Comparison of the effects of two low fat diets with different alpha-linolenic:linoleic acid ratios on coagulation and fibrinolysis.

Fish oils rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been demonstrated to alter coagulation and fibrinolysis variables. This study compared the effects of a traditional cholesterol-lowering diet and a similar diet, which had 50% of the linoleic acid (LA) replaced with the 18 carbon n-3 fatty acid, alpha-linolenic acid (ALA), on selected hemostatic variables. After a 2-week run-in diet with 39.5% total energy (en) from fat, 29 healthy male subjects consumed a 31.5% en fat diet with approximately 7% en from polyunsaturated fat and an ALA:LA ratio of either 1:1.2 (ALA-rich, n=15) or 1:21 (LA-rich, n=14) for 6 weeks. Blood was collected at the beginning, middle and end of test diets for analysis of Factor VIIc and VIIIc, fibrinogen, von Willebrand factor, activated protein C resistance (APC resistance), tissue plasminogen activator and plasminogen activator inhibitor type-1 activities and/or protein concentrations and platelet fatty acids. The ALA-rich diet tripled the percentage of platelet EPA, (P < 0.0005) but had little effect on coagulation and fibrinolysis. The APC ratio demonstrated increased anticoagulant activity on the ALA-rich diet (P < 0.001) only. Studies in patients with vascular pathologies are indicated to corroborate the current findings. Greater ratios of ALA:LA, achievable only with greater amounts of polyunsaturated fat, may be necessary to produce the effects demonstrated after feeding fish oils.

Replacement of linoleic acid with alpha-linolenic acid does not alter blood lipids in normolipidaemic men.

The effect of partial dietary replacement of linoleic acid (18:2n-6; linoleic acid-rich diet) with alpha-linolenic acid (18:3n-3; alpha-linolenic acid-rich diet) on plasma lipids was investigated in twenty-nine healthy young men. After a 2-week stabilization period subjects were randomly assigned to either the alpha-linolenic acid-rich diet group (n 15), receiving a mean of 10.1 g of alpha-linolenic acid and 12.1 g of linoleic acid/d, or the linoleic acid-rich diet group (n 14), receiving a mean of 1.0 g of alpha-linolenic acid and 21.0 g of linoleic acid/d, for a 6-week test period. Blood samples were taken at the commencement of the stabilization period and at the start (week 0), midpoint (week 3) and endpoint (week 6) of the test period and plasma lipids analysed. The changes occurring on the linoleic acid-rich diet and alpha-linolenic acid-rich diet were compared but no significant differences in the changes in plasma total cholesterol, LDL-cholesterol, HDL-cholesterol, the subfractions HDL2 and HDL3 or triacylglycerols were found. These results indicate that dietary replacement of linoleic acid with alpha-linolenic acid in the diet of healthy male subjects offers similar cardioprotective benefits with respect to lipid metabolism.

Involvement of platelets in stimulating osteogenic activity.

Osteoblast-like cells have been shown to be sensitive to the proliferative action of a wide variety of growth factors. Many of these growth factors have been isolated from platelets and are thought to be released at local sites in response to injury. In this study, we tested whether human platelet concentrate, as a supplement to basic medium, would support the proliferative and functional activity of human fetal osteoblast-like cells in both short-term and long-term culture. In short-term studies, uptake of [3H]thymidine was increased in platelet-treated cultures by more than 4-fold compared with 10% serum-supplemented controls. When cultured for prolonged periods on coverslips, the cells formed multilayers, with a collagen-based matrix separating the layers. Long-term cultures that were treated with 1.5% (vol/vol) platelets in serum-supplemented medium showed increases in the depth of the multilayers of as much as 36-fold at 30 days after confluence, compared with the 10% serum-supplemented controls; this difference persisted until day 50. Incorporation of growth factor in the matrix was examined with the use of colloidal gold immunoelectron microscopy. Immunogold labeling intensities for transforming growth factor-beta 1 were significantly lower in the platelet-treated cultures at 20 days and then increased to a maximum level of 2.1-fold more than in the controls at 40 days. Labeling intensities for insulin-like growth factor-I and basic fibroblast growth factor were significantly lower in the platelet-treated cultures than in the controls at all stages of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of growth factor incorporation into ECM of human osteoblast-like cells in vitro by 17 beta-estradiol.

Human fetal osteoblast-like cells formed a regular multilayered structure in vitro with an extensive collagen-based extracellular matrix. With colloidal gold immunocytochemistry, labels for alkaline phosphatase and osteocalcin were distributed in a relatively diffuse pattern, in contrast to the bone growth factors, insulin-like growth factors I and II (IGF-I and IGF-II), transforming growth factor-beta 1 (TGF-beta 1), and basic fibroblast growth factor, which were colocalized in the collagenous matrix of the multilayer. The inclusion of 17 beta-estradiol (10(-11) to 10(-9) M) in the culture medium increased multilayer depths, increased labeling for IGF-I, IGF-II, and TGF-beta 1, and resulted in earlier detection of TGF-beta 1 label. In contrast, the increase in multilayer depth resulting from treatment with human platelets, an exogenous source of growth factors, was not accompanied by an increase in matrix IGF-I, IGF-II, or TGF-beta 1 label, suggesting a particular effect of estradiol to facilitate this process. Because growth factors in bone matrix may act as coupling agents when released during resorption, reduced growth factor incorporation in the presence of reduced sex steroid concentrations may lead to uncoupling of resorption and subsequent formation.