Polymorphous ventricular tachycardia as undesirable effect of the association of quinidine treatment with hysteresis ventricular inhibited pacing

Holter monitoring in a 75-year-old man with a VVI pacemaker with rate hysteresis and concomitant quinidine treatment documented the occurrence of several episodes of non-sustained polymorphous ventricular tachycardia, triggered by each first paced beat following the longer escape interval. These arrhythmias disappeared when quinidine was withdrawn or when the pacemaker was reprogrammed without hysteresis. We hypothesize that the association of the different effects produced by hysteresis and quinidine created the electrophysiologic substrate for the observed arrhythmias.     

Atrial flutter termination by overdrive transesophageal pacing and the facilitating effect of oral propafenone

Transesophageal overdrive atrial pacing is effective and safe for atrial flutter termination. The influence of antiarrhythmic drug therapy on this procedure is controversial. In this study, we investigated whether oral propafenone may facilitate this procedure. Thirty patients with type I atrial flutter were randomized into 2 groups in which transesophageal pacing was attempted: group A, without treatment; and group B, after oral administration of propafenone 600 mg. Transesophageal pacing was effective in interrupting atrial flutter in 53% of patients (8 of 15) in group A and in 87% of patients (13 of 15) in group B. A significant lengthening of the flutter cycle was observed with respect to the baseline in patients given propafenone (261 ± 23 vs 217 ± 25, p < 0.01). Sinus rhythm resumed at a shorter paced cycle in group A patients (166 ± 13 vs 187 ± 14 ms, p < 0.01). The transesophageal threshold for stable atrial capture was significantly lower in group A (20.5 ± 0.2 vs 23.3 ± 1.2, p < 0.01). In no patient was the threshold for atrial capture higher than the pain threshold. We did not observe abrupt enhancement of atrioventricular conduction. We conclude that propafenone is effective and safe when used with transesophageal pacing in the termination of atrial flutter. The slowing effect of the drug on intraatrial conduction and the possible stabilizing effect on the reentry circuit appear to be outweighed by the positive effect of propafenone on the excitable gap of the circuit, facilitating its capture and accounting for the beneficial effect of the drug on arrhythmia termination.     

Activation marker expression and apoptotic susceptibility of T-cell clones derived from CD34(+), young and SENIEUR donors

T-cell clones (TCC) derived from human peripheral blood lymphocytes of a young control, a healthy elderly (SENIEUR) donor, or from CD34(+) hematopoietic progenitor cells were utilised in this study to examine how in vivo and in vitro ageing affects T-cell apoptotic capability. The role of CD25, CD28 and the intracellular proteins, FLICE-inhibitory protein (FLIP), receptor-interacting protein (RIP) and caspase 3 were investigated. We observed an age-related decline in the expression of the IL-2 receptor alpha chain CD25, and absence of the co-stimulatory receptor CD28 on three of the four TCC studied. In young donor- and CD34 cell-derived TCC, but not in SENIEUR donor-derived TCC, we observed an age-related increase in susceptibility of the cells to mFas-L-induced apoptosis, which correlated with the age-related decrease of CD25 expression. Expression levels of full-length RIP and FLIP did not show any correlation to apoptotic susceptibility. However, expression levels of the cleaved form of RIP were greatly reduced in the SENIEUR donor-derived TCC, which together with a trend towards increased caspase 3 activity, could indicate an age-related alteration in utilisation of different apoptotic signalling pathways.     

Mobility and satisfaction with a microprocessor-controlled knee in moderately active amputees: A multi-centric randomized crossover trial

Objective

Microprocessor-controlled knees are generally prescribed and reimbursed for active amputees. Recent studies suggested that this technology could be useful for amputees with moderate activity level. We compared the efficiency of a microprocessor-controlled knee (MPK, Kenevo, Otto Bock) and non-MPKs (NMPKs) in these indications.

Assessment of Remote Myocardium Heterogeneity in Patients with Ventricular Tachycardia Using Texture Analysis of Late Iodine Enhancement (LIE) Cardiac Computed Tomography (cCT) Images

Purpose

Diffuse remodeling of myocardial extra-cellular matrix is largely responsible for left ventricle (LV) dysfunction and arrhythmias. Our hypothesis is that the texture analysis of late iodine enhancement (LIE) cardiac computed tomography (cCT) images may improve characterization of the diffuse extra-cellular matrix changes. Our aim was to extract volumetric extracellular volume (ECV) and LIE texture features of non-scarred (remote) myocardium from cCT of patients with recurrent ventricular tachycardia (rVT), and to compare these radiomic features with LV-function, LV-remodeling, and underlying cardiac disease.

