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A successful case of maximum voltage-directed cavo-tricuspid isthmus (CTI) ablation using a novel ablation catheter mapping technology in a myotonic dystrophy type I (DM1) patient is reported. The patient complained recurrent episodes of atrial flutter, revealed by the atrio-ventricular electrograms analysis during the routine pacemaker controls. A successful case of maximum voltage-directed cavo-tricuspid isthmus (CTI) ablation using a novel ablation catheter mapping technology in a myotonic dystrophy type I (DM1) patient is reported. The patient complained recurrent episodes of atrial flutter, revealed by the atrio-ventricular electrograms analysis during the routine pacemaker controls.

Background: Sudden cardiac death (SCD) is common in patients with Emery-Dreifuss muscular dystrophy (EDMD) and is attributed to the development of life-threatening arrhythmias that occur in the presence of normal left ventricular systolic function. Heterogeneity of ventricular repolarization is considered to provide an electrophysiological substrate for malignant arrhythmias. QTc dispersion (QTc-D) and JTc dispersion (JTc-D) are electrocardiographic parameters indicative of heterogeneity of ventricular repolarization. The aim of our study was to evaluate the heterogeneity of ventricular repolarization in patients with Emery-Dreifuss muscular dystrophy with preserved systolic and diastolic cardiac function Material/Methods: The study involved 36 EDMD patients (age 20±12, 26 M) and 36 healthy subjects used as controls, matched for age and sex. Heart rate, QRS duration, maximum and minimum QT and JT interval, QTc-D and JTc-D measurements were performed. Results: Compared to the healthy control group, the EDMD group presented increased values of QTc-D (82.7±44.2 vs. 53.1±13.7; P=0,003) and JTc-D (73.6±32.3 vs. 60.4±11.1 ms; P=0.001). No correlation between QTc dispersion and ejection fraction (R=0.2, P=0.3) was found. Conclusions: Our study showed a significant increase of QTc-D and JTc-D in Emery-Dreifuss muscular dystrophy patients with preserved systolic and diastolic cardiac function.

BACKGROUND: Paroxysmal episodes of atrial fibrillation frequently occur in Emery-Dreifuss muscular dystrophy (EDMD). Although previous studies have documented a variety of electrocardiographic abnormalities in EDMD, little is still known about P-wave dispersion (PD), an independent risk factor for the development of atrial fibrillation. The aim of our study was to evaluate the P-wave duration and PD in patients with EDMD with conserved systolic and diastolic cardiac function. METHODS: The study involved 36 patients with EDMD (age, 20 [SD, 12] years; 26 men) and 36 healthy subjects used as controls, matched for age and sex. P-wave dispersion was carefully measured using 12-lead electrocardiogram. Compared with the healthy control group, patients with EDMD presented increased maximum P-wave duration (108.2 [SD, 22.2] vs 97.8 [SD, 11] milliseconds, P = 0.04) and PD (51.4 [SD, 12.8] vs 39.3 [SD, 9.7] milliseconds, P = 0.004) values. No statistically significant differences in left atrium diameter (37.1 [SD, 2.9] vs 34.1 [SD, 4.2] mm, P = 0.3) and maximum left atrium volume (15.2 [SD, 3.8] vs 14.1 [SD, 4.2] mL/m2, P = 0.4) were found between the 2 groups. We divided our study population into 2 subgroups, according to the different genetic diagnosis, patients with laminopathy EDMD (n = 17) or with emerinopathy EDMD (n = 19). No statistically significant differences were found in PD between the 2 subgroups (54.6 [SD, 15.6] vs 50.2 [SD, 11.5] milliseconds, P = 0.4). CONCLUSIONS: Our study showed a significant increase of maximum P-wave duration and PD in patients with EDMD with conserved systolic and diastolic cardiac function.

International audience; Quantum calculations (mainly DFT) and molecular dynamics are increasingly effective tools to evaluate the physico-chemical properties of natural and bio-inspired antioxidants. Thermodynamic parameters (mainly bond dissociation enthalpies (BDE) of the O-H phenolic bond) allowed an accurate prediction of the Free Radical Scavenging Capacity of natural and hemi-synthetic compounds. Based on the Transition State and the Marcus Theories (for atomand electron-transfers, respectively), kinetics was also evaluated providing a better prediction of the antioxidant behaviour in solution or in the organism. Also pro-oxidant effects have been studied including the oxidatively-induced dimerization capacity. In this case, thermodynamic and kinetic calculations explain regio- and stereo-selectivity. MD simulations have been performed to provide an accurate picture of the interaction between natural antioxidants (polyphenols and other π-conjugated derivatives) and lipid bilayer membranes. Molecular dynamics allows evaluation of the ability of these molecules to approach and penetrate the membrane, and to predict their "exact" location and orientation.

