Coulomb nanoradiator-mediated, site-specific thrombolytic proton treatment with a traversing pristine Bragg peak.

Traversing proton beam-irradiated, mid/high-Z nanoparticles produce site-specific enhancement of X-ray photon-electron emission via the Coulomb nanoradiator (CNR) effect, resulting in a nano- to micro-scale therapeutic effect at the nanoparticle-uptake target site. Here, we demonstrate the uptake of iron oxide nanoparticles (IONs) and nanoradiator-mediated, site-specific thrombolysis without damaging the vascular endothelium in an arterial thrombosis mouse model. The enhancement of low-energy electron (LEE) emission and reactive oxygen species (ROS) production from traversing proton beam-irradiated IONs was examined. Flow recovery was only observed in CNR-treated mice, and greater than 50% removal of the thrombus was achieved. A 2.5-fold greater reduction in the thrombus-enabled flow recovery was observed in the CNR group compared with that observed in the untreated ION-only and proton-only control groups (p < 0.01). Enhancement of the X-ray photon-electron emission was evident from both the pronounced Shirley background in the electron yield and the 1.2- to 2.5-fold enhanced production of ROS by the proton-irradiated IONs, which suggests chemical degradation of the thrombus without potent emboli.

Stimulatory effect of an algal fucoidan on the release of vascular endothelial tissue-type plasminogen activator as a mechanism of fucoidan-mediated thrombolysis.

Identifying a pharmacological means for increasing the production of tissue-type plasminogen activator (t-PA) is always desirable to cure impaired production of this enzyme. An algal fucoidan has been shown to exhibit both novel thrombolytic and synergistic stimulatory effects in a mouse thrombosis model. The plasma levels of active t-PA were measured in mouse arterial thrombus models that were treated with various fucoidans to investigate the mechanism of thrombolysis. The mean plasma level of active t-PA after the infusion of fucoidan was 2.136 ±â€Š0.231 ng/ml for nonthrombolytic Fucus fucoidan and 3.917 ±â€Š0.0.529 ng/ml for thrombolytic Undaria fucoidan, which resulted in a 1.56-2.29-fold increase compared with the healthy control group (1.706 ±â€Š0.194 ng/ml) and the untreated thrombus group (2.506 ±â€Š0.301 ng/ml) (P < 0.01). An algal fucoidan has demonstrated to exert a thrombolytic and stimulatory effect via the induction of t-PA release in a dose-dependent manner in an arterial thrombosis model.

Algal fucoidan, unlike heparin, has thrombolytic activity in a murine arterial thrombosis model.

Thrombolytic effects of fucoidans were investigated in the FeCl3-induced arterial thrombus mouse model and compared with heparin and tissue plasminogen activator (t-PA). Thrombosis model was made by applying 5% FeCl3 on the carotid artery of a Balb/c mouse. Twenty minutes after complete occlusion, a couple of test agents including fucoidan were infused into each mouse group with various doses intravenously, before measuring the time to reperfusion. The occluded arteries were reperfused 37.5 ± 12.4 min after administration of unfractionated fucoidan from Undaria pinnatifida sporophylls (UPS-UF) with a dose of 100 mg/kg. In the mice given either a low-molecular-weight UPS fucoidan or fucoidan source from Fucus vesiculosus (FV-UF), reperfusion was delayed at 55.0 ± 8.0 min with a higher reperfusion effective dose (RED) of 1 g/kg or at 63.3 ± 7.2 at RED of 200 mg/kg, respectively. In the control mice given t-PA of 15 mg/kg, reperfusion occurred at 24.8 ± 6.5 min after administration. In contrast, reperfusion was not observed in the occluded mice given heparin (P < 0.001) in the range of 60-1000 mg/kg. Minimal injection of fucoidan in addition to a given t-PA-enabled restoration of blood flow in the blocked artery without reocclusion at 17.2 ± 2.3 min postinjection (P < 0.002). In conclusion, algal fucoidan has both thrombolytic activity and a stimulatory effect on the thrombolytic activity of t-PA in a dose-dependent manner at an arterial thrombosis model.

An antithrombotic fucoidan, unlike heparin, does not prolong bleeding time in a murine arterial thrombosis model: a comparative study of Undaria pinnatifida sporophylls and Fucus vesiculosus.

The antithrombotic activities and bleeding effects of selected fucoidans (source from either Undaria pinnatifida sporophylls or from Fucus vesiculosus) have been compared with heparin in the ferric chloride-induced arterial thrombus mouse model. Thrombosis was induced by applying 5% ferric chloride for 3 min on the carotid artery region of Balb/c mouse. Five minutes prior to thrombus induction, mice were infused through the tail vein with either saline (control) or polysaccharides. Either fucoidan or heparin was dosed at 0.1, 1.25, 2.5, 5.0, 10, 25, or 50 mg/kg intravenously (i.v.) The carotid blood flow was monitored until more than 60 min post-thrombus induction. Mouse tail transection bleeding time was measured up to 60 min after making a cut in the mouse tail. Both antithrombotic and bleeding effects were observed in a dose-dependent manner for both fucoidans and heparin. Thrombus formation was totally (reflected by Doppler flow meter) inhibited at either 5 or 50 mg/kg of unfractionated Undaria fucoidan or a low-molecular-weight Undaria fucoidan fraction, respectively, without prolonging the time-to-stop bleeding compared with the control (p < 0.01). The total inhibition of thrombus formation was observed for unfractionated Fucus fucoidan at 25 mg/kg where the time-to-stop bleeding was still significantly prolonged, by as much as 8 ± 1.7 min (p < 0.02). In contrast the heparin-treated group showed total inhibition of thrombus formation even at a small dose of 0.8 mg/kg (400 IU) at which bleeding continued until 60 min. In conclusion algal fucoidans are highly antithrombotic without potential haemorrhagic effects compared with heparin in the arterial thrombus model, but this property differs from algal species to species, and from the molecular structure of fucoidans.

Effects of seed layers on structural, morphological, and optical properties of ZnO nanorods.

We studied the effects of seed layers on the structural and optical properties of ZnO nanorods. ZnO and Ag-doped ZnO (ZnO:Ag) seed layers were deposited on glass substrates by magnetron co-sputtering. ZnO nanorods were grown on these seed layers by the chemical bath deposition in an aqueous solution of Zn(NO3)2 and hexamethyltetramine. SEM micrographs clearly reveal that ZnO nanorods were successfully grown on both kinds of seed layers. The XRD patterns indicate that crystallization of ZnO nanorods is along the c-axis. Meanwhile, the packing density and the vertical alignment of the ZnO nanorods on the ZnO seed layer are better than those of the ZnO nanorods on ZnO:Ag. The enhanced growth of nanorods is thought to be due to the fact that the ZnO layer exhibits a higher crystalline quality than the ZnO:Ag layer. According to the low-temperature photoluminescence spectra, the ZnO nanorods on the ZnO seed layer show a narrow strong ultraviolet emission band centered at 369 nm, while those on ZnO:Ag exhibit multiple bands. These results are thought to be related with the crystallinity of ZnO nanorods, the morphologies of ZnO nanorods, and the reflectivities of seed layers. More detailed studies for clarification of the seed layer effect on the growth of ZnO nanorods are desirable.