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A set of nitro-activated ruthenium-based Hoveyda-Grubbs type olefin metathesis catalysts bearing sterically modified N -hetero-cyclic carbene (NHC) ligands have been obtained, characterised and studied in a set of model metathesis reactions. It was found that catalysts bearing standard SIMes and SIPr ligands ( 4a and 4b ) gave the best results in metathesis of substrates with more accessible C-C double bonds. At the same time, catalysts bearing engineered naphthyl-substituted NHC ligands ( 4d - e ) exhibited high activity towards formation of tetrasubstituted C-C double bonds, the reaction which was traditionally Achilles' heel of the nitro-activated Hoveyda-Grubbs catalyst.

Background: COPD represents a major global health issue, which is often accompanied by cardiovascular diseases. A considerable body of evidence suggests that cardiovascular risk is elevated by the activation of blood platelets, which in turn is exacerbated by inflammation. As reactive oxygen species are believed to be an important factor in platelet metabolism and functioning, the aim of our study was to perform a complex assessment of mitochondrial function in platelets in chronic smoke exposed animals with COPD-like lung lesions., Materials and Methods: Eight-week-old, male Dunkin Hartley guinea pigs (the study group) were exposed to the cigarette smoke from commercial unfiltered cigarettes (0.9 mg/cig of nicotine content) or to the air without cigarette smoke (control group), using the Candela Constructions ® exposure system. The animals were exposed for 4 hours daily, 5 days a week, with 2×70 mL puff/minute, until signs of dyspnea were observed. The animals were bled, and isolated platelets were used to monitor blood platelet respiration. The mitochondrial respiratory parameters of the platelets were monitored in vitro based on continuous recording of oxygen consumption by high-resolution respirometry., Results: An elevated respiration trend was observed in the LEAK-state (adjusted for number of platelets) in the smoke-exposed animals: 6.75 (5.09) vs 2.53 (1.28) (pmol O 2 /[s ⋅ 110 8 platelets]); bootstrap-boosted P 1α =0.04. The study group also demonstrated lowered respiration in the ET-state (normalized for protein content): 12.31 (4.84) vs 16.48 (1.72) (pmol O 2 /[s ⋅ mg of protein]); bootstrap-boosted P 1α =0.049., Conclusion: Our results suggest increased proton and electron leak and decreased electron transfer system capacity in platelets from chronic smoke-exposed animals. These observations may also indicate that platelets play an important role in the pathobiology of COPD and its comorbidities and may serve as a background for possible therapeutic targeting. However, these preliminary outcomes should be further validated in studies based on larger samples., Competing Interests: Disclosure The costs of this study were defrayed from regular finances of the Department of Pneumology and Allergy, The animal house of the Pharmaceutical Faculty, Department of Hemostasis and Hemostatic Disorders, of Medical University of Lodz, Poland, and of the Department of General and Inorganic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec of Medical University of Silesia, and Institute of Occupational Medicine and Environmental Health in Sosnowiec. AB is also supported by the fund for the young investigators of the Medical University of Lodz (502-03/1-151-03/502-14-364-18). KS received the Etiuda scholarship funded by the NCN (2016/20/T/NZ3/00505). LK is supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number P50DA036105 and the Center for Tobacco Products of the U.S. Food and Drug Administration. The content is solely the responsibility of the authors and does not necessarily represent the views of the NIH or the FDA. LK works as an expert for the Polish National Committee for Standardization and for the European Committee for standardization of requirements and test methods for e-liquids and emissions. Additionally, JK is and LK was an employee of the Institute of Occupational Medicine and Environmental Health. One of the institute’s objectives is outsourcing for the industrial sector, including manufacturers of e-cigarettes. However, this has no influence on studies design. The other authors report no conflicts of interest in this work.

The circularly polarized luminescence (CPL) spectrum of thioflavin T (ThT) bound to insulin amyloid fibrils has been measured for the first time. It has been found that the samples exhibiting induced circular dichroism (CD) retain the optical activity in the CPL spectra, with the same sign of the rotatory strength. The fluorescence dissymmetry factor is substantial (of the order of magnitude 10(-2) ). Unlike in the corresponding CD and absorption spectra, there is no shift of the CPL band with respect to the fluorescence band. It has been verified that the measured CPL spectra are free from artifacts from circularly polarized scattering of emitted light by conducting additional measurements in a medium with a refractive index similar to insulin (methylsalicylate). The CD and CPL spectra have been interpreted by means of density functional calculations carried out for ThT in its ground and first excited states in different dielectric environments and for ThT interacting with an aromatic ring. It has been found that the presence of an aromatic ring close to the ThT molecule induces Cotton effects of the same order of magnitude as the stabilization of one enantiomeric conformer. Thus, it is expected that both mechanisms contribute to the induced CD and CPL effect to a similar degree., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Unlabelled: Despite common use of reperfusion therapy, particularly primary PCI during acute myocardial infarction, steadily increasing number of patients with low left ventricular ejection fraction, with heart failure (HF), requiring frequent rehospitalisation justifies the study establishing the best indices of prediction of major adverse cardiac events (MACE) occurrence. The aim of the study was to define the frequency of MACE (death, re MI, sVT, rehospitalisation for HF) in patients with acute anterior wall myocardial infarction in 6 month follow up and the factors determinatig its occurence. The 115 consecutive patients (86 males of age 57.7 +/- 11 yrs) with first anterior MI were studied. After successful PCI (TIMI 3) the angiographic assessment was performed (MBG 0-1 - no perfusion, MBG 2-3 - perfusion preserved). During first 48 hours 12-lead ECG was monitored in order to analyse the time to reduction of ST elevation in the lead with the highest elevation (deltatST 50%). On 2nd day LV function (LVEF and WMSI) and dyssfunctional segment perfusion (RPSI) were assessed. On 5th day Holter monitoring with arrhythmia and time domain parameters (SDNN, rMSSD) of heart rate variability were performed, on 30 day TWA test was done., Results: During 180 follow-up 18 MACE occurred (3 death, 2 MI, 11 rehospitalisations for HF). In univariate analysis cigarette smoking, higher maximum troponin I value, LVEDV, LVESV, ST elevation sum, longer time to reduction of ST elevation, lower LVEF and RPSI, lack of microvessel integrity and positive TWA test had significant relationship with occurrence of MACE. The multivariate analysis of Cox proportional risk regression demonstrated that only lower value of RPSI and LVEF, longer time of ST elevation reduction in the lead with the highest ST elevation and positive TWA test were independent indices of MACE prediction., Conclusions: Cumulative evaluation of LVEF, indices of preserved perfusion and results of TWA test turned out to be the best predictors of MACE occurrence in 6 month follow up in patients after anterior MI treated with PCI.