Differential modulation of ROS signals and other mitochondrial parameters by the antioxidants MitoQ, resveratrol and curcumin in human adipocytes

Abstract Mitochondrial reactive oxygen species (ROS) have been demonstrated to play an important role as signaling and regulating molecules in human adipocytes. In order to evaluate the differential modulating roles of antioxidants, we treated human adipocytes differentiated from human bone marrow-derived mesenchymal stem cells with MitoQ, resveratrol and curcumin. The effects on ROS, viability, mitochondrial respiration and intracellular ATP levels were examined. MitoQ lowered both oxidizing and reducing ROS. Resveratrol decreased reducing and curcumin oxidizing radicals only. All three substances slightly decreased state III respiration immediately after addition. After 24 h of treatment, MitoQ inhibited both basal and uncoupled oxygen consumption, whereas curcumin and resveratrol had no effect. Intracellular ATP levels were not altered. This demonstrates that MitoQ, resveratrol and curcumin exert potent modulating effects on ROS signaling in human adipocyte with marginal effects on metabolic parameters.

A multivariate approach for processing magnetization effects in triggered event-related functional magnetic resonance imaging time series

Triggered event-related functional magnetic resonance imaging requires sparse intervals of temporally resolved functional data acquisitions, whose initiation corresponds to the occurrence of an event, typically an epileptic spike in the electroencephalographic trace. However, conventional fMRI time series are greatly affected by non-steady-state magnetization effects, which obscure initial blood oxygen level-dependent (BOLD) signals. Here, conventional echo-planar imaging and a post-processing solution based on principal component analysis were employed to remove the dominant eigenimages of the time series, to filter out the global signal changes induced by magnetization decay and to recover BOLD signals starting with the first functional volume. This approach was compared with a physical solution using radiofrequency preparation, which nullifies magnetization effects. As an application of the method, the detectability of the initial transient BOLD response in the auditory cortex, which is elicited by the onset of acoustic scanner noise, was used to demonstrate that post-processing-based removal of magnetization effects allows to detect brain activity patterns identical with those obtained using the radiofrequency preparation. Using the auditory responses as an ideal experimental model of triggered brain activity, our results suggest that reducing the initial magnetization effects by removing a few principal components from fMRI data may be potentially useful in the analysis of triggered event-related echo-planar time series. The implications of this study are discussed with special caution to remaining technical limitations and the additional neurophysiological issues of the triggered acquisition.

Radiofrequency ablation in children and adolescents: results in 154 consecutive patients

AIMS: The experience of using radiofrequency ablation (RFA) for the treatment of arrhythmias in children and adolescents is still limited. This study aimed to review the most recent results of RF ablation in children and adolescents in a highly experienced centre with access to both conventional techniques and non-fluoroscopic electroanatomic mapping (CARTO). METHODS AND RESULTS: A total of 154 consecutive patients younger than 19 years treated with RFA during the period 2000-04 were included. Numbers (%) or median (quartiles) are reported. Age was 15 (12-17) years, 70 (45%) were males. Five patients (3%) had congenital heart disease. RFA was successful in 147/154 patients (95%). Arrhythmia recurrence occurred in 11 patients (7%). Procedure time was 55 (35-90) min and fluoroscopy time was 8.8 (4-19) min. Number of RF applications was 4 (2-10) and number of RF applications >20 s was 2 (1-7). One patient (0.7%) had complicating high-grade atrioventricular block. CARTO was used in 18 RF ablation procedures (11%) performed in 15 patients. CONCLUSION: RF ablation can be undertaken in children and adolescents with a high success rate, few recurrences and complications, very short procedure times, and acceptable fluoroscopy times. Non-fluoroscopic electroanatomic mapping is helpful in selected patients.

