The association between coronary flow rate and impaired heart rate recovery in patients with metabolic syndrome: A preliminary report

Background: The aim of this study is to evaluate heart rate recovery (HRR) and association between coronary flow rate and HRR in patients with metabolic syndrome (MS) who had morphologically normal coronary angiogram.Methods: Study population included 43 patients with MS and 37 control subjects without MS. All patients were selected from individuals who had recently undergone coronary angiography in our hospital and were diagnosed as having angiographically normal coronary arteries. Exercise stress test results obtained prior to coronary angiography were evaluated for calculating HRR and other parameters. In addition, coronary flow was objectively evaluated for each major coronary artery in each subject using TIMI frame count method.Results: All HRR values calculated were detected significantly lower in MS group compared to controls (HRR first: 32 ± 9 vs. 37 ± 10; p = 0.01, second: 46 ± 11 vs. 52 ± 11; p = 0.03, third: 51 ± 12 vs. 59 ± 12; p = 0.00, fourth: 54 ± 13 vs. 61 ± 2; p = 0.02). TIMI frame counts for each major epicardial coronary artery and mean TIMI frame count were also found to be significantly higher in MS group compared to controls (left anterior descending artery:51 ± 24 vs. 39 ± 15; p = 0.009, left circumflex artery: 32 ± 11 vs. 24 ± 7; p = 0.001, right coronary artery: 33 ± 14 vs. 24 ± 10; p = 0.003, mean TIMI frame count: 38 ± 15 vs. 29 ± 9;p = 0.002). Additionally, significant negative correlations were also detected between HRR first minute and coronary TIMI frame count values in patients with MS. None of MS parameters did not affect HRR values, however mean TIMI frame count independently associated with HRR first minute (p = 0.04) in patients with MS.Conclusions: Impaired coronary blood flow occurring in MS might be a clue of autonomic dysfunction in addition to previously known endothelial dysfunction.

Evaluating functional capacity, and mortality effects in the presence of atrial electromechanical conduction delay in patients with systolic heart failure

Objective: Atrial functions are relatively suppressed in heart failure (HF). We aimed to investigate the associations of intra- and inter-atrial electromechanical conduction delay (EMCD) with functional class and mortality over a 12-month follow-up period. Methods: The prospective study included 65 patients with systolic HF and 65 healthy subjects with normal sinus rhythm. Left ventricular (LV) systolic functions and left atrial (LA) dimensions and volumes were evaluated by transthoracic echocardiography. Tissue Doppler imaging (TDI) signals at the lateral border of the mitral annulus (lateral PA’), septal mitral annulus (septal PA’), and tricuspid annulus (tricuspid PA’) were measured. Intra- and inter-atrial EMCD were calculated. Results: Mitral inflow velocities were studied using pulsed-wave Doppler after placing the sample volume at the leaflets’ tips. The peak early (E wave) and late (A wave) velocities were measured. The septal annular E/E’ ratio was relatively higher and lateral, septal, and right ventricular S, E’, and A’ waves were significantly lower in the HF group than in the control group (12.49±6.03 - 7.16±1.75, pE/E’ <0.0001). Intra-atrial EMCD was detected as 117.5 ms and inter-atrial EMCD as 127.5 ms in patients with prolonged atrial EMCD. A significant increase was found in prolonged intra- and inter-atrial EMCD according to functional capacity increase (p=0.012 and p=0.031, respectively). The incidence of mortality was significantly higher in patients with prolonged atrial EMCD (p=0.025), and 5 patients in the HF group died during the study over the 12-month follow-up period. Conclusions: In this study, we found a relationship between prolonged atrial conduction time and increased functional class and mortality in patients with systolic HF. © 2016 by Turkish Society of Cardiology

Extractive Dearomatization of Naphthalane Oil Fraction with Ionic Liquid and -N-Methyl-2-Pyrrolidone

