Effects of Platelet-Activating Factor on Brain Microvascular Endothelial Cells.

Platelet-activating factor (PAF) is a potent phospholipid mediator that exerts various pathophysiological effects by interacting with a G protein-coupled receptor. PAF has been reported to increase the permeability of the blood-brain barrier (BBB) via incompletely characterized mechanisms. We investigated the effect of PAF on rat brain microvascular endothelial cells (RBMVEC), a critical component of the BBB. PAF produced a dose-dependent increase in cytosolic Ca2+ concentration; the effect was prevented by the PAF receptor antagonist, WEB2086. The effect of PAF on cytosolic Ca2+ was abolished in Ca2+-free saline or in the presence of L-type voltage-gated Ca2+ channel inhibitor, nifedipine, indicating that Ca2+ influx is critical for PAF-induced increase in cytosolic Ca2+. PAF produced RBMVEC depolarization; the effect was inhibited by WEB2086. In cells loaded with [(4-amino-5-methylamino-2\u27,7\u27-difluoro-fluorescein)diacetate] (DAF-FM), a nitric oxide (NO)-sensitive fluorescent dye, PAF increased the NO level; the effect was prevented by WEB2086, nifedipine or by l-NAME, an inhibitor of NO synthase. Immunocytochemistry studies indicate that PAF reduced the immunostaining of ZO-1, a tight junction-associated protein, increased F-actin fibers, and produced intercellular gaps. PAF produced a decrease in RBMVEC monolayer electrical resistance assessed with Electric Cell-Substrate Impedance Sensing (ECIS), indicative of a disruption of endothelial barrier function. In vivo studies indicate that PAF increased the BBB permeability, assessed with sodium fluorescein and Evans Blue methods, via PAF receptor-dependent mechanisms, consequent to Ca2+ influx and increased NO levels. Our studies reveal that PAF alters the BBB permeability by multiple mechanisms, which may be relevant for central nervous system (CNS) inflammatory disorders

Time series kernel similarities for predicting Paroxysmal Atrial Fibrillation from ECGs

We tackle the problem of classifying Electrocardiography (ECG) signals with the aim of predicting the onset of Paroxysmal Atrial Fibrillation (PAF). Atrial fibrillation is the most common type of arrhythmia, but in many cases PAF episodes are asymptomatic. Therefore, in order to help diagnosing PAF, it is important to design procedures for detecting and, more importantly, predicting PAF episodes. We propose a method for predicting PAF events whose first step consists of a feature extraction procedure that represents each ECG as a multi-variate time series. Successively, we design a classification framework based on kernel similarities for multi-variate time series, capable of handling missing data. We consider different approaches to perform classification in the original space of the multi-variate time series and in an embedding space, defined by the kernel similarity measure. We achieve a classification accuracy comparable with state of the art methods, with the additional advantage of detecting the PAF onset up to 15 minutes in advance

Platelet-Activating Factor-Induced Reduction in Contact Hypersensitivity Responses Is Mediated by Mast Cells via Cyclooxygenase-2-Dependent Mechanisms

Platelet-activating factor (PAF) stimulates numerous cell types via activation of the G protein-coupled PAF receptor (PAFR). PAFR activation not only induces acute proinflammatory responses, but it also induces delayed systemic immunosuppressive effects by modulating host immunity. Although enzymatic synthesis and degradation of PAF are tightly regulated, oxidative stressors, such as UVB, chemotherapy, and cigarette smoke, can generate PAF and PAF-like molecules in an unregulated fashion via the oxidation of membrane phospholipids. Recent studies have demonstrated the relevance of the mast cell (MC) PAFR in PAFR-induced systemic immunosuppression. The current study was designed to determine the exact mechanisms and mediators involved in MC PAFR-mediated systemic immunosuppression. By using a contact hypersensitivity model, the MC PAFR was not only found to be necessary, but also sufficient to mediate the immunosuppressive effects of systemic PAF. Furthermore, activation of the MC PAFR induces MC-derived histamine and PGE2 release. Importantly, PAFR-mediated systemic immunosuppression was defective in mice that lacked MCs, or in MC-deficient mice transplanted with histidine decarboxylase- or cyclooxygenase-2-deficient MCs. Lastly, it was found that PGs could modulate MC migration to draining lymph nodes. These results support the hypothesis that MC PAFR activation promotes the immunosuppressive effects of PAF in part through histamine- and PGE2-dependent mechanisms

Observing Pulsars with a Phased Array Feed at the Parkes Telescope

During February 2016, CSIRO Astronomy and Space Science and the Max-Planck-Institute for Radio Astronomy installed, commissioned and carried out science observations with a phased array feed (PAF) receiver system on the 64m diameter Parkes radio telescope. Here we demonstrate that the PAF can be used for pulsar observations and we highlight some unique capabilities. We demonstrate that the pulse profiles obtained using the PAF can be calibrated and that multiple pulsars can be simultaneously observed. Significantly, we find that an intrinsic polarisation leakage of -31dB can be achieved with a PAF beam offset from the centre of the field of view. We discuss the possibilities for using a PAF for future pulsar observations and for searching for fast radio bursts with the Parkes and Effelsberg telescopes.Comment: 10 pages, 8 figures, 2 tables. It has been accepted for publication in PAS

Is it necessary to measure all brain regions for the assessment of PAF?

