Sildenafil (Viagra) is a vasodilator mainly used in the treatment of erectile dysfunction. Atrial or ventricular fibrillation may rarely occur as a side effect during sildenafil therapy. Although changes in inward rectifier potassium currents including IK1 are known to contribute to the pathogenesis of fibrillation, the effect of sildenafil on IK1 has not been studied. In experiments, Ba2+ is used as a specific inhibitor of IK1 at high concentrations (usually 100 µM). Being an environmental contaminant, it is also present in the human body; Ba2+ plasmatic concentrations up to 1.5 µM are usually reported in the general population. This study was primarily aimed to investigate changes of IK1 induced by sildenafil in a wide range of concentrations (0.1–100 µM). Additionally, the effect of combination of sildenafil and Ba2+ at selected clinically-relevant concentrations was tested, at 0.1 µM both on IK1 and on the action potential duration (APD). Experiments were performed by the whole-cell patch-clamp technique on enzymatically isolated rat ventricular cardiomyocytes, mostly at 23°C with the exception of APD measurements which were performed at 37°C as well. Sildenafil caused a significant, reversible, and concentration-dependent inhibition of IK1 that did not differ at −50 and −110 mV. Simultaneous application of sildenafil and Ba2+ at 0.1 µM revealed a massive inhibition of both inward and outward components of IK1 (this synergy was missing at other tested combinations). The combined effect at 0.1 µM (45.7 ± 5.7 and 43.0 ± 6.9% inhibition at −50 and −110 mV, respectively) was significantly higher than a simple sum of almost negligible effects of the individual substances and it led to a significant prolongation of APD at both 23 and 37°C. To our knowledge, similar potentiation of the drug-channel interaction has not been described. The observed massive inhibition of IK1 induced by a combined action of the vasodilator sildenafil and environmental contaminant Ba2+ at a low concentration and resulting in a significant APD prolongation may contribute to the genesis of arrhythmias observed in some patients treated with sildenafil.
The size of the shadow banking sector (SBS) has more than doubled in the Czech Republic over the last decade. This places a potential burden on policy makers. On the one hand, the SBS complements regular banking by expanding access to credit and investments, enabling better risk sharing and maturity transformation, and supporting market liquidity. On the other hand, SBS activities can put the stability of the financial system at risk and amplify its procyclicality by exacerbating the buildup of leverage and asset price bubbles. We implement a FAVAR model of the Czech economy to determine the impact of macroeconomic factors on the SBS. We find that the SBS: (i) is sensitive to changes in market interest rates and term spread; (ii) exhibits great procyclicality; (iii) can act as a complement to regular banking and satisfy some additional demand for credit. We also define some potential risks of continued growth of the SBS, linked to our empirical evidence.
Mar tin Machá èek, Eva Kol cu no vá, Vy so ká ško la báò ská -Tech nic ká uni ver zi ta, Os t ra va* ÚvodUž i v èes ké aka de mic ké ko mu ni tì eko no mù se po ma lu za byd lu jí žeb øíè ky se sta vo va né za úèe lem ob jek ti vi za ce pro ce su hod no ce ní vì dec ké ho vý ko nu a vli vu jed not liv cù a pra coviš•. Da niel Mü nich se sice mýlí když tvr dí, že "The only existing stu dy pre sen ting pu b licati on ran kings of Czech eco no mists is (Tur no vec, 2005)" (Mü nich, 2006, s. 523), je však prav dou, že star ší stu die byly zpra co vá ny pod stat nì jed no duš ší me to di kou a vy chá ze ly z velmi omezené publikaèní databáze (viz Macháèek, Kolcunová, 2004).Spo leè ným jme no va te lem do sud vznik lých tu zem ských žeb øíè kù je za mì øe ní se na použití tra diè ních jed no èí sel ných bib li o me t ric kých uka za te lù, kon krét nì po ètu ci ta cí vì -dec kých pra cí a/nebo po ètu vì dec kých pu b li ka cí. Uka za te le typu "cel ko vý po èet ci ta cí", "prù mìr ný po èet ci ta cí na pu b li ka ci", "po èet ci ta cí vý znam nì ci to va ných pu b li ka cí", (im pakt ní mi fak to ry) vážený sou èet ci ta cí èili "ci taè ní skóre", "cel ko vý po èet pu b li ka cí", "po èet vý znam nì ci to va ných pu b li ka cí" nebo (im pakt ní mi fak to ry) vážený sou èet pu b lika cí èili "pu b li kaè ní skóre" vy ka zu jí øadu pøed nos tí, stej nì tak ale i øadu ne do stat kù. Je napø. zøej mé, že vel ké ho po ètu ci ta cí lze do sáh nout uve øej nì ním tøe ba jen je di né ho, vy soce kon tro verz ní ho èlán ku v celé aka de mic ké ka ri é øe. Ob dob nì pla tí, že znaè ný po èet pu bli ka cí mùže zna me nat pou hou hro ma du pro vìdu zøej mì bez vý znam ných, pro tože ne ci to va ných pa pí rù. Ani pu b li ko vá ní v pe ri o di cích s vý raz nì klad ným im pakt ním fak torem (IF) není au to ma tic kou zá ru kou vì dec ké vý znam nos ti prá ce, nebo• tìm to pe ri o dikùm k je jich IF na po má há jen re la tiv nì málo vy so ce ci to va ných èlán kù z mno ha uve øej nì ných. Jak uvá dí v této sou vis los ti aktuálnì Oswald (2007), "the best article in an issue of a good to medium-quality journal routinely goes on to have much more citations impact than a ´poor´ article published in an issue of a more prestigious journal" (s. 22).Žádný ide ál ní bib li o me t ric ký uka za tel vì dec ké ho vý ko nu èi vli vu ne e xis tu je. Pøi se stavo vá ní od po ví da jí cích žeb øíè kù je pro to nou zo vým øe še ním buï kom bi no vá ní bìžnì používa ných uka za te lù, nebo spo lé há ní se na nì ja ký novì vy tvo øe ný uka za tel s ne tra diè ní -mi vlast nost mi. K prv ní možnos ti se uchý lil Fran ti šek Tur no vec (2005), kte rý spo jil již zmí -nì ná ci taè ní a pu b li kaè ní skóre v cel ko vé skóre. Dru hou možnost využili Cah lík a Pes sro vá (2006), resp. Ma chá èek a Kol cu no vá (2006), kte øí pi o nýr sky apli ko va li tzv. Hirschovo èíslo (index) pøi analýze ekonomického výzkumu v Èeské republice (ÈR). Co je to Hirschovo èíslo a o èem jeho hodnota vypovídá? O tom struènì pojednává další èást èlánku, jenž je jako celek v...
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