Research Note, VITIS - Journal of Grapevine Research, Vol. 54 (2015): Vitis (Special Issue)

Grapevine (Vitis vinifera L.) seeds are rich in polyphenols including proanthocyanidins, molecules with a variety of biological effects including anticancer action. We have previously reported that the grape seed semi-polar extract of Aglianico cultivar (AGS) was able to induce apoptosis and decrease cancer properties in different mesothelioma cell lines. Concomitantly, this extract resulted in enriched oligomeric proanthocyanidins which might be involved in determining the anticancer activity. Through transcriptomic and metabolomic analyses, we investigated in detail the anticancer pathway induced by AGS. Transcriptomics analysis and functional annotation allowed the identification of the relevant causative genes involved in the apoptotic induction following AGS treatment. Subsequent biological validation strengthened the hypothesis that MDM2 could be the molecular target of AGS and that it could act in both a p53-dependent and independent manner. Finally, AGS significantly inhibited tumor progression in a xenograft mouse model of mesothelioma, confirming also in vivo that MDM2 could act as molecular player responsible for the AGS antitumor effect. Our findings indicated that AGS, exerting a pro-apoptotic effect by hindering MDM2 pathway, could represent a novel source of anticancer molecules.

Background A major limitation in the treatment for malignant mesothelioma is related to serious side effects caused by chemotherapeutics and to the development of cancer-resistance. Advances in cancer therapies have been reached thanks to the introduction of alternative approaches, such as the use of phytochemicals. Curcumin-C3complex®/Bioperine® is a commercially standardized extract containing a ratio-defined mixture of three curcuminoids and piperine that greatly increase its bioavailability. Interestingly, the anticancer effect of this formulation has been described in different studies and several clinical trials have been started, but to our knowledge none refers to human mesothelioma. Methods Curcumin-C3complex®/Bioperine® anticancer effect was evaluated in vitro in different human mesothelioma cell lines analysing cell proliferation, colony-forming assay, wound healing assays, invasion assay and FACS analysis. In vivo anticancer properties were analysed in a mesothelioma xenograft mouse model in CD1 Nude mice. Results Curcumin-C3complex®/Bioperine® in vitro induced growth inhibition in all mesothelioma cell lines analysed in a dose- and time-depended manner and reduced self-renewal cell migration and cell invasive ability. Cell death was due to apoptosis. The analysis of the molecular signalling pathway suggested that intrinsic apoptotic pathway is activated by this treatment. This treatment in vivo delayed the growth of the ectopic tumours in a mesothelioma xenograft mouse model. Conclusions Curcumin-C3complex®/Bioperine® treatment strongly reduces in vitro tumorigenic properties of mesothelioma cells by impairing cellular self-renewal ability, proliferative cell rate and cell migration and delays tumor growth in xenograft mouse model by reducing angiogenesis and increasing apoptosis. Considering that curcumin in vivo synergizes drug effects, its administration to treatment regimen may help to enhance drug therapeutic efficacy in mesothelioma. Our results suggest that implementation of standard pharmacological therapies with novel compounds may pave the way to develop alternative approaches to mesothelioma. Electronic supplementary material The online version of this article (10.1186/s13046-019-1368-8) contains supplementary material, which is available to authorized users.

Curcumin, a nontoxic, naturally occurring polyphenol, has been recently proposed for the management of neurodegenerative and neurological diseases. However, a discrepancy exists between the well-documented pharmacological activities that curcumin seems to possess in vivo and its poor aqueous solubility, bioavailability, and pharmacokinetic profiles that should limit any therapeutic effect. Thus, it is possible that curcumin could exert direct regulative effects primarily in the gastrointestinal tract, where high concentrations of curcumin are present after oral administration. Indeed, a new working hypothesis that could explain the neuroprotective role of curcumin despite its limited availability is that curcumin acts indirectly on the central nervous system by influencing the “microbiota−gut−brain axis”, a complex bidirectional system in which the microbiome and its composition represent a factor which preserves and determines brain “health”. Interestingly, curcumin and its metabolites might provide benefit by restoring dysbiosis of gut microbiome. Conversely, curcumin is subject to bacterial enzymatic modifications, forming pharmacologically more active metabolites than curcumin. These mutual interactions allow to keep proper individual physiologic functions and play a key role in neuroprotection.

