Theoretical Study on HF Elimination and Aromatization Mechanisms: A Case of Pyridoxal 5′ Phosphate-Dependent Enzyme

Pyridoxal 5-phosphate (PLP), the phosphorylated and the oxidized form of vitamin B6 is an organic cofactor. PLP forms a Schiff base with the ϵ-amino group of a lysine residue of PLP-dependent enzymes. γ-Aminobutyric acid (GABA) aminotransferase is a PLP-dependent enzyme that degrades GABA to succinic semialdehyde, while reduction of GABA concentration in the brain causes convolution besides several neurological diseases. The fluorine-containing substrate analogues for the inactivation of the GABA-AT are synthesized extensively in cases where the inactivation mechanisms involve HF elimination. Although two proposed mechanisms are present for the HF elimination, the details of the base-induced HF elimination are not well identified. In this density functional theory (DFT) study, fluorine-containing substrate analogue, 5-amino-2-fluorocyclohex-3-enecarboxylic acid, is particularly chosen in order to explain the details of the HF elimination reactions. On the other hand, the experimental studies revealed that aromatization competes with Michael addition mechanism in the presence of 5-amino-2-fluorocyclohex-3-enecarboxylic acid. The results allowed us to draw a conclusion for the nature of HF elimination, besides the elucidation of the mechanism preference for the inactivation mechanism. Furthermore, the solvent phase calculations carried out in this study ensure that the proton transfer steps should be assisted either by a water molecule or a base for lower activation energy barriers

Immediate electrical storm of Torsades de Pointes after CRT-D implantation in an ischemic cardiomyopathy patient

Cardiac resynchronization therapy with an implantable cardioverter-defibrillator (CRT-D) is the preferred treatment for patients with severe heart failure, dyssynchrony, and an increased risk of sudden cardiac death or for primary ventricular arrhythmia survivors. Rarely, left ventricular epicardial pacing can induce ventricular tachyarrhythmia rather than a beneficial effect. We describe an ischemic cardiomyopathy patient who underwent CRT-D therapy and developed sustained torsades de pointes (TdP) immediately after switching to biventricular pacing (BVP) mode. Here, TdP possibly developed owing to the change in the dispersion of repolarization of the left ventricle myocardium. The diagnosis and management of BVP-induced ventricular arrhythmia is discussed

Prevalence of metabolic syndrome in young patients with ST-elevation myocardial infarction

Background: Atherosclerotic cardiovascular disease influences young patients as well as the elderly. A large proportion of patients with coronary artery disease (CAD) have metabolic syndrome (MS), although the frequency and association of its different components are not clear. To the best of our knowledge, there is no any study about the prevalence of MS among young patients with ST-elevation myocardial infarction (STEMI). We sought to determine the prevalence of MS in patients below 46 years of age who presented with STEMI and underwent primary percutaneous coronary intervention. Methods: In the present prospective study, 141 consecutive patients with STEMI <46 years of age admitted to intensive coronary care unit. STEMI was defined according to the ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. All patients were grouped presence of MS. In the second step, the components of MS were analyzed, excluding patients with diabetes mellitus (DM). Results: The total prevalence of MS was 46.8% (n = 66). In MS group, the most frequent component of MS was low high-density lipoprotein (HDL) levels (84.8%), followed by elevated triglycerides (TGs) (78.1%). A total of 121 patients did not have DM and 51 (42.1%) of these patients presented with MS. Conclusions: The prevalence of MS in young patients with STEMI is high. Low HDL cholesterol (HDLc) concentrations and high TG levels are cardiovascular risk factors, regardless of low-density lipoprotein cholesterol levels and they are found too often in our study. These results highlight the need to implement preventative strategies for reducing overall cardiovascular risk in young patients as well as elderly

Effects of RAAS blocker use on AKI in elderly hypertensive STEMI patients with propensity score weighed method

Studies reported conflicting results on the effect of renin-angiotensin-aldosterone system (RAAS) blocker use on acute kidney injury (AKI) in patients undergoing elective coronary angiography but association in elderly patients with ST-elevation myocardial infarction (STEMI) is not known. Also, there are limited data on the effect of inflammatory markers on AKI. We aimed to investigate the effects of RAAS blocker pretreatment and inflammatory markers on AKI in this population. A total of 471 patients were compared according to presence of RAAS blocker pretreatment at admission. Conventional and inverse probability weighed conditional logistic regression were used to determine independent predictors of AKI. Mean age of the study group was 75.4 ± 7.1 years and 29.1% of the patients were female. AKI was observed in 17.2% of the study population. Weighted conditional multivariable logistic regression analysis revealed that AKI was associated with baseline creatinine levels and C-reactive protein/albumin ratio (CAR) (OR 2.08, 95% CI = 1.13–3.82, p = .02 and OR 1.19, 95% CI = 1.01–1.41, p = .04, respectively). No significant association was found between RAAS blocker pretreatment and AKI. CAR and elevated baseline creatinine levels were independent predictors of AKI in this patient group

