Silver nanoparticles promote the emergence of heterogeneic human neutrophil sub-populations

Neutrophil surveillance is central to nanoparticle clearance. Silver nanoparticles (AgNP) have numerous uses, however conflicting evidence exists as to their impact on neutrophils and whether they trigger damaging inflammation. Neutrophil’s importance in innate defence and regulating immune networks mean it’s essential we understand AgNP’s impact on neutrophil function. Human neutrophil viability following AgNP or Ag Bulk treatment was analysed by flow cytometry and AnV/PI staining. Whilst AgNP exposure did not increase the total number of apoptotic neutrophils, the number of late apoptotic neutrophils was increased, suggesting AgNP increase transit through apoptosis. Mature (CD16bright/CD62Lbright), immature (CD16dim/CD62Lbright) and apoptotic (CD16dim/CD62Ldim) neutrophil populations were evident within isolated neutrophil preparations. AgNP exposure significantly reduced CD62L staining of CD16bright/CD62Lbright neutrophils, and increased CD16 staining of CD16dim/CD62Lbright populations, suggesting AgNPs trigger neutrophil activation and maturation, respectively. AgNP exposure dramatically increased IL-8, yet not classical pro-inflammatory cytokine release, suggesting AgNP triggers neutrophil activation, without pro-inflammation or damaging, necrotic cell death. For the first time, we show AgNPs differentially affect distinct sub-populations of circulating human neutrophils; activating mature neutrophils with the emergence of CD16bright/CD62Ldim neutrophils. This may stimulate particle clearance without harmful inflammation, challenging previous assumptions that silver nanomaterials induce neutrophil toxicity and damaging inflammatory responses

A single bout of hybrid intradialytic exercise did not affect left-ventricular function in exercise-naïve dialysis patients: a randomized, cross-over trial.

INTRODUCTION: Cardiovascular diseases are the leading cause of mortality in end-stage renal disease (ESRD) patients, especially those receiving hemodialysis (HD) therapy. HD has many side effects that are related to patients' hearts, such as recurrent myocardial ischemia and global or segmental left-ventricular dysfunction, which is associated with intradialytic hypotension, long-term loss of systolic function, and high incidence of cardiovascular events and death. Systematic exercise training has a beneficial effect on measures of cardiovascular fitness and reducing cardiovascular risk factors in ESRD. Whether there is an acute benefit of exercise during HD on left-ventricular function is not well known. The current study aimed to investigate whether a single bout of hybrid (aerobic and resistance) intradialytic exercise could affect left-ventricular function during HD sessions. METHODS: Twenty-one exercise naïve and clinically stable HD patients participated in the study. All participants completed two different HD trials on two different days, separated by 1 week: (1) standard HD and (2) HD including a single bout of hybrid intradialytic exercise. Hybrid intradialytic training included the usual intradialytic cycling followed by resistance training using elastic bands and dumbbells. Echocardiographic assessment of left-ventricular function was completed before HD, half an hour before the end of HD, and 30 min after the end of HD. RESULTS: Cohort data for left-ventricular function indices were not different between trials and did not change across time in either the standard HD or HD plus exercise trial. Cohort data for the change in ejection fraction from baseline to during HD did mask considerable inter-individual variability (HD - 0 ± 15; HD plus exercise (- 2 ± 20). Despite this, the variability was not mediated by the addition of intradialytic hybrid exercise. CONCLUSION: A single bout of hybrid intradialytic exercise did not affect left-ventricular function during the HD therapy. It is important to determine whether chronic exercise training could beneficially affect left-ventricular function abnormalities often observed during the HD therapy. TRIAL REGISTRATION NUMBER: The study is registered at ClinicalTrials.gov (NCT01721551) as a clinical trial