From decades of research, electroencephalography (EEG) has been proved as a potential non-invasive medical technique to measure the electrophysiological activities of brain. Alpha is one of the most prominent frequency bands of EEG because of its applications in cognitive enhancement and biofeedback methods. 300 participants were included in the present study to investigate the relationships between their cognitive performance and Peak Alpha Frequency (PAF). Brain activity was recorded from all significant brain regions in 250 participants and only from occipital region in 50 participants. The aim of the present study was to ensure the brain region which is the most dominant one to measure PAF/ IAF. Power Spectrum Density (PSD) method was used for EEG signal analysis. Interrelationship among PAF, IAF and PAF of six individual electrode positions was also explored. Findings reveled that parieto- occipital electrode points are sufficient to assess one’s peak alpha frequency

One year of monitoring the Vela pulsar using a Phased Array Feed

We have observed the Vela pulsar for one year using a Phased Array Feed (PAF) receiver on the 12-metre antenna of the Parkes Test-Bed Facility. These observations have allowed us to investigate the stability of the PAF beam-weights over time, to demonstrate that pulsars can be timed over long periods using PAF technology and to detect and study the most recent glitch event that occurred on 12 December 2016. The beam-weights are shown to be stable to 1% on time scales on the order of three weeks. We discuss the implications of this for monitoring pulsars using PAFs on single dish telescopes.Comment: 6 pages, 4 figures, 2 tables. Accepted for publication in PAS

Permanent atrial fibrillation ablation surgery in patients with advanced age

Background: Even if permanent atrial fibrillation (pAF) is a frequent concomitant problem in patients undergoing open heart surgery and particularly in those with advanced age, data of pAF ablation surgery in older aged patients are scarce. This study was performed to assess early and late results of combined open heart surgery and pAF ablation procedures in patients with advanced aged, compared to young patients. Material and Methods: A selective group of 126 patients (Group A: age ≥70 [76.4±4.8] years, n=70; Group B: age <70 [62.0±6.2] years: n=56) with pAF (≥6 months) underwent either monopolar (Group A, B: n=51 vs. n=44) or bipolar (Group A, B: n=19 vs. n=12) radiofrequency (RF) ablation procedures concomitant to open heart surgery. Regular follow-up was performed 3 to 36 months after surgery to assess survival, New York Heart Association (NYHA) class and conversion rate to stable sinus rhythm (SR). Results: Early mortality (<30 days) was 2.9% in Group A (Group B: 0%), cumulative survival at long-term follow up was 0.78 vs. 0.98 (p=0.03) and NYHA-class improved significantly in both groups, particularly in cases with stable SR. At 12-months follow-up 73% of Group A patients were in stable SR (Group B 78%). Conclusions: Concomitant mono- and bipolar RF ablation surgery represents a safe option to cure pAF during open heart surgery with a very low risk, even in patients with advanced age

The effect of lipoprotein-associated phospholipase A2 deficiency on pulmonary allergic responses in Aspergillus fumigatus sensitized mice.

BackgroundLipoprotein-associated phospholipase A2 (Lp-PLA2)/platelet-activating factor acetylhydrolase (PAF-AH) has been implicated in the pathogenesis of cardiovascular disease. A therapeutic targeting of this enzyme was challenged by the concern that increased circulating platelet activating factor (PAF) may predispose to or increase the severity of the allergic airway response. The aim of this study was to investigate whether Lp-PLA2 gene deficiency increases the risk of PAF and IgE-mediated inflammatory responses in vitro and in vivo using mouse models.MethodsLp-PLA2-/- mice were generated and back crossed to the C57BL/6 background. PAF-AH activity was measured using a hydrolysis assay in serum and bronchoalveolar lavage (BAL) samples obtained from mice. Aspergillus fumigatus (Af)-specific serum was prepared for passive allergic sensitization of mice in vivo and mast cells in vitro. β- hexosaminidase release was studied in bone marrow derived mast cells sensitized with Af-specific serum or DNP-IgE and challenged with Af or DNP, respectively. Mice were treated with lipopolysaccharide (LPS) and PAF intratracheally and studied 24 hours later. Mice were sensitized either passively or actively against Af and were studied 48 hours after a single intranasal Af challenge. Airway responsiveness to methacholine, inflammatory cell influx in the lung tissue and BAL, immunoglobulin (ELISA) and cytokine (Luminex) profiles were compared between the wild type (WT) and Lp-PLA2-/- mice.ResultsPAF-AH activity was reduced but not completely abolished in Lp-PLA2-/- serum or by in vitro treatment of serum samples with a high saturating concentration of the selective Lp-PLA2 inhibitor, SB-435495. PAF inhalation significantly enhanced airway inflammation of LPS treated WT and Lp-PLA2-/- mice to a similar extent. Sensitized WT and Lp-PLA2-/- bone-marrow derived mast cells released β-hexosaminidase following stimulation by allergen or IgE crosslinking to equivalent levels. Wild type and Lp-PLA2-/- mice responded to passive or active allergic sensitization by significant IgE production, airway inflammation and hyperresponsiveness after Af challenge. BAL cell influx was not different between these strains while IL-4, IL-5, IL-6 and eotaxin release was attenuated in Lp-PLA2-/- mice. There were no differences in the amount of total IgE levels in the Af sensitized WT and Lp-PLA2-/- mice.ConclusionsWe conclude that Lp-PLA2 deficiency in C57BL/6 mice did not result in a heightened airway inflammation or hyperresponsiveness after PAF/LPS treatment or passive or active allergic sensitization and challenge