnancy-induced hypertension or pre-eclampsia (n = 46) were tested for the presence of the C242T polymorphism by polymerase chain reaction followed by restriction fragment-length polymorphism. The prevalence of the homozygous CC-genotype was similar in the patient groups compared with controls. The allele frequency of the T-allele was 31% in both control and patient groups. In conclusion the C242T polymorphism in the p22phox subunit of the NADPH/NADH oxidase gene is not associated with pre-eclampsia. Therefore, oxidative stress generated by NADPH/NADH oxidase probably does not play a role in the development of pre-eclampsia

Distribution of components of the glutathione detoxification system across the human placenta after uncomplicated vaginal deliveries

The function of the glutathione-related detoxification system plays an important role to ensure an uncomplicated pregnancy outcome. This study was performed to investigate whether the components of the glutathione-related detoxification system are equally distributed among the different cotelydons in the human placenta. We measured glutathione, cysteine, glutathione S-transferase (GST) isoenzyme levels (GSTA1+A2, GSTP1, GSTM1 and GSTT1), enzyme activities of glutathione S-transferase and glutathione peroxidases, protein carbonyl levels, and antioxidant capacities at twelve different standardized positions in six placentae from healthy women after uncomplicated pregnancy and vaginal delivery. Data were statistically evaluated with a Friedman two-way ANOVA with Bonferroni correction. 'Foetal'-side values were not significantly different from those at the 'maternal'-side. Except for GSTA1+A2, no significant differences were found between different sampling sites indicating that the distribution of all parameters measured was homogenous throughout the placenta. Since levels of GSTA1+A2 were minor compared to those of GSTP1 and GSTT1, the clinical relevance of this heterogeneity may be limited. These results implicate that the location of sampling is not important as long as biopsies are taken from physiological cotelydons. (C) 2002 Elsevier Science Ltd. All rights reserved

Experiences of healthcare professionals with support for mesothelioma patients and their relatives: Identified gaps and improvements for care

Objective: To assess perspectives and experiences of healthcare professionals and other relevant stakeholders regarding psychosocial support and palliative care in mesothelioma patients and their relatives, to identify gaps and to explore potential improvements in current healthcare. Methods: Individual, semi-structured interviews were conducted with healthcare professionals and other relevant stakeholders. Interviews were transcribed verbatim and analysed thematically using ATLAS.ti. Results: In total, 16 respondents participated in an interview (69% women; mean age: 51.8 years (SD 12.41; range 28–75)). Four key themes were identified: (1) availability of tailored psychosocial and palliative care, (2) timely integration and organisation of psychosocial support and palliative care, (3) differences in provided support and care between healthcare professionals and hospitals and (4) training of healthcare professionals and stakeholders on psychosocial problems. Conclusion: Our study showed that psychosocial support and palliative care for patients with mesothelioma could be improved. A more fluent transition between primary and secondary cancer care and early integration of psychosocial support and palliative care is advised. Lastly, more attention is needed for psychosocial and palliative care in the basic medical training of healthcare professionals