Despite the wide use of silver nanoparticles (nano Ag), its toxicity still remains poorly understood. In this report, nano Ag induced an increase in platelet aggregation and procoagulant activation which are the key contributors to thrombotic diseases. In freshly isolated human platelets, nano Ag induced platelet aggregation and procoagulant activation evident by increased phosphatidylserine exposure and thrombin generation. Interestingly, the sub-threshold level of thrombin enhanced nano Ag-induced platelet activation significantly indicating that the prothrombotic effects of nano Ag might be further potentiated in activated platelets. An increase in intracellular calcium mediated nano Ag induced platelet activation and P-selectin expression, and serotonin release was also enhanced by nano Ag. Consistent with the in vitro results, exposure to nano Ag (0.05-0.1 mg/kg i.v. or 5-10 mg/kg intratracheal instillation) in vivo enhanced venous thrombus formation, platelet aggregation, and phosphatidylserine externalization ex vivo in rats suggesting that nano Ag, indeed, does enhance thrombus formation through platelet activation.

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Volume-based parameters of F-18 FDG PET-CT may have a role in providing prognostic information in NSCLC patients who have received surgical treatment.

BackgroundAssociations between cardiovascular diseases and mercury have been frequently described, but underlying mechanisms are poorly understood.ObjectivesWe investigate the procoagulant activation of erythrocytes, an important contributor to thrombosis, by low-level mercury to explore the roles of erythrocytes in mercury-related cardiovascular diseases.MethodsWe used freshly isolated human erythrocytes and ex vivo and in vivo thrombosis models in rats to investigate mercury-induced procoagulant activity.ResultsProlonged exposure to low-dose mercuric ion (Hg2+; 0.25–5 μM for 1–48 hr) induced erythrocyte shape changes from discocytes to echinocytes to spherocytes, accompanied by microvesicle (MV) generation. These MVs and remnant erythrocytes expressed phosphatidylserine (PS), an important mediator of procoagulant activation. Hg2+ inhibited flippase, an enzyme that recovers PS into the inner leaflet of the cell membrane, and activated scramblase, an enzyme that alters lipid asymmetry in the cell membrane. Consistent with these activity changes, Hg2+ increased intracellular calcium and depleted ATP and protein thiol. A thiol supplement reversed Hg2+-induced MV generation and PS exposure and inhibited the increase in calcium ion (Ca2+) and depletion of ATP, indicating that free-thiol depletion was critical to Hg2+-mediated procoagulant activity. The procoagulant activity of Hg2+-treated erythrocytes was demonstrated by increased thrombin generation and endothelial cell adhesion. We further confirmed Hg2+-mediated procoagulant activation of erythrocytes in ex vivo and in vivo rat thrombosis models, where Hg2+ treatment (0.5–2.5 mg/kg) increased PS exposure and thrombus formation significantly.ConclusionThis study demonstrated that mercury could provoke procoagulant activity in erythrocytes through protein-thiol depletion–mediated PS exposure and MV generation, ultimately leading to enhanced thrombosis.

Aims The dopamine transporter (DAT) actively translocates dopamine that is released from the presynaptic neurons across the membranes of nerve terminals into the extracellular space. We hypothesized that glucose loading‐induced changes in striatal DAT levels could be associated with food intake in humans. Materials and methods An intravenous bolus injection of 18F‐FP‐CIT was administered after infusion of glucose or placebo (normal saline), and emission data were acquired over 90 minutes in 33 healthy males. For a volume‐of‐interest‐based analysis, an atlas involving sub‐striatal regions of ventral striatum (VST), caudate nucleus and putamen was applied. DAT availability and binding potential (BPND) were measured using a simplified reference tissue method with cerebellum as the reference. Results The glucose‐loaded BPND from the VST negatively correlated with body mass index (BMI), whereas the placebo‐loaded BPND from the VST did not. After loading with glucose, there were substantial increases in BPNDs: 18.3%, 71.7% and 34.0% on average in the VST, caudate nucleus and putamen, respectively. Conclusion Striatal DAT changes after glucose loading, and BMI is associated with glucose‐loaded DAT availability, not with placebo‐loaded DAT availability. DAT might have a role in the reward system of eating behavior.

Bleeding is the most common and serious adverse effect of currently available antiplatelet drugs. Many efforts are being made to develop novel antithrombotic agents without bleeding risks. Shear stress-induced platelet aggregation (SIPA), which occurs under abnormally high shear stress, plays a crucial role in the development of arterial thrombotic diseases. Here, we demonstrate that protocatechuic acid (PCA), a bioactive phytochemical from Lonicera (honeysuckle) flowers, selectively and potently inhibits high shear (Ͼ10,000 s Ϫ1 )-induced platelet aggregation. In isolated human platelets, PCA decreased SIPA and attenuated accompanying platelet activation, including intracellular calcium mobilization, granule secretion, and adhesion receptor expression. The anti-SIPA effect of PCA was mediated through blockade of von Willebrand factor binding to activated glycoprotein Ib, a primary and initial event for the accomplishment of SIPA. Conspicuously, PCA did not inhibit platelet aggregation induced by other endogenous agonists like collagen, thrombin, or ADP that are important in both pathological thrombosis and normal hemostasis. Antithrombotic effects of PCA were confirmed in vivo in a rat arterial thrombosis model, where PCA significantly delayed the arterial occlusion induced by FeCl 3 . Of particular note, PCA did not increase bleeding times in a rat tail transection model, whereas conventional antiplatelet drugs, aspirin, and clopidogrel substantially prolonged it. Collectively, these results suggest that PCA may be a novel antiplatelet agent that can prevent thrombosis without increasing bleeding risks.

Background: The purpose of this study was to compare the incidence of thyroid cancer among patients with primary non-thyroid cancer, who showed focal thyroid uptake in ¹⁸F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT). Material and Methods: We reviewed a total of 22,674 FDG PET/CTs performed at our institution between March 2005 and June 2011. A retrospective review was conducted on 433 non-thyroid cancer patients (male: n = 90, female: n = 343) who had thyroid incidentaloma on FDG PET/CT. In 286 patients, diagnostic confirmation was done by ultrasound-guided fine needle aspiration biopsy (FNAB). Results: Among 22,674 FDG PET/CT scans, 483 subjects (2.1%) showed focal thyroid uptake. Among the 286 patients who underwent FNAB, 280 were included in the study. Of those, 68 patients (24.3%) demonstrated papillary thyroid carcinoma on the final pathologic findings. We divided patients into 7 groups depending on the primary cancer. Conclusion: In patients with cancer of non-thyroid origin, incidental FDG uptake in the thyroid gland was observed in 2.1% and associated with a 24.3% risk for well-differentiated thyroid carcinoma. However, there was no statistically significant difference in the malignant risk of focal FDG uptake of the thyroid gland according to the underlying primary non-thyroid cancer type.

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