Procedures

Forty-eight patients suffering from rVT were prospectively enrolled: 5/48 with idiopathic VT (IVT), 23/48 with post-ischemic dilated cardiomyopathy (ICM), 9/48 with idiopathic dilated cardiomyopathy (IDCM), and 11/48 with scars from a previous healed myocarditis (MYO). All patients underwent echocardiography to assess LV systolic and diastolic function and cCT with pre-contrast, angiographic, and LIE scan to obtain end-diastolic volume (EDV), ECV, and first-order texture parameters of Hounsfield Unit (HU) of remote myocardium in LIE [energy, entropy, HU-mean, HU-median, standard deviation (SD), and mean absolute deviation (MAD)].

Results

Energy, HU mean, and HU median by cCT texture analysis correlated with ECV (rho?=?0.5650, rho?=?0.5741, rho?=?0.5068; p?<?0.0005). cCT-derived ECV, HU-mean, HU-median, SD, and MAD correlated directly to EDV by cCT and inversely to ejection fraction by echocardiography (p?<?0.05). SD and MAD correlated with diastolic function by echocardiography (rho?=?0.3837, p?=?0.0071; rho?=?0.3330, p?=?0.0208). MYO and IVT patients were characterized by significantly lower values of SD and MAD when compared with ICM and IDCM patients, independently of LV-volume systolic and diastolic function.

Conclusions

Texture analysis of LIE may expand cCT capability of myocardial characterization. Myocardial heterogeneity (SD and MAD) was associated with LV dilatation, systolic and diastolic function, and is able to potentially identify the different patterns of structural remodeling characterizing patients with rVT of different etiology.

     

Maltese Mushroom (Cynomorium coccineum L.) as Source of Oil with Potential Anticancer Activity

The present study aimed to examine the potential anticancer properties of fixed oil obtained from Maltese mushroom (Cynomorium coccineum L.), an edible, non-photosynthetic plant, used in traditional medicine of Mediterranean countries to treat various ailments and as an emergency food during the famine. We investigated the effect of the oil, obtained from dried stems by supercritical fractioned extraction with CO₂, on B16F10 melanoma and colon cancer Caco-2 cell viability and lipid profile. The oil, rich in essential fatty acids (18:3n-3 and 18:2n-6), showed a significant growth inhibitory effect on melanoma and colon cancer cells. The incubation (24 h) with non-toxic oil concentrations (25 and 50 μg/mL) induced in both cancer cell lines a significant accumulation of the fatty acids 18:3n-3 and 18:2n-6 and an increase of the cellular levels of eicosapentaenoic acid (20:5n-3) with anticancer activity. Moreover, the oil exhibited the ability to potentiate the growth inhibitory effect of the antitumor drug 5-fluorouracil in Caco-2 cells and to influence the melanin content in B16F10 cells. The results qualify C. coccineum as a resource of oil, with potential benefits in cancer prevention, for nutraceutical and pharmaceutical applications.     

Model-based prediction of the acute and long-term safety profile of naproxen in rats

Background and Purpose

Despite the increasing importance of biomarkers as predictors of drug effects, toxicology protocols continue to rely on the experimental evidence of adverse events (AEs) as a basis for establishing the link between indicators of safety and drug exposure. Furthermore, biomarkers may facilitate the translation of findings from animals to humans. Combined with a model-based approach, biomarker data have the potential to predict long-term effects arising from prolonged drug exposure. Here, we used naproxen as a paradigm to explore the feasibility of a biomarker-guided approach for the prediction of long-term AEs in humans.

Experimental Approach

An experimental toxicology protocol was set up for evaluating the effects of naproxen in rats, in which four active doses were tested (7.5, 15, 40 and 80 mg·kg⁻¹). In addition to AE monitoring and histology, a few blood samples were also collected for the assessment of drug exposure, TXB₂ and PGE₂ levels. Non-linear mixed effects modelling was used to analyse the data and identify covariate factors on the incidence and severity of AEs.

Key Results

Modelling results showed that besides drug exposure, maximum PGE₂ inhibition and treatment duration were also predictors of gastrointestinal ulceration. Although PGE₂ levels were clearly linked to the incidence rates, it appeared that ulceration severity is better predicted by measures of drug exposure.

Conclusions and Implications

These results show that the use of a model-based approach provides the opportunity to integrate pharmacokinetics, pharmacodynamics and toxicity data, enabling optimization of the design, analysis and interpretation of toxicology experiments.     

