Sevoflurane anaesthesia induces late apoptosis in the colonic and laryngeal cancer cells investigated. Although the results obtained may indicate that an anaesthetic gas mixture containing sevoflurane induces p53-dependent apoptosis in the Caco-2 cells, the mechanism of apoptosis induction is unclear and remains to be elucidated.

Silver nanoparticles (AgNPs) are one of the most investigated metal-based nanomaterials. Their biocidal activity boosted their application in both diagnostic and therapeutic medical systems. It is therefore crucial to provide sound evidences for human-related safety of AgNPs. This study aimed to enhance scientific knowledge with regard to biomedical safety of AgNPs by investigating how their different surface properties affect human immune system. Methods: preparation, characterization and stability evaluation was performed for four differently coated AgNPs encompassing neutral, positive and negative agents used for their surface stabilization. Safety aspects were evaluated by testing interaction of AgNPs with fresh human peripheral blood mononuclear cells (hPBMC) by means of particle cellular uptake and their ability to trigger cell death, apoptosis and DNA damages through induction of oxidative stress and damages of mitochondrial membrane. Results: all tested AgNPs altered morphology of freshly isolated hPBMC inducing apoptosis and cell death in a dose- and time-dependent manner. Highest toxicity was observed for positively-charged and protein-coated AgNPs. Cellular uptake of AgNPs was also dose-dependently increased and highest for positively charged AgNPs. Intracellularly, AgNPs induced production of reactive oxygen species (ROS) and damaged mitochondrial membrane. Depending on the dose, all AgNPs exhibited genotoxic potential. Conclusions: this study provides systematic and comprehensive data showing how differently functionalized AgNPs may affect the human immune system. Presented results are a valuable scientific contribution to safety assessment of nanosilver-based blood-contacting medical products.

Background/Aims: Immune responses are involved in arterial hypertension. An observational cross-sectional case control study was conducted to estimate the association between Toll-like receptor 4 (TLR4) expression and interleukin (IL)-17A serum levels in patients with controlled and non-controlled hypertension. Methods: We have enrolled 105 non-complicated otherwise healthy hypertensive patients: 53 with well-controlled blood pressure and 52 non-controlled. TLR4 peripheral monocytes expression and serum IL-17A levels were determined by flow cytometry and ELISA, respectively. Results: Non-controlled patients exhibited higher TLR4 expression than well-controlled (25.60 vs. 21.99, P=0.011). TLR4 expression was lower in well-controlled patients who were prescribed beta blockers (18.9 vs. 22.6, P=0.005) and IL-17A concentration was higher in patients using diuretics in either group (1.41 vs. 2.01 pg/ml, P<0.001; well-controlled 1.3 vs. 1.8 pg/ml, P= 0.023; non-controlled 1.6 vs. 2.3 pg/ml, P=0.001). Correlation between IL-17A concentration and hypertension duration was observed in non-controlled patients (Spearman correlation coefficient . ρ=0.566, P<0.001) whereas in well-controlled patients a correlation was found between hypertension duration and TLR4 expression (ρ=0.322, P=0.020). Conclusions: Arterial hypertension stimulates the immune response regardless of blood pressure regulation status. Prolonged hypertension influences peripheral monocyte TLR4 expression and IL-17A serum levels. Anti-hypertensive drugs have different immunomodulatory effects: diuretics are associated with higher IL-17A concentration and beta-blockers with lower TLR4 expression.

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The interaction of silver nanoparticles (AgNPs) with the immune system has not yet been sufficiently elucidated even though they belong to the most investigated and exploited group of nanomaterials. This study aimed to evaluate immunomodulatory effect of four different AgNPs on human peripheral blood mononuclear cells (hPBMCs). Fresh hPBMCs were exposed to the small sized (~ 10 nm) AgNPs immediately after isolation from the whole blood of healthy volunteers. The study considered coating-, time-and dose-dependent response of hPBMSc and stimulation of both early and intermediate activation of lymphocytes and monocytes using flow cytometry. The AgNPs differed in surface charge and were stabilised with polyvinyl pyrrolidone (PVP), poly-L-lysine (PLL), bis(2-ethylhexyl) sulfosuccinate sodium (AOT) or blood serum albumin (BSA). Response of hPBMCs to coating agents and ionic Ag form was evaluated to distinguish their effect from the AgNPs action as they may be released from the nanosurface. There was no significant effect of any tested AgNPs on relative count of hPBMCs subpopulations. The T-cells and monocytes were not activated after treatment with AgNPs, but the highest concentration of PLL-and BSA-AgNPs decreased density of CD4 and CD8 markers on T-helper and T-cytotoxic cells, respectively. The same AgNPs activated B-and NK-cells. Ionic Ag activated T-, B-and NK-cells, but at very higher concentration, whereas only PLL exhibited immunomodulatory activity. This study evidenced immunomodulatory activity of AgNPs that may be fine-tuned by the design of their surface functionalization.