Concern about the use of nanomaterials has increased significantly in recent years due to potentially hazardous impacts on human health. Mast cells are critical for innate and adaptive immune responses, often modulating allergic and pathogenic conditions. Mast cells are well known to act in response to danger signals through a variety of receptors and pathways including IL-33 and the IL-1 like receptor ST2. Here, we examined the involvement of mast cells and the IL-33/ST2 axis in the pulmonary and cardiovascular responses to MWCNT exposure. The toxicological effects of MWCNTs were observed only in mice with a sufficient population of mast cells and were not observed when mast cells were absent or incapable of responding to IL-33. Our findings establish for the first time that mast cells and the IL-33/ST2 axis orchestrate adverse pulmonary and cardiovascular responses to an engineered nanomaterial, giving insight into a previously unknown mechanism of toxicity. This novel mechanism of toxicity could be used for assessing the safety of engineered nanomaterials and provides a realistic therapeutic target for potential nanoparticle induced toxicities.

In subjects with symptomatic PAD, elevated baseline DD, a marker of thrombotic activity, was significantly associated with the occurrence of myocardial infarction. This study did not confirm a relationship between progression of PAD and baseline DD or CRP during the first 3 years. Baseline DD and CRP do not provide useful risk stratification in patients at high risk for progression of symptomatic PAD. Future studies should evaluate serial levels of these markers to assess their utility in predicting progression of symptomatic PAD.

BackgroundThe exceptional physical-chemical properties of carbon nanotubes have lead to their use in diverse commercial and biomedical applications. However, their utilization has raised concerns about human exposure that may predispose individuals to adverse health risks. The present study investigated the susceptibility to cardiac ischemic injury following a single exposure to various forms of multi-walled carbon nanotubes (MWCNTs). It was hypothesized that oropharyngeal aspiration of MWCNTs exacerbates myocardial ischemia and reperfusion injury (I/R injury).MethodsOropharyngeal aspiration was performed on male C57BL/6J mice with a single amount of MWCNT (0.01 - 100 μg) suspended in 100 μL of a surfactant saline (SS) solution. Three forms of MWCNTs were used in this study: unmodified, commercial grade (C-grade), and functionalized forms that were modified either by acid treatment (carboxylated, COOH) or nitrogenation (N-doped) and a SS vehicle. The pulmonary inflammation, serum cytokine profile and cardiac ischemic/reperfusion (I/R) injury were assessed at 1, 7 and 28 days post-aspiration.ResultsPulmonary response to MWCNT oropharyngeal aspiration assessed by bronchoalveolar lavage fluid (BALF) revealed modest increases in protein and inflammatory cell recruitment. Lung histology showed modest tissue inflammation as compared to the SS group. Serum levels of eotaxin were significantly elevated in the carboxylated MWCNT aspirated mice 1 day post exposure. Oropharyngeal aspiration of all three forms of MWCNTs resulted in a time and/or dose-dependent exacerbation of myocardial infarction. The severity of myocardial injury varied with the form of MWCNTs used. The N-doped MWCNT produced the greatest expansion of the infarct at any time point and required a log concentration lower to establish a no effect level. The expansion of the I/R injury remained significantly elevated at 28 days following aspiration of the COOH and N-doped forms, but not the C-grade as compared to SS.ConclusionOur results suggest that oropharyngeal aspiration of MWCNT promotes increased susceptibility of cardiac tissue to ischemia/reperfusion injury without a significant pulmonary inflammatory response. The cardiac injury effects were observed at low concentrations of MWCNTs and presence of MWCNTs may pose a significant risk to the cardiovascular system.

Lower extremity DVT is common in critically ill trauma patients, particularly in the first week following injury, regardless of injury pattern, DVT risk factors, or pharmacologic prophylaxis. Previous studies have underestimated DVT rates by not investigating CVDVTs and not exclusively targeting critically ill patients. We recommend early and continued DUS DVT screening of all critically ill trauma patients.

The potential uses of engineered C₆₀ fullerene (C₆₀) have expanded in recent decades to include industrial and biomedical applications. Based on clinical findings associated with particulate matter exposure and our data with multi-walled carbon nanotubes, we hypothesized that ischemia/reperfusion (I/R) injury and pharmacological responses in isolated coronary arteries would depend upon the route of exposure and gender in rats instilled with C₆₀. Male and female Sprague Dawley rats were used to test this hypothesis by surgical induction of cardiac I/R injury in situ 24 h after intratracheal (IT) or intravenous (IV) instillation of 28 μg of C₆₀ formulated in polyvinylpyrrolidone (PVP) or PVP vehicle. Serum was collected for quantification of various cytokines. Coronary artery segments were isolated for assessment of vasoactive pharmacology via wire myography. Both IV and IT exposure to C₆₀ resulted in expansion of myocardial infarction in male and female rats following I/R injury. Serum-collected post-I/R showed elevated concentrations of interleukin-6 and monocyte chemotactic protein-1 in male rats exposed to IV C₆₀. Coronary arteries isolated from male rats exposed to IT C₆₀ demonstrated augmented vasocontraction in response to endothelin-1 that was attenuated with Indomethacin. IV C₆₀ exposure resulted in impaired acetylcholine relaxation in male rats and IT C₆₀ exposure resulted in depressed vasorelaxation in response to sodium nitroprusside in female rats. Based on these data, we conclude that IT and IV exposure to C₆₀ results in unique cardiovascular consequences that may favor heightened coronary resistance and myocardial susceptibility to I/R injury.