/Ca2+ exchanger (NCX) activity may play a crucial role in cardiac arrhythmogenesis; however, data regarding the anti-arrhythmic efficacy of NCX inhibition are debatable. Feasible explanations could be the unsatisfactory selectivity of NCX inhibitors and/or the dependence of the experimental model on the degree of Ca 2+ i overload. Hence, we used NCX inhibitors SEA0400 and the more selective ORM10103 to evaluate the efficacy of NCX inhibition against arrhythmogenic Ca 2+ i rise in conditions when [Ca 2+ ]i was augmented via activation of the late sodium current (INaL) or inhibition of the Na EXPERIMENTAL APPROACHAction potentials (APs) were recorded from canine papillary muscles and Purkinje fibres by microelectrodes. NCX current (INCX) was determined in ventricular cardiomyocytes utilizing the whole-cell patch clamp technique. Ca KEY RESULTSEnhanced INaL increased the Ca 2+ load and AP duration (APD). SEA0400 and ORM10103 suppressed INCX and prevented/reversed the anemone toxin II (ATX-II)-induced [Ca 2+ ]i rise without influencing APD, CaT or cell shortening, or affecting the ATX-II-induced increased APD. ORM10103 significantly decreased the number of strophanthidin-induced spontaneous diastolic Ca 2+ release events; however, SEA0400 failed to restrict the veratridine-induced augmentation in Purkinje-ventricle APD dispersion. CONCLUSIONS AND IMPLICATIONSSelective NCX inhibition -presumably by blocking revINCX (reverse mode NCX current) -is effective against arrhythmogenesis caused by [Na]i elevation, without influencing the AP waveform. Therefore, selective INCX inhibition, by significantly reducing the arrhythmogenic trigger activity caused by the perturbed Ca 2+ i handling, should be considered as a promising anti-arrhythmic therapeutic strategy.
6This 8-week, randomized, double-blind, controlled study compared efficacy and tolerability of telmisartan ⁄ amlodipine (T ⁄ A) single-pill combination (SPC) vs the respective monotherapies in 858 patients with severe hypertension (systolic ⁄ diastolic blood pressure [SBP ⁄ DBP] !180 ⁄ 95 mm Hg). At 8 weeks, T ⁄ A provided significantly greater reductions from baseline in seated trough cuff SBP ⁄ DBP ()47.5 mm Hg ⁄ )18.7 mm Hg) vs T (P<.0001) or A (P=.0002) monotherapy; superior reductions were also evident at 1, 2, 4, and 6 weeks. Blood pressure (BP) goal and response rates were consistently higher with T ⁄ A vs T or A. T ⁄ A was well tolerated, with less frequent treatmentrelated adverse events vs A (12.6% vs 16.4%) and a numerically lower incidence of peripheral edema and treatment discontinuation. In conclusion, treatment of patients with substantially elevated BP with T ⁄ A SPCs resulted in high and significantly greater BP reductions and higher BP goal and response rates than the respective monotherapies. T ⁄ A SPCs were well tolerated. J Clin Hypertens (Greenwich). 2012;14:206-215. Ó2012 Wiley Periodicals, Inc.Based on evidence from a number of large antihypertensive trials, 1-9 most guidelines acknowledge that combination therapy is needed to reduce blood pressure (BP) successfully to goal in the majority of patients; only a minority of patients achieve their BP goal with a single agent.10-14 Also, the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) study showed a significant reduction of cardiovascular (CV) events and death in hypertensive patients at high CV risk treated with a combination of an angiotensin-converting enzyme (ACE) inhibitor and a calcium channel blocker (CCB).15 Nevertheless, despite rigorous and comprehensive guidelines, and a trend towards an increase in the use of combination therapy in treatment practice, 16 several studies have demonstrated the persistence of poor BP goal rates in treated patients. [17][18][19] The impact of poor BP control is compounded by the often high prevalence of other CV risk factors in hypertensive patients (eg, hypercholesterolemia, obesity, type 2 diabetes mellitus [T2DM], and smoking).13 Therefore, an urgent need still remains to improve the management of hypertension. One logical approach would be to use 2 drugs from different classes and complementary mechanisms of action in combination. Such combinations may result in additional BP decreases and improved goal rates, compared with either agent used alone. 20-23Furthermore, single-pill combinations (SPCs) are known to increase treatment adherence and reduce health care costs. [24][25][26][27] A combination of a CCB and an angiotensin II receptor blocker (ARB) is a rational approach for managing hypertension and there is increasing evidence that this combination is effective. 11,13,28,29 The aim of the current study was to compare the efficacy and tolerability of the SPC of telmisartan 80 mg ⁄ amlodipine 10 mg (T80 ⁄ A10) with that of...
A novel material, a conducting composite with variable temperature coefficient of electrical conductivity, was prepared in a propagating front of an addition polymerization. Graphite and zinc particles were incorporated into an acrylamide-triethylene glycol dimethacrylate copolymer. Specific electric resistance values of the materials yielded were measured at room temperature and also conductivity measurements were performed in the range of 20-220°C. The basic recipe was modified by doping the conductive composite materials with microscopic-scale-size particles of several inorganic and organic compounds, resulting in significantly different conductivity features of the composite. Scanning electron microscopy was performed to study the morphology of materials yielded. No percolative patterns containing zinc particles were found to support the conductive behavior of the composite. In accordance with to the modifying effect of doping materials we suspect that the acrylamide-triethylene glycol dimethacrylate copolymer plays a specific role in the electric conductivity behavior of the composite material. ZUSAMMENFASSUNG:Ein neues elektrisch leitfahiges Verbundmaterial mit variablem Temperaturkoeffizient der elektrischen Leitfahigkeit wurde durch eine ,,propagating front"-Copolymerisation von Acrylamid und Triethylenglykoldimethacrylat in Gegenwart von Graphitund Zinkpartikeln hergestellt. Der spezifische elektrische Widerstand der Polymeren wurde bei Raumtemperatur bestimmt; Leitfahigkeitsmessungen wurden zwischen 20 und 220 "C durchgefiihrt. Die Leitfahigkeitseigenschaften der Copolymeren wurden durch Dotierung mit mikroskopischen Teilchen einiger organischer und anorganischer Substanzen modifiziert. Die Morphologie der Composite wurde mit der Rasterelektro-* Correspondence authors. 0 1996 Hiithig & Wepf Verlag, Zug CCC OOO3-3146/96/$07.00 J. Szalay, I. P. Nagy, I. Barkai, M. Zsuga nenmikroskopie untersucht. Dabei wurden keine das Leitfahigkeitsverhalten beeinflussende zinkhaltigen Perkolationsstrukturen gefunden. Es wird vermutet, daB das Acrylamid/Triethylenglykoldimethacrylat-Copolymere eine entscheidende Rolle im elektrischen Leitfahigkeitsverhalten der Verbundmaterialien spielt.
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