Fiberoptic system for recording dendritic calcium signals in layer 5 neocortical pyramidal cells in freely moving rats

Calcium influx into the dendritic tufts of layer 5 neocortical pyramidal neurons modifies a number of important cellular mechanisms. It can trigger local synaptic plasticity and switch the firing properties from regular to burst firing. Due to methodological limitations, our knowledge about Ca2+ spikes in the dendritic tuft stems mostly from in vitro experiments. However, it has been speculated that regenerative Ca2+ events in the distal dendrites correlate with distinct behavioral states. Therefore it would be most desirable to be able to record these Ca2+ events in vivo, preferably in the behaving animal. Here, we present a novel approach for recording Ca2+ signals in the dendrites of populations of layer 5 pyramidal neurons in vivo, which ensures that all recorded fluorescence changes are due to intracellular Ca2+ signals in the apical dendrites. The method has two main features: 1) bolus loading of layer 5 with a membrane-permeant Ca2+ dye resulting in specific loading of pyramidal cell dendrites in the upper layers and 2) a fiberoptic cable attached to a gradient index lens and a prism reflecting light horizontally at 90 degrees to the angle of the apical dendrites. We demonstrate that the in vivo signal-to-noise ratio recorded with this relatively inexpensive and easy-to-implement fiberoptic-based device is comparable to conventional camera-based imaging systems used in vitro. In addition, the device is flexible and lightweight and can be used for recording Ca2+ signals in the distal dendritic tuft of freely behaving animals.

Perceptual Learning via Modification of Cortical Top-Down Signals

The primary visual cortex (V1) is pre-wired to facilitate the extraction of behaviorally important visual features. Collinear edge detectors in V1, for instance, mutually enhance each other to improve the perception of lines against a noisy background. The same pre-wiring that facilitates line extraction, however, is detrimental when subjects have to discriminate the brightness of different line segments. How is it possible to improve in one task by unsupervised practicing, without getting worse in the other task? The classical view of perceptual learning is that practicing modulates the feedforward input stream through synaptic modifications onto or within V1. However, any rewiring of V1 would deteriorate other perceptual abilities different from the trained one. We propose a general neuronal model showing that perceptual learning can modulate top-down input to V1 in a task-specific way while feedforward and lateral pathways remain intact. Consistent with biological data, the model explains how context-dependent brightness discrimination is improved by a top-down recruitment of recurrent inhibition and a top-down induced increase of the neuronal gain within V1. Both the top-down modulation of inhibition and of neuronal gain are suggested to be universal features of cortical microcircuits which enable perceptual learning.

Automatic Reduction of Artifacts in EEG-Signals

Electroencephalograms (EEG) are often contaminated with high amplitude artifacts limiting the usability of data. Methods that reduce these artifacts are often restricted to certain types of artifacts, require manual interaction or large training data sets. Within this paper we introduce a novel method, which is able to eliminate many different types of artifacts without manual intervention. The algorithm first decomposes the signal into different sub-band signals in order to isolate different types of artifacts into specific frequency bands. After signal decomposition with principal component analysis (PCA) an adaptive threshold is applied to eliminate components with high variance corresponding to the dominant artifact activity. Our results show that the algorithm is able to significantly reduce artifacts while preserving the EEG activity. Parameters for the algorithm do not have to be identified for every patient individually making the method a good candidate for preprocessing in automatic seizure detection and prediction algorithms.

Radiofrequency electromagnetic field exposure and non-specific symptoms of ill health: A systematic review

This article is a systematic review of whether everyday exposure to radiofrequency electromagnetic field (RF-EMF) causes symptoms, and whether some individuals are able to detect low-level RF-EMF (below the ICNIRP [International Commission on Non-Ionizing Radiation Protection] guidelines). Peer-reviewed articles published before August 2007 were identified by means of a systematic literature search. Meta-analytic techniques were used to pool the results from studies investigating the ability to discriminate active from sham RF-EMF exposure. RF-EMF discrimination was investigated in seven studies including a total of 182 self-declared electromagnetic hypersensitive (EHS) individuals and 332 non-EHS individuals. The pooled correct field detection rate was 4.2% better than expected by chance (95% CI: -2.1 to 10.5). There was no evidence that EHS individuals could detect presence or absence of RF-EMF better than other persons. There was little evidence that short-term exposure to a mobile phone or base station causes symptoms based on the results of eight randomized trials investigating 194 EHS and 346 non-EHS individuals in a laboratory. Some of the trials provided evidence for the occurrence of nocebo effects. In population based studies an association between symptoms and exposure to RF-EMF in the everyday environment was repeatedly observed. This review showed that the large majority of individuals who claims to be able to detect low level RF-EMF are not able to do so under double-blind conditions. If such individuals exist, they represent a small minority and have not been identified yet. The available observational studies do not allow differentiating between biophysical from EMF and nocebo effects.

