Fractal nature of benzene stacking interactions.

CONTEXT: Benzene and other aromatic groups, as planar groups with [Formula: see text] electrons cloud, tend to form stacking interactions which have an important role in various chemical and biological processes. In order to have a better insight in the nature of these interactions, we have performed a fractal analysis on patterns of electron density and electrostatic potential for two benzenes in stacking interaction. The calculated fractal dimension follows the trend of the calculated interaction energy for the interplanar distances of 4.0 to 6.0 Å, which partially coincides with the strongest attractive stacking interactions. The fractal dimension vs. energy dependences were fitted with the logistic curve, and the fitting coefficient was 0.96 up to 1.00. METHODS: For the benzene stacking interaction energy, with a range of conformations and distances between two benzenes, DFT calculations at the B3LYP+D3/aug-cc-pVDZ level were performed with the TURBOMOLE software. The fractal analysis for electron density and electrostatic potential has been done by python scripting.

Orchestrating aquaporin-4 and connexin-43 expression in brain: Differential roles of α1- and ß1-syntrophin.

Aquaporin-4 (AQP4) water channels and gap junction proteins (connexins) are two classes of astrocytic membrane proteins critically involved in brain water and ion homeostasis. AQP4 channels are anchored by α1-syntrophin to the perivascular astrocytic endfoot membrane domains where they control water flux at the blood-brain interface while connexins cluster at the lateral aspects of the astrocytic endfeet forming gap junctions that allow water and ions to dissipate through the astrocyte syncytium. Recent studies have pointed to an interdependence between astrocytic AQP4 and astrocytic gap junctions but the underlying mechanism remains to be explored. Here we use a novel transgenic mouse line to unravel whether ß1-syntrophin (coexpressed with α1-syntrophin in astrocytic plasma membranes) is implicated in the expression of AQP4 isoforms and formation of gap junctions in brain. Our results show that while the effect of ß1-syntrophin deletion is rather limited, double knockout of α1- and ß1-syntrophin causes a downregulation of the novel AQP4 isoform AQP4ex and an increase in the number of astrocytic gap junctions. The present study highlight the importance of syntrophins in orchestrating specialized functional domains of brain astrocytes.

Potential New Approaches in Predicting Adverse Cardiac Events One Month after Major Vascular Surgery.

OBJECTIVE: The aim of our study was to find the best model with sufficient power to improve the risk stratification in major vascular surgery patients during the first 30 days after this procedure. The discriminatory power of 4 biomarkers (troponin I [TnI], N-terminal prohormone of brain natriuretic peptide [NT-proBNP], creatine kinase-MB isoenzyme [CK-MB], high-sensitivity C-reactive protein [hs-CRP]) was tested as well as 2 risk assessment models and 13 different combinations of them. SUBJECTS AND METHODS: The study included 122 patients (77% men, 23% women) with an average age of 67.03 ± 4.5 years. An aortobifemoral bypass was performed in 6.56% of the patients, a femoropopliteal bypass in 18.85%, and 49.18% received open surgical reconstruction of the carotid arteries. A total of 25.41% of the patients were given an aortobi-iliac bypass. RESULTS: During the first 30 days, 13 patients (10.7%) had 17 cardiac complications. The most common complication was the new onset of atrial fibrillation (35.3%). During the first 10 days, 10 patients had 1 complication and 2 patients had 2 cardiac events, while 1 patient had 3 complications. By comparing combinations of scores and markers, it was shown that revised cardiac risk index (RCRI) + Vascular Portsmouth Physiological and Operative Severity Score (V-POSSUM) + hsTnI and RCRI + V-POSSUM + hsTnI + NT-proBNP with 100% sensitivity, > 80% specificity had the best discriminatory ability (AUC 0.924 and 0.933, respectively; p < 0.001 for both models) for cardiac complications during the 30 days after surgery. CONCLUSION: Combinations of traditional preoperative risk factors and scores can enhance the assessment of major adverse cardiac events (MACE) in patients preparing for large vascular surgery. Using only one risk score in these patients seems to be underperforming in preoperative risk assessment.

An unexpected negative inotropic effect of prostaglandin F2alpha in the rat heart.

Prostaglandin F(2alpha) (PGF(2alpha)) is produced during myocardial inflammation and many of the insults that trigger contractile dysfunction also activate prostaglandin synthesis and production. However, although PGF(2alpha) plays a significant role in the cardiac response to inflammation, the effect of this particular compound on the heart was largely studied at the cellular level and probably no due attention was paid to the effect of PGF(2alpha) on the whole heart contractility. Therefore, in the present study we have investigated the effect of PGF(2alpha) on isolated right ventricle of the rat heart. PGF(2alpha) (1nM-1microM) induced concentration-dependent decrease of the amplitude of contractions of the ventricular muscle. Real time RT-PCR has revealed that prostaglandin FP receptors are expressed in the rat myocardium and the level of expression was similar to those of creatine kinase and adenylate kinase, which are proteins abundantly present in the heart. An antagonist of FP receptors, PGF(2alpha) dimetilamide (10nM), abolished negative inotropic effect induced by PGF(2alpha). To examine the possibility that PGF(2alpha) could activate non-FP prostaglandin receptor, we have measured the level of expression of all known prostaglandin receptors in the rat heart. These experiments have shown that the order of expression of prostaglandin receptors in the rat heart is FP>>EP1=TP>EP4>EP3>DP=IP. Based on the obtained results we conclude that PGF(2alpha) induces negative inotropic effect on rat heart by activating FP prostaglandin receptors. This effect of PGF(2alpha) could contribute to cardiac dysfunction in conditions of systemic and myocardial inflammation.

High glucose protects single beating adult cardiomyocytes against hypoxia.

In the heart, the opening of sarcolemmal ATP-sensitive K(+) (K(ATP)) channels seems to be crucial for the cardiac protection against hypoxia/ischaemia. In the present study, we have exposed cardiomyocytes under hypoxia to high extracellular glucose (30 mM). Under these conditions, intracellular concentration of 1,3-bisphosphoglycerate has increased confirming stimulation of glycolysis. Perforated patch-clamp electrophysiology revealed that hypoxia induces whole-cell K(+) current in cardiomyocytes more efficiently in the presence than in the absence of high glucose. Glucose significantly promoted survival of cardiomyocytes exposed to hypoxia. HMR 1098, an antagonist of sarcolemmal K(ATP) channels, inhibited glucose-induced activation of whole-cell K(+) current during hypoxia as well as glucose-mediated cytoprotection. An inhibitor of glyceraldehyde 3-phosphate dehydrogenase, iodoacetate, inhibited glycolysis in hypoxia and blocked the activation of sarcolemmal K(ATP) channels. Based on the obtained results, we conclude that the activation of sarcolemmal K(ATP) channels is involved in glucose-mediated cardioprotection.