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- Clarke, Robert, et al.
(författare)
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Lowering blood homocysteine with folic acid based supplements : Meta-analysis of randomised trials
- 1998
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Ingår i: British Medical Journal. - : BMJ. - 0959-8146. ; 316:7135, s. 894-898
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Forskningsöversikt (refereegranskat)abstract
- Objective: To determine the size of reduction in homocysteine concentrations produced by dietary supplementation with folic acid and with vitamins B-12 or B-6. Design: Meta-analysis of randomised controlled trials that assessed the effects of folic acid based supplements on blood homocysteine concentration. Multivariate regression analysis was used to determine the effects on homocysteine concentrations of different doses of folic acid and of the addition of vitamin B-12 or B-6. Subjects: Individual data on 1114 people included in 12 trials. Findings: The proportional and absolute reductions in blood homocysteine produced by folic acid supplements were greater at higher pretreatment blood homocysteine concentrations (P < 0.001) and at lower pretreatment blood folate concentrations (P < 0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12 μmol/l and of folate of 12 nmol/l (approximate average concentrations for Western populations), dietary folic acid reduced blood homocysteine concentrations by 25% (95% confidence interval 23% to 28%; P < 0.001), with similar effects in the range of 0.5-5 mg folic acid daily. Vitamin B-12 (mean 0.5 mg daily) produced an additional 7% (3% to 10%) reduction in blood homocysteine. Vitamin B-6 (mean 16.5 mg daily) did not have a significant additional effect. Conclusions: Typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 μmol/l to 8-9 μmol/l). Large scale randomised trials of such regimens in high risk populations are now needed to determine whether lowering blood homocysteine concentrations reduces the risk of vascular disease.
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| 3. |
- Blom, M., et al.
(författare)
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Human eosinophils express, relative to other circulating leukocytes, large amounts of secretory 14-kD phospholipase A2
- 1998
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Ingår i: Blood. - 1528-0020. ; 91:8, s. 3037-3043
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Tidskriftsartikel (refereegranskat)abstract
- Human eosinophils perform several functions dependent on phospholipase A2 (PLA2) activity, most notably the synthesis of platelet-activating factor (PAF) and leukotriene C4 (LTC4). Several forms of PLA2 have been identified in mammalian cells. In the present study, the 14-kD, secretory form of PLA2 was detected in human eosinophils by immunocytochemical staining with the specific monoclonal antibody (MoAb) 4A1. In contrast, preparations of neutrophils, monocytes, lymphocytes, and basophils did not show detectable staining. With two MoAbs in a sandwich enzyme-linked immunosorbent assay (ELISA), large amounts of sPLA2 were detected in lysates of eosinophils, that were 20-fold to 100-fold higher than in the other circulating leukocytes (ie, neutrophils, basophils, monocytes, and lymphocytes). In addition, with a commercially available sPLA2 activity assay kit, we were able to show high activity of sPLA2 in human eosinophils relative to neutrophils. Investigations at the ultrastructural level showed that sPLA2 in eosinophils is mainly located in specific granules. Immunoelectron microscopy also visualized sPLA2 within phagosomes after addition of opsonized particles to the eosinophils. However, sPLA2 was not detected in the cell-free supernatants of activated eosinophils, in contrast to eosinophil-cationic protein (ECP), which colocalizes with sPLA2 in resting eosinophils. These findings warrant further studies into the role of sPLA2 in eosinophil function.
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