Shape matters: effects of silver nanospheres and wires on human alveolar epithelial cells

<p>Abstract</p> <p>Background</p> <p>In nanotoxicology, the exact role of particle shape, in relation to the composition, on the capacity to induce toxicity is largely unknown. We investigated the toxic and immunotoxic effects of silver wires (length: 1.5 - 25 μm; diameter 100 - 160 nm), spherical silver nanoparticles (30 nm) and silver microparticles (<45 μm) on alveolar epithelial cells (A549).</p> <p>Methods</p> <p>Wires and nanoparticles were synthesized by wet-chemistry methods and extensively characterized. Cell viability and cytotoxicity were assessed and potential immunotoxic effects were investigated. To compare the effects on an activated and a resting immune system, cells were stimulated with rhTNF-α or left untreated. Changes in intracellular free calcium levels were determined using calcium imaging. Finally, ion release from the particles was assessed by ICP-MS and the effects of released ions on cell viability and cytotoxicity were tested.</p> <p>Results</p> <p>No effects were observed for the spherical particles, whereas the silver wires significantly reduced cell viability and increased LDH release from A549 cells. Cytokine promoter induction and NF-κB activation decreased in a concentration dependent manner similar to the decrease seen in cell viability. In addition, a strong increase of intracellular calcium levels within minutes after addition of wires was observed. This toxicity was not due to free silver ions, since the samples with the highest ion release did not induce toxicity and ion release control experiments with cells treated with pre-incubated medium did not show any effects either.</p> <p>Conclusions</p> <p>These data showed that silver wires strongly affect the alveolar epithelial cells, whereas spherical silver particles had no effect. This supports the hypothesis that shape is one of the important factors that determine particle toxicity.</p

Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats

<p>Abstract</p> <p>Background</p> <p>Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs) following inhalation of UfCPs (24 h, 172 μg·m^-3), to assess whether compromised animals (SHR) exhibit a different response pattern compared to the previously studied healthy rats (WKY).</p> <p>Methods</p> <p>Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP) and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1), blood coagulation (tissue factor, plasminogen activator inhibitor-1), and endothelial function (endothelin-1, and endothelin receptors A and B) were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF).</p> <p>Results</p> <p>Increased BP and heart rate (HR) by about 5% with a lag of 1–3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary) and blood (systemic) were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p < 0.05) with endothelin 1 being the maximally induced factor (6-fold; p < 0.05) on the third recovery day in the lungs of UfCPs exposed SHRs; while all of these factors – except hemeoxygenase-1 – were not affected in cardiac tissues. Strikingly, the UfCPs-mediated altered BP is paralleled by the induction of renin-angiotensin system in plasma.</p> <p>Conclusion</p> <p>Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction, stimulation of blood coagulation factors, and inhibition of fibrinolysis. Thus, UfCPs may cause cardiovascular and pulmonary impairment, in the absence of detectable pulmonary inflammation, in individuals suffering from preexisting cardiovascular diseases.</p

Surface thermodynamics and kinetics from first principles

info:eu-repo/semantics/nonPublishe

Shape matters : Effects of silver nanospheres and wires on human alveolar epithelial cells

Background: In nanotoxicology, the exact role of particle shape, in relation to the composition, on the capacity to induce toxicity is largely unknown. We investigated the toxic and immunotoxic effects of silver wires (length: 1.5 - 25 μm; diameter 100 - 160 nm), spherical silver nanoparticles (30 nm) and silver microparticles (<45 μm) on alveolar epithelial cells (A549).Methods: Wires and nanoparticles were synthesized by wet-chemistry methods and extensively characterized. Cell viability and cytotoxicity were assessed and potential immunotoxic effects were investigated. To compare the effects on an activated and a resting immune system, cells were stimulated with rhTNF-α or left untreated. Changes in intracellular free calcium levels were determined using calcium imaging. Finally, ion release from the particles was assessed by ICP-MS and the effects of released ions on cell viability and cytotoxicity were tested.Results: No effects were observed for the spherical particles, whereas the silver wires significantly reduced cell viability and increased LDH release from A549 cells. Cytokine promoter induction and NF-κB activation decreased in a concentration dependent manner similar to the decrease seen in cell viability. In addition, a strong increase of intracellular calcium levels within minutes after addition of wires was observed. This toxicity was not due to free silver ions, since the samples with the highest ion release did not induce toxicity and ion release control experiments with cells treated with pre-incubated medium did not show any effects either.Conclusions: These data showed that silver wires strongly affect the alveolar epithelial cells, whereas spherical silver particles had no effect. This supports the hypothesis that shape is one of the important factors that determine particle toxicity