Radiological anatomy of the obturator nerve and its articular branches: basis to develop a method of radiofrequency denervation for hip joint pain

OBJECTIVE: A previous study of radiofrequency neurotomy of the articular branches of the obturator nerve for hip joint pain produced modest results. Based on an anatomical and radiological study, we sought to define a potentially more effective radiofrequency method. DESIGN: Ten cadavers were studied, four of them bilaterally. The obturator nerve and its articular branches were marked by wires. Their radiological relationship to the bone structures on fluoroscopy was imaged and analyzed. A magnetic resonance imaging (MRI) study was undertaken on 20 patients to determine the structures that would be encountered by the radiofrequency electrode during different possible percutaneous approaches. RESULTS: The articular branches of the obturator nerve vary in location over a wide area. The previously described method of denervating the hip joint did not take this variation into account. Moreover, it approached the nerves perpendicularly. Because optimal coagulation requires electrodes to lie parallel to the nerves, a perpendicular approach probably produced only a minimal lesion. In addition, MRI demonstrated that a perpendicular approach is likely to puncture femoral vessels. Vessel puncture can be avoided if an oblique pass is used. Such an approach minimizes the angle between the target nerves and the electrode, and increases the likelihood of the nerve being captured by the lesion made. Multiple lesions need to be made in order to accommodate the variability in location of the articular nerves. CONCLUSIONS: The method that we described has the potential to produce complete and reliable nerve coagulation. Moreover, it minimizes the risk of penetrating the great vessels. The efficacy of this approach should be tested in clinical trials.

Steam pops during irrigated radiofrequency ablation: feasibility of impedance monitoring for prevention

BACKGROUND: Steam pops are a risk of irrigated radiofrequency catheter ablation (RFA) and may cause cardiac perforation. Data to guide radiofrequency (RF) energy titration to avoid steam pops are limited. OBJECTIVE: This study sought to assess the frequency and consequence of audible pops and to determine the feasibility of using the magnitude of impedance change to predict pops. METHODS: We reviewed consecutive endocardial open-irrigated RFA for ventricular tachycardia (VT) with continuously recorded ablation data in 142 patients with structural heart disease. Steam pops were defined as an audible pop associated with a sudden spike in impedance. Ablation lesions before or after pops served as controls. RESULTS: From a total of 4,107 ablation lesions, 62 (1.5%) steam pops occurred in 42 procedures in 38 patients. Perforation with tamponade occurred with 1 of 62 (2%) pops. Applications with pops had a greater impedance decrease (22 +/- 7 Omega vs. 18 +/- 8 Omega, P = .001) and a higher maximum power (45 +/- 5 W vs. 43 +/- 6 W, P = .011), but did not differ in maximum catheter tip temperature (40 degrees C +/- 4 degrees C vs. 40 degrees C +/- 4 degrees C, P = .180) from applications without pops. Eighty percent of pops occurred after impedance decreased by at least 18 Omega. CONCLUSION: During VT ablation with open irrigation, audible pops are infrequent and do not usually cause perforation. Limiting RF power to achieve an impedance decrease of <18 Omega is a feasible method of reducing the likelihood of a pop when perforation risk is of concern.

Statistical analysis of personal radiofrequency electromagnetic field measurements with nondetects

Exposimeters are increasingly applied in bioelectromagnetic research to determine personal radiofrequency electromagnetic field (RF-EMF) exposure. The main advantages of exposimeter measurements are their convenient handling for study participants and the large amount of personal exposure data, which can be obtained for several RF-EMF sources. However, the large proportion of measurements below the detection limit is a challenge for data analysis. With the robust ROS (regression on order statistics) method, summary statistics can be calculated by fitting an assumed distribution to the observed data. We used a preliminary sample of 109 weekly exposimeter measurements from the QUALIFEX study to compare summary statistics computed by robust ROS with a naïve approach, where values below the detection limit were replaced by the value of the detection limit. For the total RF-EMF exposure, differences between the naïve approach and the robust ROS were moderate for the 90th percentile and the arithmetic mean. However, exposure contributions from minor RF-EMF sources were considerably overestimated with the naïve approach. This results in an underestimation of the exposure range in the population, which may bias the evaluation of potential exposure-response associations. We conclude from our analyses that summary statistics of exposimeter data calculated by robust ROS are more reliable and more informative than estimates based on a naïve approach. Nevertheless, estimates of source-specific medians or even lower percentiles depend on the assumed data distribution and should be considered with caution.

