Jana Semberova

Carbon nanotubes activate blood platelets by inducing extracellular Ca2+ influx sensitive to calcium entry inhibitors.

To elucidate a mechanism of prothrombotic effects of carbon nanotubes (CNTs), we report here that multiwalled CNTs activate blood platelets by inducing extracellular Ca(2+) influx that could be inhibited by calcium channel blockers SKF 96365 and 2-APB. We also demonstrate platelet aggregating activity of different single-walled and multiwalled CNTs. In addition, we show that CNT-induced platelet activation is associated with a marked release of platelet membrane microparticles positive for the granular secretion markers CD62P and CD63.

Carbon nanotubes activate store-operated calcium entry in human blood platelets.

Carbon nanotubes (CNTs) are known to potentiate arterial thrombosis in animal models, which raises serious safety issues concerning environmental or occupational exposure to CNTs and their use in various biomedical applications. We have shown previously that different CNTs, but not fullerene (nC60), induce the aggregation of human blood platelets. To date, however, a mechanism of potentially thrombogenic CNT-induced platelet activation has not been elucidated. Here we show that pristine multiwalled CNTs (MWCNTs) penetrate platelet plasma membrane without any discernible damage but interact with the dense tubular system (DTS) causing depletion of platelet intracellular Ca(2+) stores. This process is accompanied by the clustering of stromal interaction molecule 1 (STIM1) colocalized with Orai1, indicating the activation of store-operated Ca(2+) entry (SOCE). Our findings reveal the molecular mechanism of CNT-induced platelet activation which is critical in the evaluation of the biocompatibility of carbon nanomaterials with blood.

Spontaneous Closure of Patent Ductus Arteriosus in Infants ≤1500 g

Spontaneous PDA closure in VLBW infants is extremely prevalent. Infants born <26 weeks and 750 g, respectively, have a significantly higher rate of PDA at hospital discharge. OBJECTIVES: Patent ductus arteriosus (PDA) remains a challenging issue in very low birth weight (VLBW) infants, and its management varies widely. Our aim in this study was to document the natural course of ductus arteriosus in a cohort of VLBW infants who underwent conservative PDA management with no medical or surgical intervention. METHODS: A retrospective cohort study conducted in 2 European level-3 neonatal units. RESULTS: A total of 368 VLBW infants were born within the study period. Two hundred and ninety-seven infants were free of congenital malformations or heart defects and survived to hospital discharge. Out of those, 280 infants received truly conservative PDA management. In 237 (85%) of nontreated infants, the PDA closed before hospital discharge. The Kaplan-Meier model was used to document the incidence proportion of PDA closure over time for different gestational age groups. The median time to ductal closure was 71, 13, 8, and 6 days in <26+0, 26+0 to 27+6, 28+0 to 29+6, and ≥30 weeks, respectively. For different birth weight groups, the median was 48, 22, 9, and 8 days in infants weighing <750, 750 to 999, 1000 to 1249, and 1250 to 1500 g, respectively. No statistically significant relationship was found between PDA closure before hospital discharge and neonatal morbidities. CONCLUSIONS: The likelihood of PDA spontaneous closure in VLBW infants is extremely high. We provide in our findings a platform for future placebo-controlled trials focused on the smallest and youngest infants.

Noninvasive continuous cardiac output and cerebral perfusion monitoring in term infants with neonatal encephalopathy: assessment of feasibility and reliability

BackgroundNoninvasive hemodynamic monitoring of infants with neonatal encephalopathy (NE) undergoing therapeutic hypothermia (TH) would be a potentially useful clinical tool. We aimed to assess the feasibility and reliability of noninvasive cardiac output monitoring (NICOM) and near-infrared spectroscopy (NIRS) in this cohort.MethodsNICOM and NIRS were commenced to measure cardiac output (CO), systemic vascular resistance (SVR), blood pressure (BP), and cerebral regional oxygen saturations (SctO2) during TH and rewarming. NICOM measures of CO were also compared with simultaneous echocardiography-derived CO (echo-CO).ResultsTwenty infants with a median gestation of 40 weeks were enrolled. There was a strong correlation between NICOM- and echo-CO (r2=0.79, P<0.001). NICOM-CO was systematically lower than echo-CO with a bias of 27% (limits of agreement 3–51%). NICOM illustrated lower CO during TH, which increased during rewarming. SctO2 increased over the first 30 h of TH and stayed high for the remainder of the study. There was a rise in SVR over the first 30 h of TH and a decrease during rewarming (all P<0.05).ConclusionsNoninvasive hemodynamic assessment of infants with NE is feasible and illustrates potentially important changes. Larger studies are needed to assess the clinical applicability of those methods in this cohort.