Stabilization of Graphene Oxide Dispersion in Plasma-like Isotonic Solution Containing Aggregating Concentrations of Bivalent Cations.

Graphene oxide's (GO) intravascular applications and biocompatibility are not fully explored yet, although it has been proposed as an anticancer drug transporter, antibacterial factor or component of wearable devices. Bivalent cations and the number of particles' atom layers, as well as their structural oxygen content and pH of the dispersion, all affect the GO size, shape, dispersibility and biological effects. Bovine serum albumin (BSA), an important blood plasma protein, is expected to improve GO dispersion stability in physiological concentrations of the precipitating calcium and magnesium cations to enable effective and safe tissue perfusion. METHODS: Four types of GO commercially available aqueous dispersions (with different particle structures) were diluted, sonicated and studied in the presence of BSA and physiological cation concentrations. Nanoparticle populations sizes, electrical conductivity, zeta potential (Zetasizer NanoZS), structure (TEM and CryoTEM), functional groups content (micro titration) and dispersion pH were analyzed in consecutive preparation stages. RESULTS: BSA effectively prevented the aggregation of GO in precipitating concentrations of physiological bivalent cations. The final polydispersity indexes were reduced from 0.66-0.91 to 0.36-0.43. The GO-containing isotonic dispersions were stable with the following Z-ave results: GO1 421.1 nm, GO2 382.6 nm, GO3 440.2 nm and GO4 490.1 nm. The GO behavior was structure-dependent. CONCLUSION: BSA effectively stabilized four types of GO dispersions in an isotonic dispersion containing aggregating bivalent physiological cations.

Persistent mild lesions in coronary angiography predict poor long-term survival of heart transplant recipients.

BACKGROUND: Even though coronary angiography (CAG) underestimates coronary allograft vasculopathy (CAV) development, especially in the distal parts of arteries, it remains a frame of reference for International Society for Heart and Lung Transplantation (ISHLT) CAV classification. A retrospective analysis was performed to assess the prognostic value of CAG findings. METHODS: Among 310 orthotopic heart transplantation (OHT) recipients with at least 2 CAGs at 2-year intervals, we identified 197 (146 men and 41 women; 55 ± 13 years) without lesions (Group 0), 27 (15 men and 12 women; 58 ± 8 years) in whom mild changes remained in consecutive CAGs (Group 1), 28 (24 men and 4 women; 58 ± 10 years) in whom mild lesions decreased in consecutive CAGs (Group 1REG), and 58 (53 men and 5 women; 56 ± 10 years) in whom the stenosis criteria of ISHLT CAV 2 or 3 were covered (Group 2). We compared survival and other clinical variables among the groups. RESULTS: The average follow-up was 10 ± 4 years. Forty-one (21%) deaths occurred in Group 0, 15 (56%) in Group 1 (p = 0.002), 9(31%) in Group 1REG (p = NS), and 26 (46%) in Group 2 (p = 0.004, chi-square test). Time free from all-cause death was significantly shorter in Group 1 (T1/2 = 8 years) than in Group 0 (T1/2 = 15.5 years; p = 0.00072, log-rank test). Time free from cardiovascular death was significantly shorter in Groups 1 and 2, as was time free from CAV-related death in Groups 1, 1REG, and 2. Multivariate analysis, using a Cox proportional hazards model, revealed that Group 1 inclusion criterion of CAG findings is an independent predictor of all-cause death, cardiovascular death, and CAV-related death. CONCLUSIONS: Persistent mild coronary lesions, observed in consecutive CAG, predicted shorter survival of OHT recipients.

Influence of proliferation signal inhibitors on vascular endothelial growth factor production in heart transplant recipients - preliminary report.

Proliferation signal inhibitors (PSI) are especially beneficial for heart transplant recipients, but are rarely used due to frequent side effects. As they may be caused by vascular endothelial growth factor (VEGF), we performed a prospective cross-sectional pilot study to assess the influence of PSI and/or calcineurin inhibitors (CNI) presence in immunosuppressive protocols of heart transplant recipients on VEGF secretion. All electively screened heart transplant recipients willing to participate were enrolled in the study. The preliminary report was based on the results of the first 89 serum samples. The study group (n = 84) consisted of the PSI group (n = 14) further divided into the PSI + CNI subgroup (n = 10) and PSIw/oCNI subgroup (n = 4) based on concomitant CNI use, and the CNIw/oPSI group (n = 70) receiving CNI without PSI. The control group (n = 5) consisted of patients not requiring immunosuppression. VEGF was present in serum of 70 (83%) study group patients: median (range) 18 (0-316) pg/mL, mean 35 ± 57 pg/mL; in 13 (93%) PSI group patients: 22 (0-110) pg/mL, 28 ± 28 pg/mL, with 19 (8-20) pg/mL, 16 ± 6 pg/mL in the PSI + CNI subgroup, and 29 (0-110) pg/mL, 32 ± 32 pg/mL in the PSIw/oCNI subgroup. In the CNIw/oPSI group VEGF was present in 57 (81%) patients: 16 (0-316) pg/mL, 37 ± 62 pg/mL, and in the control group in 3 (60%) patients: 4 (0-110) pg/mL, 32 ± 48 pg/mL. None of the differences observed between any compared groups and/or subgroups was significant (χ(2) and Mann-Whitney U test). In conclusion, differences of VEGF concentration observed among groups imply the influence of PSI and CNI on VEGF production, but further studies involving higher numbers of participants are needed to prove it.