In the article are given an analysis of the results of researches carried out for the purpose of selective treatment of the Naphthalane oil fraction boiling at 260-3400C with ionic liquid (IL) -morfolinphormiate synthesized on the basis formic acid + morpholine and - N-methyl-2-pyrrolidon (N-MP) and  as an extractant. The aim is to remove poisonous components -  sulfur compounds and toxic carcinogenic polynuclear aromatic hydrocarbons in order to improve therapeutic properties of Naphthalane oil cut. For this purpose we have used extraction method. On the basis of the conducted researches the role of -N-methyl-2-pyrrolidone and IL-morpholinephormiatee in extraction conditions have been determined in selective treatment of Nafthalan oil, according to the results of spectral analysis residual amount of aromatic hydrocarbons decreased from 18.5% wt accordance to 2%, 1.5%. As well as the amount of sulphur decreased from 0.0354% to 0.010%,  0.011% and 0.019%.In the next stage the treated raffinates with N-methyl-2-pyrrolidone has been purified on silica. In a result amount of aromatic hydrocarbons drastically decrease to be 0.07% and 0.02%. As a result we aquire transparency and at the same time the percentage amount of aromatic hydrocarbons drastically decreased from 2% to 0,07%, 1.5%, to 0.02%. Raffinates obtained in a 2-4 stage dearomatization with N-MP and IL. Raffinate are measured on NMR, UV and IR spectral analysis

Loss of NEDD4 contributes to RTP801 elevation and neuron toxicity: implications for Parkinson's disease

Parkinson's disease (PD) is a disorder characterized by the degeneration of certain neuronal populations in the central and peripheral nervous system. One of the hallmarks of the disease is the toxic accumulation of proteins within susceptible neurons due to major impairment in the degradation/clearance protein systems. RTP801 is a pro-apoptotic protein that is sufficient and necessary to induce neuronal death in cellular and animal models of PD. RTP801 is also upregulated in sporadic and parkin mutant PD brains. Here, we report the role of NEDD4, an E3 ligase involved in α-synuclein degradation and PD pathogenesis, in the regulation of RTP801 protein levels and toxicity. NEDD4 polyubiquitinates RTP801 in a cell-free system and in cellular cultures, and they interact physically. NEDD4 conjugates K63-ubiquitin chains to RTP801 and targets it for degradation. NEDD4 regulates RTP801 protein levels in both cultured cells and in the brain tissue. NEDD4 levels are diminished in nigral neurons from human PD brains. Interestingly, neurotoxin 6-OHDA decreases dramatically NEDD4 protein expression but elevates RTP801 protein levels. Moreover, NEDD4 protects neuronal PC12 cells from both 6-OHDA and RTP801-induced toxicity. In primary cortical neurons, NEDD4 knockdown toxicity is mediated by RTP801 since the double knockdown of RTP801 and NEDD4 abrogates the loss of phospho Ser473-Akt and the appearance of caspase-cleaved spectrin fragments. Thus, NEDD4 ligase regulates RTP801 and is sensitive to PD-associated oxidative stress. This suggests that NEDD4 loss of function in PD could contribute importantly into neuronal death by elevating RTP801

The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption

Concerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability. Binding of OligoG CF-5/20 to the bacterial cell surface was demonstrated in Gram-negative bacteria. Permeability assays revealed that OligoG CF-5/20 had virtually no membrane-perturbing effects. Lipopolysaccharide (LPS) surface charge and aggregation were unaltered in the presence of OligoG CF-5/20. Small angle neutron scattering and circular dichroism spectroscopy showed no substantial change to the structure of LPS in the presence of OligoG CF-5/20, however, isothermal titration calorimetry demonstrated a weak calcium-mediated interaction. Metabolomic analysis confirmed no change in cellular metabolic response to a range of osmolytes when treated with OligoG CF-5/20. This data shows that, although weak interactions occur between LPS and OligoG CF-5/20 in the presence of calcium, the antimicrobial effects of OligoG CF-5/20 are not related to the induction of structural alterations in the LPS or cell permeability. These results suggest a novel mechanism of action that may avoid the common route in acquisition of resistance via LPS structural modification