Antioxidant activity of β-carboline derivatives

The investigated β-carboline derivatives were synthesized to elucidate their activity as 5-HT1A and 5- HT2A receptor ligands. Compounds containing a carboline ring system belong to a large family of biological active indoles, which are very important for the function of the central nervous system (1). The research was carried out to determine antioxidative or oxidative properties of these derivatives. Analysis of antioxidative capacity as indication of oxidative stress was based on ability to scavenge free radicals by DPPH (free radical scavenging activity test) and FRAP test (2, 3). The results were compared to those of standard substances like vitamin C, trolox, quercetin and curcumin. The research of derivatives of β-carboline shows antioxidative activity comparable to vitamin C. Compounds 1, 5 and 6, but only in low concentration, have antioxidative activity. Substance 10 was classified as that with prooxidative activity

Diastolic dyssynchrony and its exercise-induced changes affect exercise capacity in patients with heart failure with reduced ejection fraction

Background: Left ventricular (LV) diastolic dyssynchrony is common in patients with heart failure with reduced ejection fraction (HFREF). Little is known however, about its pathophysiology and clinical effects. Herein is hypothesized that presence of diastolic dyssynchrony at rest or at exercise may importantly contribute to HF symptoms. The aim was to investigate the influence of diastolic dyssynchrony and its exercise-induced changes on exercise capacity in HFREF patients. Methods: Patients with stable, chronic HF, LV ejection fraction < 35%, sinus rhythm and QRS ≥ 120ms were eligible for the study. Rest and cyclo-ergometer exercise echocardiography were performed. Diastolic dyssynchrony was defined as opposing-wall-diastolic-delay ≥ 55 ms measured in tissue-Doppler imaging. Exercise capacity was assessed by peak oxygen consumption (VO2peak). Association between diastolic dyssynchrony and VO2peak was assessed in univariate regression analysis and further adjusted for possible confounders. Results: 48 patients were included (aged 63.7 ± 12.2). Twenty-seven (56.25%) had diastolic dyssynchrony at rest and 13 (27%) at exercise. Twenty-two (46%) experienced a change in diastolic dyssynchrony status during exercise. In univariate models diastolic dyssynchrony at rest or at exercise were associated with lower VO2peak (beta coefficient = –3.8, p = 0.004; beta coefficient = –3.6, p = 0.02, respectively). However, the ability to restore diastolic synchronicity during exercise was associated with higher VO2peak (beta coefficient = 3.4, p = 0.04) and remained an important predictor of exercise capacity after adjustment for age and HF etiology. Conclusions: The ability to restore diastolic synchronicity at exercise predicts exercise capacity in patients with HFREF

Ischaemic aetiology predicts exercise dyssynchrony in patients with heart failure with reduced ejection fraction

Background: Left ventricular (LV) dyssynchrony is common in patients with heart failure with reduced ejection fraction (HFREF). However, various conditions including exercise may alter its presence. LV dyssynchrony at exercise (ExDYS) has been associated with lower cardiac performance and exercise capacity but with higher cardiac resynchronization therapy (CRT) response. Therefore, understanding mechanisms underlying ExDYS may improve patient selection for CRT. Aims: To investigate for predictors of ExDYS among patients with HFREF and prolonged QRS duration. Methods: Consecutive patients with stable, chronic HF, LVEF<35%, sinus rhythm and QRS≥120ms were eligible. 2D echocardiography and tissue-Doppler were performed at rest and peak cyclo-ergometer exercise to assess LV systolic (LVEF) and diastolic function [mitral E-to-e’-wave velocities (E/e’)] and dyssynchrony. Dyssynchrony was defined as a maximal difference between time-to-peak systolic velocities of≥65ms from opposing basal segments. Results: We included 48 patients (aged 63.7±12.2, 81.3% male). Ischaemic aetiology (ICM) was present in 23 (47.9%). Dyssynchrony at rest (rDYS) was present in 32 (66.6%) patients, while ExDYS in 23 (47.9%). ExDYS correlated with ICM, lower LVEF and higher E/e’ ratio. ICM remained significant predictor of ExDYS in multiple regression model (OR:4.3, 95%CI:1.2–15.7, p=003). On exercise, 19 (39.5%) patients changed the rDYS status. While, exercise-induced dyssynchronization was observed only in ICM patients, exercise-induced resynchronization was more likely in patients with lower rest E/e’ ratio (OR:0.85, 95%CI:0.75–0.97, p=0.02). Conclusions: Ischaemic aetiology of HFREF is an important predictor of ExDYS. Restoration of LV synchronicity during exercise is more likely in patients with less advanced LV diastolic dysfunction

Virtual histology to evaluate mechanisms of pulmonary artery lumen enlargement in response to balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) results from an obstruction of pulmonary arteries (PAs) by organized thrombi. The stenosed PAs are targeted during balloon pulmonary angioplasty (BPA). We aimed to evaluate the mechanism of BPA in inoperable patients with CTEPH. We analyzed stenosed PAs with intravascular grey-scale ultrasound (IVUS) to determine the cross-sectional area (CSA) of arterial lumen and of organized thrombi. The composition of organized thrombi was assessed using virtual histology. We distinguished two mechanisms of BPA: Type A with dominant vessel stretching, and type B with dominant thrombus compression. PAs were assessed before (n = 159) and after (n = 98) BPA in 20 consecutive patients. Organized thrombi were composed of dark-green (57.1 (48.0–64.0)%), light-green (34.0 (21.4–46.4)%), red (6.4 (2.9–11.7)%;) and white (0.2 (0.0–0.9)%) components. The mechanism type depended on vessel diameter (OR = 1.09(1.01–1.17); p = 0.03). In type B mechanism, decrease in the amount of light-green component positively correlated with an increase in lumen area after BPA (r = 0.50; p = 0.001). The mechanism of BPA depends on the diameter of the vessel. Dilation of more proximal PAs depends mainly on stretching of the vessel wall while dilation of smaller PAs depends on compression of the organized thrombi. The composition of the organized thrombi contributes to the effect of BPA

Epitaxial hexagonal boron nitride for hydrogen generation by radiolysis of interfacial water

Hydrogen is an important building block in global strategies towards a future green energy system. To make this transition possible, intense scientific efforts are needed, also in the field of materials science. Two-dimensional crystals, such as hexagonal boron nitride (hBN), are very promising in this regard, as it was demonstrated that micrometer-sized exfoliated flakes are excellent barriers to molecular hydrogen. However, it remains an open question whether large-area layers fabricated by industrially relevant methods preserve such promising properties. In this work we show that electron beam-induced splitting of water creates hBN bubbles that effectively store molecular hydrogen for weeks and under extreme mechanical deformation. We demonstrate that epitaxial hBN allows direct visualization and monitoring of the process of hydrogen generation by radiolysis of interfacial water. Our findings show that hBN is not only a potential candidate for hydrogen storage, but also holds promise for the development of unconventional hydrogen production schemes