Graphene, a two-dimensional monocrystalline layer of carbon atoms, has potential in many applications not only in material sciences, but also in the biomedical fields, but there is little information about the role of surface modification on the toxicity of graphene-based nanomaterials. Here, we evaluated the role of surface functionalization of the graphene nanoplatelets (GNPs) on the pulmonary inflammogenicity and translocation into mediastinal lymph nodes using a rat intratracheal instillation model. Six types of GNPs were used: All types of GNPs were based on the pristine GNPs (GNP), and different functional groups were conjugated onto them including a COOH (GNP), COH [Formula: see text], N-H [Formula: see text], F (GNP), and N=H [Formula: see text]. All types of GNPs showed very high potential for the generation of reactive oxygen species (ROS) in a dose-dependent manner when measured by a 2'7'-dichlorofluorescin diacetate assay. GNPs were instilled into the lungs of rats at 0.3 and 1 mg/rat for the evaluation of acute (24 h) inflammation and at 3 mg/rat for chronic (1 and 4 weeks) inflammation. At 24 h after instillation, all types of GNPs showed good dose-dependent increases in polymorphonuclear leukocytes with a clear dose-dependency although significant increases compared to vehicle control were found only in positively charged GNPs [Formula: see text]. While the acute inflammation in all treatment groups was returned to control levels at 1 and 4 weeks after instillation, GNPs showed similar patterns of translocation into the mediastinal lymph nodes with a higher degree over time. This study implies that the main factors of GNPs for producing lung inflammation are the potential for ROS generation and surface charge. In addition, functional groups on the GNPs might not play an important role in the extrapulmonary translocation into the mediastinal lymph nodes.
Zinc oxide nanoparticles (ZnO NPs) have many biomedical applications such as chemotherapy agents, vaccine adjuvants, and biosensors but its hemocompatibility is still poorly understood, especially in the event of direct contact of NPs with blood components. Here, we investigated the impact of size and surface functional groups on the platelet homeostasis. ZnO NPs were synthesized in two different sizes (20 and 100 nm) and with three different functional surface groups (pristine, citrate, and L-serine). ZnO NPs were incubated with plasma collected from healthy rats to evaluate the coagulation time, kinetics of thrombin generation, and profile of levels of coagulation factors in the supernatant and coronated onto the ZnO NPs. Measurements of plasma coagulation time showed that all types of ZnO NPs prolonged both active partial thromboplastin time and prothrombin time in a dose-dependent manner but there was no size- or surface functionalization-specific pattern. The kinetics data of thrombin generation showed that ZnO NPs reduced the thrombin generation potential with functionalization-specificity in the order of pristine > citrate > L-serine but there was no size-specificity. The profile of levels of coagulation factors in the supernatant and coronated onto the ZnO NPs after incubation of platelet-poor plasma with ZnO NPs showed that ZnO NPs reduced the levels of coagulation factors in the supernatant with functionalization-specificity. Interestingly, the pattern of coagulation factors in the supernatant was consistent with the levels of coagulation factors adsorbed onto the NPs, which might imply that ZnO NPs simply adsorb coagulation factors rather than stimulating these factors. The reduced levels of coagulation factors in the supernatant were consistent with the delayed coagulation time and reduced potential for thrombin generation, which imply that the adsorbed coagulation factors are not functional.
Background: Patients with major burns require replacement of intravascular volume. Hydroxyethyl starch (HES) solutions are widely used to replace intravascular volume. Dilution with crystalloids or colloids and corresponding platelet dysfunction are known causes of perioperative bleeding tendencies. The aim of the current study was to evaluate the effect of crystalloid and colloid solutions on platelet function in patients with major burns.Methods: Forty patients scheduled for burn surgery were divided into 4 groups. The infusion was started with a Hartman solution infusion (group 1) from 7 A.M. until surgery. HES (6%, Voluven Ⓡ ) was infused in the following concentrations: 7 ml/kg (group 2), 10 ml/kg (group 3), and 15 ml/kg (group 4). The bleeding time (BT), prothrombin time (PT), prothrombin time international ratio (PT INR), activated partial thromboplastin time (aPTT), hemoglobin (Hb), platelet function analyzer-100 closing time (PFA CT), and platelet count (Plt) were measured.Results: Hartmann solution and HES had no significant effect on the BT, PT, PT INR, a PTT, Hb, and Plt. The post-operative PFA CT was significantly higher in group 4 than in group 3. In group 4, the PFA CT was significantly higher post-operatively compared to pre-operatively.Conclusions: The use of high dose HES may increase the risk of bleeding tendencies in burn patients.
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