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| 2. |
- Mannes, Marco, et al.
(författare)
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Complement and platelets : prothrombotic cell activation requires membrane attack complex-induced release of danger signals
- 2023
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:20, s. 6367-6380
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Tidskriftsartikel (refereegranskat)abstract
- Complement activation in the diseases paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) results in cytolysis and fatal thrombotic events, which are largely refractory to anticoagulation and/or antiplatelet therapy. Anticomplement therapy, however, efficiently prevents thrombotic events in PNH and aHUS, but the underlying mechanisms remain unresolved. We show that complement-mediated hemolysis in whole blood induces platelet activation similarly to activation by adenosine 5 '-diphosphate (ADP). Blockage of C3 or C5 abolished platelet activation. We found that human platelets failed to respond functionally to the anaphylatoxins C3a and C5a. Instead, complement activation did lead to prothrombotic cell activation in the whole blood when membrane attack complex (MAC)-mediated cytolysis occurred. Consequently, we demonstrate that ADP receptor antagonists efficiently inhibited platelet activation, although full complement activation, which causes hemolysis, occurred. By using an established model of mismatched erythrocyte transfusions in rats, we crossvalidated these findings in vivo using the complement inhibitor OmCI and cobra venom factor. Consumptive complement activation in this animal model only led to a thrombotic phenotype when MAC-mediated cytolysis occurred. In conclusion, complement activation only induces substantial prothrombotic cell activation if terminal pathway activation culminates in MAC-mediated release of intracellular ADP. These results explain why anticomplement therapy efficiently prevents thromboembolisms without interfering negatively with hemostasis.
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| 3. |
- Messerer, Maria, et al.
(författare)
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Dietary supplement use and mortality in a cohort of Swedish men
- 2008
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Ingår i: British Journal of Nutrition. - : CAMBRIDGE UNIV PRESS. - 0007-1145 .- 1475-2662. ; 99:3, s. 626-631
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Tidskriftsartikel (refereegranskat)abstract
- The use of dietary supplements has increased substantially in most industrialized countries. The aim of this study was to prospectively examine the association between use of dietary supplements and all-cause mortality, cancer mortality and CVD mortality in men. We used the population-based prospective cohort of 38 994 men from central Sweden, 45-79 years of age, with no cancer or CVD at baseline and who completed a self-administered FFQ including questions on dietary supplement use and life-style factors in 1997. During average 7.7 years of follow-up, 3403 deaths were ascertained; among them, 771 due to cancer and 930 due to CVD (during 5.9 years of follow-up). In multivariate adjusted models including all men there was no association observed between use of any dietary supplement or of multivitamins, vitamin C, vitamin E or fish oil specifically and all-cause mortality, cancer or CVD mortality. Among current smokers, regular use of any supplement was associated with statistically significant increased risk of cancer mortality: relative risk (RR) 1.46 (95 % CI 1.06, 1.99). Among men reporting an inadequate diet at baseline (assessed by Recommended Food Score), there was a statistically significant inverse association between use of any dietary supplement and CVD mortality (RR 0.72; 95 % CI 0.57, 0.91), no associations were observed among men with adequate diets. In conclusion, we cannot exclude that the use of dietary supplements is harmful for smokers. On the other hand, among men with an insufficient diet, the use of supplements might be beneficial in reducing CVD mortality.
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| 4. |
- Messerer, Maria
(författare)
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Dietary supplements : trends, demographics and mortality among users
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dietary supplements have received growing attention in society and sales numbers indicate increased use. Still, time trends in prevalence of users have been unknown. In order to accurately explore associations between diet and diseases, valid assessment methods for micronutrient intake from foods and dietary supplements are needed. The prevalence of dietary supplement users in Sweden, estimated in three nationally representative surveys, conducted during the last decades, increased by 70% and was 22% and 33% for men and women, respectively, in 1997. Use of natural remedies increased threefold. The increase was observed in all age groups, all socio-economic groups, and all parts of Sweden. The use of these preparations was associated with several sociodemographic and health behaviour factors. The best predictors of use were age, sex and subjective health. Women and older individuals were more likely to be users as well as people reporting a poor health status. Subjects who were underweight and subjects reporting moderate to high levels of exercise were also more often users. To evaluate if a self-reported food frequency questionnaire (FFQ) can measure use of dietary supplements and the total micronutrient intake, sensitivity, specificity and validity was compared to fourteen 24-hour recalls (collected monthly by telephone) in 248 men (40-75 years old) in a random sample from central Sweden. The sensitivity of the FFQ for measuring use of dietary supplements was 78% and the specificity 93%. Validity for micronutrient intake (Spearman correlation coefficients) increased by 13% (from 0.49 to 0.62), when nutrients from supplements were included. The classification of micronutrient intake from the FFQ into corresponding quintile in the 24-hour recalls was also improved from 37% to 5 1 % when supplements were included. The average reproducibility (intraclass correlation coefficients) for total nutrient intake was 0.61 between two FFQs completed one year apart. The observed increase in the validity of micronutrient estimates due to inclusion of supplements has important implications for epidemiological studies. In a population-based prospective cohort of 48,645 Swedish men, we investigated the association between use of dietary supplement and all-cause, cardiovascular and cancer mortality. By linking the cohort to the Death Register and the Register of Causes of Death, 2499 deaths (all cause) was ascertained during 246,522 person-years of follow-up, while 540 deaths occurred due to cardiovascular diseases and 398 deaths due to cancer during 153,796 person-years of follow-up for the specific cause mortality. In the multivariate adjusted model, there was no association observed between use of dietary supplements and all-cause mortality, cardiovascular or cancer mortality. However, both confounding and reversed causality seemed to be important issues to consider in this type of study. Independent of adjusting for several lifestyle factors, there was still an adverse association among former smokers, between regular use of dietary supplements and all-cause mortality and a suggested association among current smokers. In conclusion, the use of dietary supplements is associated with several lifestyle factors and the prevalence of users has increased during the last decades. Thus, use of dietary supplements has to be considered in nutritional surveys and when assessing associations between diet and diseases. The adverse association found between use of dietary supplements and mortality among former/current smokers needs further evaluation.
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| 5. |
- Messerer, Maria, et al.
(författare)
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The validity of questionnaire-based micronutrient intake estimates is increased by including dietary supplement use in Swedish men
- 2004
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 134:7, s. 1800-5
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Tidskriftsartikel (refereegranskat)abstract
- Although many validation studies of FFQ have been reported, only a few addressed the effect of inclusion of dietary supplement use on the validity of micronutrient estimates. The purpose of the present study was to assess reproducibility and validity of a self-administered FFQ, intended to measure total nutrient intake from diet and from dietary supplements, in a random population-based sample of 248 middle-aged and elderly men (40-74 y old) in central Sweden. Fourteen 24-h recall interviews were used as the reference method. Participants were telephoned about once a month for 1 y, covering every day of the week, twice in random order. Spearman correlation coefficients increased 13% (from 0.49 to 0.62), between FFQ-based micronutrient estimates and the fourteen 24-h recall interviews (reference method) when supplement use was included. Correct classification into highest quintiles was also improved by 14% (from 37 to 51%). There were no differences in mean intraclass correlation coefficients for 1-y reproducibility between total micronutrient intake and micronutrients from foods only. The increase in the validity of micronutrient estimates due to inclusion of supplements in nutrient intake assessment has important implications for sample size in epidemiologic studies. Because a dramatic increase in dietary supplement use has occurred in recent decades in many countries, the issue of including supplements in dietary assessment should be of highest priority in nutritional epidemiologic studies of chronic diseases.
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