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Ferromagnetic resonance (FMR) and ac conductivity have been applied to study a polymer composite containing as filler a binary mixture of magnetite (Fe3O4) and cementite (Fe3C) nanoparticles (30-50 nm) dispersed in a diamagnetic carbon matrix, which was synthesized by the carburization of nanocrystalline iron. Ac conductivity measurements showed thermally activated behavior involving a range of activation energies and power law frequency dependence at high frequencies similar to conducting polymer composites randomly filled with metal particles. Ferromagnetic resonance measurements revealed a relatively narrow FMR line at high temperatures indicating the presence of ferromagnetic nanoparticles, where thermal fluctuations and interparticle interactions determine the FMR temperature variation. An abrupt change of the FMR spectra was observed at T

The sample of iron carbide has been prepared using carburisation of iron with ethylene/hydrogen mixture. After carburisation, the sample was characterized by using XRD and scanning electron microscopy. XRD revealed the presence of cementite phase only. The mean size of cementite crystallites was determined to be 46 nm. The FMR absorption signals have been investigated in the temperature range from liquid helium up to room temperature. The asymmetric, very broad and intense FMR line was registered and decomposed in two Lorentzian-shape components (low- and high-field). The main high-field component shifts toward low magnetic fields with decreasing temperature. At 75 K a phase transition was observed due to the freezing of the non-magnetic matrix. Additionally, the spin glass state was recorded below 30 K.

Three powder samples with different content of iron carbide in a carbon matrix have been synthesised by carburisation of nanocrystalline iron with methane. The samples have been characterised by XRD and TEM methods. The mean crystallite size of the obtained iron carbide has been found to be in the range from 41 to 67 nm. The magnetic resonance measurements of these samples have been performed at room temperature. Very intense magnetic resonance lines have been recorded for each of the samples. A resonance field, an integral intensity and a linewidth strongly depend on the concentration of iron carbide. The observed magnetic resonance lines have been fitted with two Lorentzian-shape lines, one centred at lower and the other at higher magnetic fields. Strong magnetic anisotropy was observed for all the samples and for the sample with lower concentration of iron carbide it is more intense. The resonance absorption signal arises from the agglomerates of iron carbide nanoparticles interacting strongly among themselves. The observed shift of the resonance field is connected with a strong ferromagnetic interaction between agglomerates of nanoparticles. © 2004 Elsevier Ltd. All rights reserved.

In our previous experiments we showed that the prototype member of the AT1 receptor antagonists (AT1-As) family, losartan, prevented the development of arterial and venous thrombosis in rats. Recent studies have demonstrated that apart from blocking AT1 receptor, losartan is also a competitive antagonist to thromboxane A2/prostaglandin H2 receptor (TP receptor). Thus, we decided to assess if this feature could contribute to the antithrombotic action of losartan.We compared the influence losartan, its active metabolite EXP3174 and valsartan on rat platelet adhesion to fibrillar collagen and platelet aggregation in response to thromboxane A2 analogue, U46619. We also assessed the efficacy of these drugs in platelet-dependent pulmonary thrombosis in mice as well as preventive and therapeutic models of venous thrombosis in rats.All the three compounds, given in a single dose, inhibited rat platelet adhesion to fibrillar collagen and platelet aggregation induced with U46619 in vitro and ex vivo, with the action of losartan being much more pronounced than that of EXP3174 or valsartan. Losartan also more effectively protected mice from death in response to the intravenous injection of collagen / epinephrine and it was the only compound which reduced mice mortality after the intravenous injection of U46619. In contrast, all the three AT1 receptor antagonists exerted a similar thrombolytic action and comparably decreased the thrombus weight in the therapeutic and preventive model of venous thrombosis, although in the latter case a high dose of losartan was slightly more effective than a corresponding dose of EXP3174 and valsartan.Since losartan is endowed with a relatively low affinity towards the AT1 receptor, we conclude that its superiority over EXP 3174 and valsartan in inhibiting thrombocyte function and platelet-dependent thrombosis could result from its stronger action on the TP receptor. This feature seems to be less important in the thrombolytic effect of AT1-As and in the inhibition of the venous thrombosis development, in which platelets play only a minor role.

