Regulation of tissue factor-induced coagulation and platelet aggregation in flowing whole blood.

Photochemically induced thrombosis (a thrombin-dependent process) was measured in rats treated with moderate doses of anticoagulants, but which appeared to be unchanged. We considered the possibility that platelet-inhibiting agents, which also indirectly inhibit coagulation, would act as more potent antithrombotic agents. Inhibitors used as such were prostaglandin E1 (PGE1), which elevates cyclic AMP levels, and the P2Y12 ADP-receptor antagonist, AR-C69931MX. Effects of these agents were investigated in an ex vivo model system, in which whole blood under coagulant conditions was perfused over fibrinogen at defined wall shear rate. Perfusion of blood (rat or human) in the presence of tissue factor resulted in deposition of activated platelets and subsequent aggregate formation, along with exposure of procoagulant phosphatidylserine (PS) on the platelet surface and formation of fibrin fibers. In the presence of PGE1 aggregation was completely inhibited, but platelet adhesion and PS exposure were only party reduced, while fibrin formation was hardly affected. Treatment with AR-C69931MX caused similar, but less complete effects. These results indicate that in tissue factor-triggered blood under conditions of flow: (i) the platelet procoagulant response is independent of aggregate formation; (ii) the platelet-inhibiting effect of PGE1 and AR-C69931MX is sufficient to suppress aggregation, but not platelet adhesion and coagulation. These platelet inhibitors thus maintain their aggregation-inhibiting effect at sites of thrombin formation.

In vitro iron availability from iron-fortified whole-grain wheat flour.

Iron deficiency is the most common nutritional disorder worldwide. Iron fortification of foods is considered to be the most cost-effective long-term approach to reduce iron deficiency. However, for fortified foods to be effective in reducing iron deficiency, the added iron must be sufficiently bioavailable. In this study, fortification of whole-grain wheat flour with different sources of iron was evaluated in vitro by measuring the amount of dialyzable iron after simulated gastrointestinal digestion of flour baked into chapatis and subsequent intestinal absorption of the released iron using Caco-2 cell layers. The dialyzability of iron from iron-fortified wheat flour was extremely low. Additions of 50 mg/kg iron to the flour in the form of ferrous sulfate, Ferrochel amino acid chelate, ferric amino acid chelate taste free (TF), Lipofer, ferrous lactate, ferrous fumarate, ferric pyrophosphate, carbonyl iron, or electrolytic iron did not significantly increase the amount of in vitro dialyzable iron after simulated gastrointestinal digestion. In contrast, fortification of flour with SunActive Fe or NaFeEDTA resulted in a significant increase in the amount of in vitro dialyzable iron. Relative to iron from ferrous sulfate, iron from SunActive Fe and NaFeEDTA appeared to be 2 and 7 times more available in the in vitro assay, respectively. Caco-2 cell iron absorption from digested chapatis fortified with NaFeEDTA, but not from those fortified with SunActive Fe, was significantly higher than from digested chapatis fortified with ferrous sulfate. On the basis of these results it appears that fortification with NaFeEDTA may result in whole-grain wheat flour that effectively improves the iron status.

Fish oil inhibits photochemically induced thrombosis in the guinea pig in a dose dependent manner.

The dose-response effect of dietary fish oil was investigated in the photochemically induced thrombosis model in guinea pigs. In this arterial thrombosis model thrombus formation was evaluated by determination of different occlusion parameters (percentage of occlusion, area under the blood flow curve, time to first occlusion, spontaneous reflow). Sixty guinea pigs (7 weeks old) were randomly assigned to and fed a 40 energy % diet containing increasing amounts (0, 5.5, 17 and 36 energy %) of fish oil for four weeks. Arterial thrombosis was induced in the femoral artery by free radical damage and subsequent thrombus formation. Increasing fish oil concentrations in the diet were associated with a linear decrease (p<0.001) in the percentage of occlusion (calculated as a decrease in blood flow) and a linear increase in area under the blood flow curve/begin flow (p<0.001). The time to thrombus formation was not significantly prolonged in any group. However the frequency of animals in which complete occlusion of the femoral artery was not obtained during the thrombosis induction and subsequent observation period was higher in the groups receiving the two highest doses of fish oil. Spontaneous reflow correlated positively (p<0.013) with increasing dietary fish oil content. In conclusion, our data indicates that dietary fish oil inhibits photochemically induced thrombosis in this animal model of arterial thrombosis in a dose dependent manner.