A Theoretical Study On Rh(I) Catalyzed Enantioselective Conjugate Addition Reactions of Fluoroalkylated Olefins

In this study, quantum mechanical calculations have been performed to elucidate the mechanism and enantioselectivity in rhodium-catalyzed 1,4-conjugate addition reaction of a series of aryl groups to electron-deficient 4,4,4-trifluoro-1-phenyl-2-buten-1-one in the presence of (<i>S</i>)-BINAP. Conjugate addition of unsubstituted, <i>o</i>-CH₃, <i>p</i>- and <i>o</i>-Cl substituted phenyl groups were considered to explain steric and electronic effects on the reaction mechanism. The activation energy difference between benzene and <i>o</i>-toluene-substituted systems (8.1 kcal/mol for the <i>R</i> isomer) has shown the impact of steric effects of substituents at the ortho position. The electronic effect of a Cl substituent at the ortho position was demonstrated by an even higher energy barrier (11.9 kcal/mol of energy difference between benzene and <i>o</i>-Cl for R enantiomer). The experimental unreactivity of the <i>o</i>-Cl-substituted system was also confirmed with the calculated high activation energies for both <i>R</i> and <i>S</i> (29.9 and 31.7 kcal/mol for <i>R</i> and <i>S</i>, respectively) product formations. The system with para-positioned Cl revealed almost the same barriers for benzene, indicating that substituents at the para position do not have significant electronic or steric effects in this reaction. In all the modeled sets, experimental <i>R</i> product predominance could be reproduced. The quantitative trend was satisfied with the B3LYP/6-31G* functional, where the LANL2DZ effective core potential was used for Rh, P, S, and Cl atoms. Benchmark calculations have been performed to validate the level of theory in this study

Prognostic impact of cardiohepatic syndrome in patients with ST-segment elevation myocardial infarction - Supplementary Figure

Background: Cardiohepatic syndrome (CHS) indicates a bidirectional interaction between the heart and liver. This study was designed to evaluate the impact of CHS on in-hospital and long-term mortality in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention. Materials & methods: 1541 consecutive STEMI patients were examined. CHS was defined as the elevation of at least two of three cholestatic liver enzymes: total bilirubin, alkaline phosphatase and gamma-glutamyl transferase. Results: CHS was present in 144 (9.34%) patients. Multivariate analyses revealed CHS as an independent predictor of in-hospital (odds ratio: 2.48; 95% CI: 1.42–4.34; p = 0.001) and long-term mortality (hazard ratio: 2.4; 95% CI: 1.79–3.22; p The presence of CHS is a predictor of poor prognosis in patients with STEMI and should be evaluated during the risk stratification of these patients.</p

Role of the <i>n</i>+1 amino acid residue on the deamidation of asparagine in pentapeptides

<div><p>Deamidation plays an important role in biochemical phenomena such as aging. The role of the <i>n</i> + 1 residue on the deamidation of asparagine (asparagine being the <i>n</i>th residue) in three pentapeptide chains (GGNGG, GGNMG and GGNIG) has been analysed with hybrid computational tools. Potentials of mean force at 300 K were calculated from the MD/replica exchange simulations using weighted histogram analysis (WHAM) in explicit water. The snapshots were clustered taking into account the requirements of the plausible deamidation mechanisms, as such the tautomerisation of the asparagine side chain as initial step has been confirmed, based on the proximity of water to the deamidation site. The ultimate goal being to gain an insight on the peptide backbone N-H acidity, quantum mechanical calculations have been carried out. For this purpose, the distribution of Φ/Ψ, Φ₂/Ψ and end-to-end distances  deduced from the WHAM diagrams have been considered and a total of 110 structures have been sampled. These neutral pentapeptides as well as their corresponding anions have been optimised (B3LYP/6-31++G(d,p)) in implicit water in order to gain an insight on the peptide backbone N-H acidity. In this study, we have shown that the open conformations of the neutrals and the anions, which display a β sheet like structure are well populated and their <i>pK_a</i>s rank in the same order as the deamidating half-lives, that is the peptides that deaminate fastest can more readily access conformations that are more acidic.</p></div

Normal echocardiographic measurements in a Turkish population: The Healthy Heart ECHO-TR Trial.

Objective: Normal reference values for the cardiac chambers are widely based on cohorts from European or American populations. In this study, we aimed to obtain normal echocardiographic measurements of healthy Turkish volunteers to reveal the age, gender, and geographical region dependent differences between Turkish populations and other populations