Drugs blocking the renin - angiotensin system, angiotensin converting enzyme inhibitors and AT1 receptor antagonists, among many pharmacological effects may exert an antithrombotic action. The mechanisms, which mediate their antithrombotic activity are associated with enhanced nitric oxide and prostacyclin release or with attenuation of angiotensin II action (Fig. 1, 2). Nevertheless, endothelium plays an important role in this process linking the renin-angiotensin and fibrinolysis / coagulation systems.

The aim of the study was to evaluate the effect of losartan on rat platelet adhesion to fibrillar collagen. Washed platelets were counted before and after 15 minutes incubation with collagen (50 microg/ml) and the percentage of adhering platelets was calculated as the index of their adhesion. When the platelets were incubated with collagen 40.8 +/- 0.3% of the platelets adhered. Losartan produced a dose dependent decrease in a number of adhering platelets both when the drug was administered to the animals ex vivo at doses of 3, 10 and 30 mg/kg (p0.01-0.001) or was added to the preparation of washed platelets in vitro in concentrations of 10(-8)-10(-5) M (p0.01-0.001). In the next step of the study we assessed the influence of L-NAME (10 mg/kg ex vivo, 30 microM in vitro) and indomethacin (2.5 mg/kg ex vivo, 30 microM in vitro) on the antiadhesive effect of losartan (10 mg/kg ex vivo, 10(-6) M in vitro). Blockade of nitric oxide synthase with L-NAME partially reversed the antiadhesive effect of losartan both ex vivo and in vitro. Indomethacin diminished the inhibitory effect of losartan on platelet adhesion when administered ex vivo, but it failed to modify this parameter when added to the suspension of platelets in vitro. In conclusion, losartan reduces platelet adhesion to fibrillar collagen in a dose-dependent manner. The observed action of losartan seems to be mediated mainly by endothelium- and platelet-derived nitric oxide.

Angiotensin-(1-7) [Ang-(1-7)] is an active member of renin-angiotensin system (RAS). It counterbalances vasoconstriction, mitogenic, arrhythmogenic and prothrombotic actions of Ang II. Inducing natiuresis and diuresis opposes also the water and sodium retention produced by Ang II. Till now the specific receptor side for Ang-(1-7) has been not cloned, but the current data strongly suggest that an interaction (cross-talk) between angiotensin receptors may play a role in the effects of Ang-(1-7).

Recent data suggest that hypotensive effect of losartan may not be attributed solely to AT1-receptor blockade, but also to excessive AT2 or other receptors stimulation by elevated angiotensin II and its derivative peptides. Therefore in the present study we examined the effect of angiotensin II on mean blood pressure after AT -receptor blockade with losartan. Male Wistar rats were anaesthetised and received injection of either losartan (30 mg/kg, 1 ml/kg, i.v.) or saline (the same volume and route) followed by bolus injection of angiotensin II (100, 300 or 1,000 ng/kg; 1 ml/kg, i.v.) or 1-hour infusion of angiotensin II (200 ng/kg/min; 2.5 ml/kg/h, i.v.). Control animals received saline instead. Angiotensin II, given either as the injection or the infusion, caused an evident increase in mean blood pressure (p ranged from 0.05 to 0.001 depending on the experimental group). Losartan caused a rapid drop in mean blood pressure and blunted the hypertensive effect of angiotensin II (p0.01). Moreover, in the losartan-pretreated animals the hypotensive phase was enhanced by the infusion, but not single injection of angiotensin II, which was most evident from the 30 th minute of observation (p0.05 vs control). In conclusion, hypotensive effect of losartan may be amplified by simultaneous increase in angiotensin II level, the situation observed during chronic AT1-receptor blockade.