Water wettability of graphene: interplay between the interfacial water structure and the electronic structure

Wetting phenomena are ubiquitous and impact a wide range of applications. Simulations so far have largely relied on classical potentials. Here, we report the development of an approach that combines density-functional theory (DFT)-based calculations with classical wetting theory that allows practical but sufficiently accurate determination of the water contact angle (WCA). As a benchmark, we apply the approach to the graphene and graphite surfaces that recently received considerable attention. The results agree with and elucidate the experimental data. For metal-supported graphene where electronic interactions play a major role, we demonstrate that doping of graphene by the metal substrate significantly alters the wettability. In addition to theory, we report new experimental measurements of the WCA and the force of adhesion that corroborate the theoretical results. We demonstrate a correlation between the force of adhesion and WCA, and the use of the atomic force microscope (AFM) technique as an alternative measure for wettability at the nanoscale. The present work not only provides a detailed understanding of the wettability of graphene, including the role of electrons, but also sets the stage for studying the wettability alteration mechanism when sufficiently accurate force fields may not be available.

Wettability of graphene is characterized from first principles.

Wetting phenomena are ubiquitous in a variety of practical issues, including adhesion,¹ friction,² interfacial thermal conductance (Kapitza conductance),^3,4 to name just a few. Graphene has emerged as an important material for applications where water wettability plays a major role, e.g., as a lubricant,⁵ small-molecule gas sensor,^6,7 desalination membrane,^8,9 protective coating from electrochemical degradation,¹⁰ promotive coating for dropwise condensation,¹¹etc. Among these applications, to wet or not to wet is the key problem.^12,13 More recently, doping-induced tunable wettability was reported for graphene.^14,15Interactions between the wetting liquid and the solid it rests on are responsible for the wetting properties of a surface. The binding energy of individual molecules on the solid surface, obtained by quantum-mechanical calculations, has at times been used as an indicator of wettability.^14,16 A better indicator, however, is the water contact angle (WCA), an experimentally easily accessible parameter that characterizes macroscopically a surface''s wettability by water.^17,18 Large WCA, >90°, signifies hydrophobic behavior, whereas small WCA, <90°, signifies hydrophilic behavior. The past few years have witnessed increasing efforts to understand the wetting mechanism of graphitic carbon surfaces. Theoretical calculations of WCAs of graphitic carbon surfaces have so far been done primarily using classical potentials, by constructing an analytical interaction potential between water and the solid surface based on interatomic Lennard-Jones potentials^19–21 or classical molecular dynamics (CMD) simulations.^19,22–29 In those pioneering studies with the work-of-adhesion approach, one first computes the work of adhesion of a water slab on a surface and then employs the Young-Dupré equation that relates the work of adhesion to the WCA.^19,25–28 Alternatively, CMD can be sued to measures the shape of a water droplet on a surface and extract the WCA.^22–24Though these approaches have provided significant insights into wetting behavior,^19,22–28 they depend on the availability of reliable classical potentials. The construction of such potentials becomes a difficult task when many atomic species are present. For example, the interplay between ions such as Ca²⁺, Mg²⁺, SO₄²⁻, Na⁺ and Cl⁻ in saline water and calcite (CaCO₃) surfaces is responsible for the wettability alteration for oil recovery.^30,31 There are also cases, e.g., monolayers on metallic substrates, where explicit electron doping effects may play a major role, requiring electronic-structure calculations. While density functional theory (DFT) is the method of choice for predictive, atomic-scale calculations of interactions at the solid–water interface, the major difficulty lies in the limited time and length scales achievable by quantum MD (QMD) simulations.³² So far there exists only one report of QMD simulations of water nanodroplets, on graphene and hexagonal boron nitride monolayers.³³In this paper, we adopt the method based on the work of adhesion and the Young-Dupré equation, and employ an approximation that allows practical but sufficiently accurate DFT-based determination of the WCA. Benchmark calculations confirm that graphitic carbon surfaces are nonpolar and intrinsically hydrophilic, with their wettability determined by the dispersive interaction. The WCA gradually decreases with increasing number of graphene layers N, while a monolayer of adsorbed hydrocarbons is sufficient to render graphene hydrophobic, complementing similar results obtained using classical potentials.^20,21,25,34 In the presence of a metal substrate, electronic structure comes into play and electron doping of the graphene sheet by the metal substrate alters the wettability of graphene. We report new WCA and AFM (atomic force microscopy) measurements for Cu-supported monolayer and multilayer graphene that further corroborate the theoretical results. Finally, we demonstrate a correlation between the force of adhesion and WCA, and the use of the AFM technique as an alternative measure for wettability at the nanoscopic scale.