Nanotechnology is being increasingly utilised in medicine as diagnostics and for drug delivery and targeting. The small size and high surface area of nanoparticles (NPs), desirable properties that allow them to cross biological barriers, also offer potential for interaction with other cells and blood constituents, presenting possible safety risks. While NPs investigated are predominantly based on the biodegradable, biocompatible, and FDA approved poly-lactide-co-glycolide (PLGA) polymers, pro-aggregatory and antiplatelet effects have been reported for certain NPs. The potential for toxicity of PLGA based NPs remains to be examined. The aims of this study were to determine the impact of size-selected PLGA-PEG (PLGA-polyethylene glycol) NPs on platelet activation and aggregation. PLGA-PEG NPs of three average sizes of 112, 348, and 576 nm were formulated and their effect at concentrations of 0.0–2.2 mg/mL on the activation and aggregation of washed human platelets (WP) was examined. The results of this study show, for the first time, NPs of all sizes associated with the surface of platelets, with >50% binding, leading to possible internalisation. The NP-platelet interaction, however, did not lead to platelet aggregation nor inhibited aggregation of platelets induced by thrombin. The outcome of this study is promising, suggesting that these NPs could be potential carriers for targeted drug delivery to platelets.

Purpose of the Study. Antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is a rare multisystem autoimmune condition with an incidence of 0.4–24 per 1 million person- years. The severity of renal involvement predicts prognosis. Limited data are available on its management and outcomes; thus, we aim to assess this at our tertiary-care renal facility. Study Design. Retrospective data were collected using our national renal electronic database (eMED) to identify AAV patients over a period of 6 years. Outcomes included progression to end-stage renal disease (ESRD) or death, chronic kidney disease (CKD), and preservation of renal function. Results. Thirty-six patients were included in the final study. Cyclophosphamide was used in 24 patients (66.7%) and, comparatively, rituximab in 7 patients (19.4%) for induction. Seven patients (19.4%) had a documented relapse, and six patients (85.7%) had rituximab as induction therapy for relapse. The majority of patients were on azathioprine (61.1%, 57.1% relapse population) as maintenance therapy. Progression to ESRD occurred in 11 (30.6%), death in 4 (11.1%), established CKD in 15 (41.7%), and preservation of renal function in 6 (16.7%) patients by the end of the follow-up period. Conclusions. While cyclophosphamide remains the choice of induction immunosuppression therapy, we favour rituximab as an induction agent in the relapse of AAV. Despite aggressive immunosuppression therapy, the incidence of ESRD and death remains high in these patients.

Introduction: Doxorubicin (DOX) is an anthracycline that is used for a wide range of malignant conditions. However its off-target effect causes cardiotoxicity. Dexrazoxane (DEX) is the only clinically approved cardioprotective agent against anthracycline toxicity. Its activity has been attributed to its iron-chelating effects. The aim of this project was to assess the protective effect of DEX against DOXinduced toxicity in an HL-1 cardiomyocyte model, and to investigate an early stage marker involved in cellular damage by DOX. Methods: HL-1 cardiomyocytes were cultured for the purpose of bioactivity studies. The half maximal inhibitory concentration (IC-50) of DOX was established. Then the ability of DEX to recover damaged cells was assessed using measures of cell viability. A variety of DEX concentrations with HL-1 s were studied in vitro. Finally, an early stage marker involved in cellular damage by DOX was examined. An assay kit was used for the study of dsDNA breaks through the detection of γ-H2AX -a phosphorylated histone historically proven as a highly specific and sensitive molecular marker for dsDNA damage detection. Results: The IC-50 of DOX was 3 μM. When DEX was combined, there was an additional toxic effect on HL-1 s. The inhibitory effect of DEX on cell viability ceased at 10 μM. The γ-H2AX assay showed decreased dsDNA breaks in cells treated with DEX compared with those treated with DOX alone. The dsDNA breaks were increased in cells treated with DOX alone compared with control (cells alone) (P < 0.05), and dsDNA breaks were increased in cells treated with DOX alone versus those treated with combined DOX and DEX (P < 0.05). Discussion: DEX was found to abolish the DNA damage signal γ-H2AX caused by DOX in HL-1 s as demonstrated in the γ-H2AX assay, suggesting an alternative mechanism of cardioprotective action of DEX.

Conclusions: ANCA vasculitis is associated with a high risk of certain types of cardiovascular events, particularly in the early period following diagnosis.

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