Maleimide-styrene-butadiene terpolymers : acrylonitrile-butadiene-styrene inspired photopolymers for additive manufacturing

The terpolymer acrylonitrile-butadiene-styrene (ABS) is a widely used thermoplastic material due to its excellent mechanical properties, especially high toughness. However, the monomer system of ABS cannot be feasibly photopolymerized due to its reactivity, opacity and monomer volatility. We show the transfer of an ABS microstructure to photopolymers via monomer systems designed to mimic ABS while remaining photopolymerizable. Acrylonitrile was substituted by more reactive and less volatile maleimides, of which the N substituent influences crosslinking considerably. Instead of styrene, less volatile derivatives were utilized as comonomers. Poly(butadiene) was introduced as cheap, readily available and non-volatile rubber. The resulting maleimide-styrene-poly(butadiene) networks exhibit varying microphase separations and simultaneous transparency. While optimized materials cannot quite exhibit the yield strain of hot-pressed ABS filament, their toughness partly exceeds that of ABS. Superior thermal stabilities and glass transition temperatures up to 190 °C were observed. Finally, stereolithographic printing of one tuned monomer system was conducted.</p

Materials / 3D Printable Biophotopolymers for in Vivo Bone Regeneration

The present study investigated two novel biophotopolymer classes that are chemically based on non-toxic poly (vinyl alcohol). These vinylesters and vinylcarbonates were compared to standard acrylates in vitro on MC3T3-E1 cells and in vivo in a small animal model. In vitro, both vinylester and vinylcarbonate monomers showed about tenfold less cytotoxicity when compared to acrylates (IC50: 2.922 mM and 2.392 mM vs. 0.201 mM) and at least threefold higher alkaline phosphatase activity (17.038 and 18.836 vs. 5.795, measured at [10 mM]). In vivo, polymerized 3D cellular structures were implanted into the distal femoral condyle of 16 New Zealand White Rabbits and were observed for periods from 4 to 12 weeks. New bone formation and bone to implant contact was evaluated by histomorphometry at end of observation. Vinylesters showed similar rates of new bone formation but significantly less (p = 0.002) bone to implant contact, when compared to acrylates. In contrast, the implantation of vinylcarbonate based biophotopolymers led to significantly higher rates of newly formed bone (p < 0.001) and bone to implant contact (p < 0.001). Additionally, distinct signs of polymer degradation could be observed in vinylesters and vinylcarbonates by histology. We conclude, that vinylesters and vinylcarbonates are promising new biophotopolymers, that outmatch available poly(lactic acid) and (meth)acrylate based materials.(VLID)490353

Selective transformations of complex molecules are enabled by aptameric protective groups

Emerging trends in drug discovery are prompting a renewed interest in natural products as a source of chemical diversity and lead structures. However, owing to the structural complexity of many natural compounds, the synthesis of derivatives is not easily realized. Here, we demonstrate a conceptually new approach using oligonucleotides as aptameric protective groups. These block several functionalities by non-covalent interactions in a complex molecule and enable the highly chemo- and regioselective derivatization (>99%) of natural antibiotics in a single synthetic step with excellent conversions of up to 83%. This technique reveals an important structure–activity relationship in neamine-based antibiotics and should help both to accelerate the discovery of new biologically active structures and to avoid potentially costly and cumbersome synthetic routes.

Adverse Events in 1406 Patients Receiving 13,780 Cycles of Azacitidine within the Austrian Registry of Hypomethylating Agents—A Prospective Cohort Study of the AGMT Study-Group

Background: Azacitidine is the treatment backbone for patients with acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia who are considered unfit for intensive chemotherapy. Detailed reports on adverse events in a real-world setting are lacking. Aims: To analyze the frequency of adverse events in the Austrian Registry of Hypomethylating agents. To compare real-world data with that of published randomized clinical trials. Results: A total of 1406 patients uniformly treated with a total of 13,780 cycles of azacitidine were analyzed. Hematologic adverse events were the most common adverse events (grade 3–4 anemia 43.4%, grade 3–4 thrombopenia 36.8%, grade 3–4 neutropenia 36.1%). Grade 3–4 anemia was significantly more common in the Registry compared to published trials. Febrile neutropenia occurred in 33.4% of patients and was also more common in the Registry than in published reports. Other commonly reported adverse events included fatigue (33.4%), pain (29.2%), pyrexia (23.5%), and injection site reactions (23.2%). Treatment termination due to an adverse event was rare (5.1%). Conclusion: The safety profile of azacitidine in clinical trials is reproducible in a real-world setting. With the use of prophylactic and concomitant medications, adverse events can be mitigated and azacitidine can be safely administered to almost all patients with few treatment discontinuations