Inflammation-coagulation response and thrombotic effects induced by silica nanoparticles in zebrafish embryos

<p>Nowadays, nanotechnology environmental health and safety (nanoEHS) is gaining attention. We previously found that silica nanoparticles (SiNPs) could induce vascular endothelial damage. However, the subsequent toxicologic response to SiNPs-induced endothelial damage was still largely unknown. In this study, we explored the inflammation–coagulation response and thrombotic effects of SiNPs in endothelial cells and zebrafish embryos. For <i>in vitro</i> study, swollen mitochondria and autophagosome were observed in ultrastructural analysis. The cytoskeleton organization was disrupted by SiNPs in vascular endothelial cells. The release of proinflammatory and procoagulant cytokines including IL-6, IL-8, MCP-1, PECAM-1, TF and vWF, were markedly elevated in a dose-dependent manner. For <i>in vivo</i> study, based on the NOAEL for dosimetry selection, and using two transgenic zebrafish, Tg(mpo:GFP) and Tg(fli-1:EGFP), SiNPs-induced neutrophil-mediated inflammation and impaired vascular endothelial cells. With the dosage higher than NOAEL, SiNPs significantly decreased blood flow and velocity, exhibiting a blood hypercoagulable state in zebrafish embryos. The thrombotic effect was assessed by <i>o</i>-dianisidine staining, showed that an increasing of erythrocyte aggregation occurred in SiNPs-treated zebrafish. Microarray analysis was used to screen the possible genes for inflammation–coagulation response to SiNPs in zebrafish, and the JAK1/TF signaling pathway was further verified by qRT-PCR and Western blot assays. For in-deepth study, <i>il6st</i> was knocked down with specific morpholinos. The whole-mount <i>in situ</i> hybridization and qRT-PCR analysis showed that the expression <i>jak1</i> and <i>f3b</i> were attenuated in <i>il6st</i> knockdown groups. In summary, our data demonstrated that SiNPs could induce inflammation–coagulation response and thrombotic effects via JAK1/TF signaling pathway.</p

Prophylaxis for preventing venous thromboembolism in knee arthroscopy and soft tissue reconstruction: consensus statements from an international panel of experts

Purpose There is a lack of consensus regarding need for Venous Thrombo Embolism (VTE) prophylaxis following arthroscopic knee surgery and open soft tissue knee reconstruction. Clear cut guidelines like ones for trauma surgery and arthroplasty do not exist and the published literature is limited to case reports with a few society guidelines. Given this lack of consensus, we conducted a modified Delphi questionnaire of international experts to provide recommendations on this topic. Methods The consensus statements were generated using an anonymised 3 round modified Delphi questionnaire, sent to an international panel of 38 knee surgeons, with an 80% agreement being set as the limit for consensus. The responses were analysed using descriptive statistics with measures like mode, median and box plots. Feedback was provided to all panelists based on responses from the previous rounds to help generate the consensus. Results Six consensus statements were generated after the three rounds of Delphi. Patient factors, prolonged surgery duration and family history of thrombogenic events emerged as the main points to be taken into consideration for prophylaxis. Conclusion It was established through this study, that there exists a select group of patients undergoing arthroscopic surgery that justify the usage of VTE prophylaxis. The expert responses to most of the questions in different scenarios favoured usage of VTE prophylaxis based on patient factors like advanced age, past history of VTE, smoking, oral contraceptive use etc