Transcatheter closure of patent foramen ovale with radiofrequency: acute and intermediate term results in 144 patients

AIMS: Currently available devices for transcatheter closure of patent foramen ovale (PFO) which rely on a permanent implant have limitations, including late complications. The study objective was to evaluate the safety, feasibility, and effectiveness of the PFx Closure System, the first transcatheter technique for PFO closure without an implantable device. METHODS AND RESULTS: A prospective study of 144 patients was conducted at nine clinical sites from October 2005 through August 2007. All patients had a history of cryptogenic stroke, transient ischemic attack, migraines, or decompression illness. The mean balloon stretched diameter of the PFO was 7.9 +/- 2.5 mm. Technical success (successful application of radiofrequency energy) was achieved in 130 patients. One patient required a transfusion as a result of blood loss during the procedure. There were no other major procedural complications. There were no recurrent strokes, deaths, conduction abnormalities, or perforations following the procedure. At a mean follow-up of 6 months, successful closure was achieved in 79 patients (55%). In PFOs with balloon sized or stretched diameters less than 8 mm, the closure rate was 72% (53/74). CONCLUSION: This study demonstrates that transcatheter closure of a PFO without a permanent implant is technically feasible and safe. Further technique and device modifications are required to achieve higher closure rates.

Ultrasonic acoustic emissions in drought-stressed trees - more than signals from cavitation?

Ultrasonic acoustic emission (UAE) in trees is often related to collapsing water columns in the flow path as a result of tensions that are too strong (cavitation). However, in a decibel (dB) range below that associated with cavitation, a close relationship was found between UAE intensities and stem radius changes. • UAE was continuously recorded on the stems of mature field-grown trees of Scots pine (Pinus sylvestris) and pubescent oak (Quercus pubescens) at a dry inner-Alpine site in Switzerland over two seasons. The averaged 20-Hz records were related to microclimatic conditions in air and soil, sap-flow rates and stem-radius fluctuations de-trended for growth (ΔW). • Within a low-dB range (27 ± 1 dB), UAE regularly increased and decreased in a diurnal rhythm in parallel with ΔW on cloudy days and at night. These low-dB emissions were interrupted by UAE abruptly switching between the low-dB range and a high-dB range (36 ± 1 dB) on clear, sunny days, corresponding to the widely supported interpretation of UAE as sound from cavitations. • It is hypothesized that the low-dB signals in drought-stressed trees are caused by respiration and/or cambial growth as these physiological activities are tissue water-content dependent and have been shown to produce courses of CO2 efflux similar to our courses of ΔW and low-dB UAE.

Feasibility and safety of same-day home discharge after radiofrequency catheter ablation

Interventional cardiology in a day-case setting might reduce logistic constraints on hospital resources. However, in contrast with coronary angioplasty, few data support the feasibility and safety of radiofrequency catheter ablation (RCA). The aim of this prospective, multicenter cohort study was to evaluate the feasibility and safety of RCA in 1,342 patients (814 men; mean age 57 +/- 17 years) considered eligible for ambulatory RCA, according to specific set of criteria, for common atrial flutter (n = 632), atrioventricular nodal reentrant tachycardia (n = 436), accessory pathways (n = 202), and atrial tachycardia (n = 72). Patients suitable for early discharge (4 to 6 hours after uncomplicated RCA) were scheduled for 1-month follow-up. Predictive factors for delayed complications were studied by multivariate analysis. Of the 1,342 enrolled patients, 1,270 (94.6%) were discharged the same day and followed for 1 month; no deaths occurred, and the readmission rate was 0.79% (95% confidence interval 0.30% to 1.27%). Six patients had significant puncture complications, 2 presented with symptomatic delayed pulmonary embolism, and 2 had new onset of poorly tolerated atrial flutter. None of these complications was life threatening. Multivariate analysis did not identify any significant independent predictors for delayed complications. In conclusion, these data suggest that same-day discharge after uncomplicated RCA for routine supraventricular arrhythmias is safe and may be applicable in clinical practice. This approach is known to be associated with significant patient satisfaction and cost savings and can be considered a first-line option in most patients who undergo routine ablation procedures.