International audience; Anthocyanins are the main grape pigments. Due to their aromatic cyclic arrangements, they are able to absorb the radiation in the low energy range of the visible spectrum. In the fruit of Vitis vinifera L., the five main anthocyanidins (cyanidin, peonidin, delphinidin, petunidin and malvidin) are present as 3-O-glucosides, as well as their acetyl, p-coumaroyl and caffeoyl ester forms. Despite the huge number of experimental studies dedicated to the anthocyanin profile analysis of grapes and wines, the complete theoretical elucidation of the optical properties of grape anthocyanins is missing. The present work carried out this task through quantum chemistry calculations based on time-dependent density functional theory (TD-DFT), compared to experimental spectra. The differences in visible absorption spectra between the most common grape anthocyanins were rationalized according to B-ring substitution, glucosylation and esterification. A particular attention was given to the intra-molecular copigmentation effect, demonstrating the existence of an intra-molecular charge transfer excited state for the p-coumaroyl and caffeoyl ester forms.

Impact of Continuous Positive Airway Pressure Background Obesity-hypoventilation syndrome (OHS) is defined as daytime hypercapnia and hypoxemia in obese patients with sleep-disordered breathing. We evaluated the electrocardiographic P-wave duration and dispersion (PD) and echocardiographic noninvasive indicators of atrial conduction heterogeneity in OHS patients and the impact of CPAP on atrial conduction and atrial fibrillation incidence. Methods and Results We enrolled 50 OHS patients and 50 sex- and age-matched obese subjects as control. Study population underwent cardiologic evaluation and polysomnography before enrollment, at 1- and 6-month follow-ups after CPAP therapy. The OHS group showed a significant increase in inter-atrial (35.2 ± 8 milliseconds vs. 20.1 ± 2.7 milliseconds, P < 0.0001), intra-left (30.5 ± 7.2 milliseconds vs. 16.5 ± 2 milliseconds, P < 0.0001), and intra-right atrial electromechanical delays (AEMD)(24.8 ± 10 milliseconds vs. 15 ± 2.6 milliseconds, P < 0.0001) as well as in Pmax (130 ± 7.4 milliseconds vs. 97 ± 7.2 milliseconds, P = 0.002) and PD (56.5 ± 8.5 milliseconds vs. 31 ± 7.2 milliseconds, P = 0.002) compared to the control group. Significant improvement was noted after 6 months of CPAP therapy in inter-atrial (35.2 ± 8 milliseconds vs. 24.5 ± 6.3 milliseconds, P < 0.0001), intra-left (30.5 ± 7.2 milliseconds vs. 20.6 ± 5 milliseconds, P = 0.003), and intra-right AEMD (24.8 ± 10 milliseconds vs. 17 ± 7.5 milliseconds, P < 0.0001), as well as in Pmax (130 ± 7.4 milliseconds vs. 95 ± 10 milliseconds, P < 0.0001) and in PD (56.5 ± 8.5 milliseconds vs. 32.5 ± 6 milliseconds, P < 0.0001) in the OHS group. External loop recorder monitoring detected paroxysmal AF in 19 OHS patients (38%) with significant reduction in paroxysmal AF episodes (12 ± 6 vs. 47 ± 12, P < 0.0001) after 6-month CPAP therapy. Conclusion Our findings showed a significant increase of electrocardiographic and echocardiographic indexes of atrial conduction heterogeneity in OHS patients. The CPAP therapy, having a positive impact on atrial conduction time, seems to reduce AF incidence in OHS patients.

Background Paroxysmal supraventricular arrhythmias (SVAs) frequently occur in patients with atrial septal aneurysm (ASA). The aim of the current study was to evaluate the electrocardiographic (P-wave duration and dispersion) and echocardiographic (atrial electromechanical delay, AEMD) noninvasive indicators of atrial conduction heterogeneity in healthy ASA subjects without interatrial shunt and to assess the AEMD role in predicting the SVAs onset in this population. Materials and Methods One hundered ASA patients (41 males, mean age of 32.5 ± 8 years) and 100 healthy subjects used as controls, matched for age and gender, were studied for the occurrence of SVAs during a 4-year follow-up, through 30-day external loop recorder (ELR) monitoring performed every 3 months. ASAs were diagnosed by transthoracic echocardiography based on the criteria of a minimal aneurismal base of ≥15 mm and an excursion of ≥10 mm. Intra-AEMD and inter-AEMD of both atria were measured through tissue Doppler echocardiography. P-wave dispersion (PD) was carefully measured using 12-lead electrocardiogram (ECG). Results Compared to the healthy control group, the ASA group showed a statistically significant increase in inter-AEMD, intra-left AEMD, maximum P-wave duration, and PD. Dividing the ASA group into 2 subgroups (patients with or without SVAs), the inter-AEMD, intra-left AEMD, P max, and PD were significantly higher in the subgroup with SVAs compared to the subgroup without SVAs. There were significant good correlations of intra-left AEMD and inter-AEMD with PD. A cutoff value of 40.1 msec for intra-left AEMD had a sensitivity of 82% and a specificity of 83% in identifying ASA patients at risk for SVA. Conclusion Our results showed that the echocardiographic AEMD indices (intra-left and inter-AEMD) and the PD were significantly increased in healthy ASA subjects without interatrial shunt. PD and AEMD represent noninvasive, inexpensive, useful, and simple parameters to assess the SVAs' risk in ASA patients.

Sudden death is a possible occurrence for newborns younger than 1 year with severe aortic coarctation (CoA) before surgical correction. Basic research and animal experiments have shown electrophysiologic changes during mechanical ventricular pressure overload. The current study aimed to evaluate the effect of severe CoA on the heterogeneity of ventricular repolarization by examining corrected QT and JT interval dispersion (respectively, QTc-D and JTc-D) and electrocardiographic parameters of spatial heterogeneity of ventricular repolarization in newborns with no associated congenital cardiac malformations. The study enrolled 30 isolated severe CoA neonates (age, 45 ± 15 days; 17 males) with normal size and wall thickness of the left ventricle before surgical correction and 30 age- and sex-matched healthy newborns used as control subjects. Heart rate, QRS duration, maximum and minimum QT and JT intervals, and QTc-D and JTc-D measurements were performed. The healthy control group did not significantly differ from the CoA group in terms of heart rate, weight, height, and echocardiographic parameters. Compared with the healthy control group, the CoA group presented significantly increased values of QTc-D (109.7 ± 43.4 vs. 23 ± 15 ms; P = 0.03) and JTc-D (99.1 ± 43.3 vs. 65.8 ± 24.1 ms; P = 0.04). A statistically significant correlation was found between the Doppler peak pressure gradient across the coarctation site and the values of QTc-D (r = 0.48; P = 0.03) and JTc-D (r = 0.42; P = 0.04). Our study showed significantly increased QTc-D and JTc-D in isolated CoA newborns with normal left ventricular geometry. © Springer Science+Business Media, LLC 2011.

Although previous studies have documented a variety of electrocardiogram abnormalities in beta-thalassemia major (β-TM), little is known about P-wave dispersion (PD), an independent risk factor for development of atrial fibrillation. The aim of our study was to evaluate PD in β-TM patients with conserved systolic and diastolic functions. The study involved 40 β-TM patients (age 37.5 ± 10.2; 33 M) and 40 healthy subjects used as controls, matched for age and gender. PD was carefully measured using a 12-lead electrocardiogram. Cardiac iron levels were measured by cardiac magnetic resonance T2 star (CMR T2*) imaging. Comparing to the healthy control group, β-TM group presented increased values of the PD (40.1 ± 12.9 vs. 24 ± 7 ms; P < 0.004) and decreased CMR T2* imaging (29 ± 15 vs. 55 ± 13 ms; P = 0.03). We found a significant correlation between PD and CMR T2* values. Our study showed a significant increase of PD in β-TM patients with conserved systolic and diastolic cardiac functions. Our results indicate that PD is correlated to myocardial iron deposit, as assessed by CMR T2* imaging.