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Background/Aim. A substantial line of evidence indicates that Kv4.2 and Kv4.3 channels are the major components of rapid transient-outward potassium currents (A-type cur-rents). It is speculated that those currents may be involved in the maintenance of the membrane potential, as well as in the regulation of propagation and frequency of action potentials. However, very little is known about the presence and function of A-type currents in human vascular smooth muscles such as the human umbilical vein (HUV). Bearing in mind its crucial role in the proper fetal oxygenation, the aim of the study was to determine whether Kv4.2 and Kv4.3 potassium channels are present in HUV smooth muscle and to investigate potential alterations of their expression during maternal pathological conditions such as gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH). Methods. Healthy, diabetic, and hypertensive pregnancies were subjects of this investigation. Each group consisted of 6 HUV samples obtained from 6 normal pregnancies, 6 pregnancies with GDM, and 6 with PIH. After pharmacology analysis, immunohistochemistry (IH) and Western blot were performed. Results. IH revealed similar expression patterns of both, Kv4.2 and Kv4.3 subunits in HUV smooth muscle in all groups of patients. Results obtained by Western blot were in agreement with IH staining. The expression of Kv4.2 and Kv4.3 subunits were not significantly different between the groups. Conclusion. Collective-ly, this is the first study that demonstrated the presence of Kv4.2 and Kv4.3 potassium channels in the HUV smooth muscle and their preservation during GDM and PIH pregnancies. These channels are most likely major components of rapid A-type currents that may be relevant for maternal-fetus blood flow and hence fetal development. In addition, they may represent sensors for detecting hemodynamic and/or metabolic changes in the local environment. Uvod/Cilj. Značajan niz dokaza ukazuje na to da su kanali Kv4.2 i Kv4.3 glavne komponente brzih prolazno- ispravljačkih struja kalijuma (struje tipa A). Pretpostavlja se da bi te struje mogle da budu uključene u održavanje membranskog potencijala ćelije, kao i u regulaciju propagacije i učestalosti akcionih potencijala. Međutim, vrlo malo se zna o prisustvu i funkciji struje tipa A u glatkim mišićima krvnih sudova čoveka, kao što je humana umbilikalna vena (HUV). S obzirom na njenu ključnu ulogu u adekvatnoj oksigenaciji fetusa, cilj rada bio je da se utvrdi da li su podtipovi kalijumovih kanala Kv4.2 i Kv4.3 prisutni u glatkim mišićima HUV-a i da se istraže potencijalne promene njihove ekspresije tokom patoloških stanja majke – gestacijskog dijabetesa melitusa (GDM) i arterijske hipertenzije (AH) izazvane trudnoćom (AHT). Metode. U istraživanje su uključene HUV sakupljene posle trudnoće zdravih porodilja, onih čije trudnoće su bile komplikovane GDM i AH. Svaka grupa sastojala se od 6 uzoraka HUV-a dobijenih iz 6 zdravih trudnoća, 6 trudnoća komplikovanih GDM i 6 trudnoća komplikovanih AH. Nakon farmakoloških analiza, urađene su imunohistohemijska (IH) analiza i Western blot. Rezultati. Primenom IH analize pokazan je sličan obrazac ekspresije obe podjedinice Kv4.2 i Kv4.3 kanala u glatkim mišićima HUV-a u svim grupama trudnica. Rezultati dobijeni Western blot-om bili su u skladu sa IH bojenjem. Ekspresija podjedinica Kv4.2 i Kv4.3 nije se značajno razlikovala između grupa trudnica. Zaključak. Ovo je prema našim saznanjima prva studija kojom je pokazano prisustvo Kv4.2 i Kv4.3 kalijumovih kanala u glatkim mišićima HUV-a zdravih porodilja, kao i onih porodilja čija je trudnoća bila praćena prisustvom GDM ili AHT. Ti kanali su najverovatnije glavne komponente brzih struja A-tipa, koji mogu biti relevantni za protok krvi majke i ploda i na taj način delovati protektivno za razvoj fetusa. Takođe, oni mogu predstavljati senzitivne pokazatelje hemodinamskih i/ili metaboličkih promena u lokalnoj fetomaternalnoj sredini.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a phytoalexin present in a variety of plant species. Resveratrol has a wide spectrum of pharmacologic properties, and it exhibits versatile biological effects on different human and animal models. The studies have shown that potassium (K) channels can be potential targets in the mechanism of resveratrol action. K channels play a crucial role in maintaining membrane potential. Inhibition of K channels causes membrane depolarization and then contraction of smooth muscles, while the activation leads to membrane hyperpolarization and subsequently, relaxation. Five diverse types of K channels have been identified in smooth muscle cells in different tissue: ATP-sensitive K channels (KATP), voltage-dependent K channels (Kv), Ca2+ - and voltage-dependent K channels (BKCa), inward rectifier K channels (Kir), and tandem two-pore K channels (K2P). The expression and activity of K channels altered in many types of diseases. Aberrant function or expression of K channels can be underlying in pathologies such as cardiac arrhythmia, diabetes mellitus, hypertension, preterm birth, preeclampsia, and various types of cancer. Modulation of K channel activity by molecular approaches and selective drug development may be a novel treatment modality for these dysfunctions in the future. The plant-derived non-toxic polyphenols, such as resveratrol, can alter K channel activity and lead to the desired outcome. This review presents the basic properties, physiological, pathophysiological functions of K channels, and pharmacological roles of resveratrol on the major types of K channels that have been determined in smooth muscle cells.

The effect of resveratrol on vasculature of diabetic animal is not defined. This study was aimed at evaluating how alloxan-induced diabetes alters the relaxation of the isolated rat renal artery (RA) to resveratrol and determining whether prolong hyperglycemia modifies the expression of potassium (K) channels in the wall of RA. Diabetes reduced the sensitivity to resveratrol in RA. According to K channel blocker affinity, it seems that different subtype of K channels were involved in the resveratrol-induced relaxation of RA of normal rats and only voltage-sensitive Kv1 channels took part in the resveratrol effect on the RA of diabetic rats. Endothelial dysfunction developed during diabetes led to down-regulation of the expression of almost all tested K channels, while up-regulation of Kv1.3 channel expression was only noticeable. Having in mind that Kv1.3 channels have a prominent role in insulin signalling, these results suggest renovascular protective effect of resveratrol in diabetes.

Climate change is considered to have great impact on human health. The heat waves have been associated with excess morbidity and mortality of cardiovascular diseases (CVD) across various populations and geographic locations. Important role in the heat-induced cardiovascular damage has endothelial dysfunction. It has been noticed that hot weather can impair tone and structure of the blood vessels via interfering with variety of biological factors such as nitric oxide synthesize, cytokine production and systemic inflammation. Also, due to dehydration and increased blood viscosity, by promoting thrombogenesis, heat has important impact on patients with atherosclerosis. During chronic exposure to the cold or hot weather cardiovascular function can be decreased, leading to a higher risk of developing heart attack, malignant cardiac arrhythmias, thromboembolic diseases and heat-induced sepsis like shock. It has been shown that changes in the ambient temperature through increasing blood pressure, blood viscosity, and heart rate, contribute to the cardiovascular mortality. The majority of deaths due to heat waves especially affect individuals with preexisting chronic CVD. This population can experience a decline in the health status, since extreme ambient temperature affects pharmacokinetic parameters of many cardiovascular drugs. Increased mortality from ischemic or hemorrhagic stroke can also be related to extreme temperature variations. On a cellular level, higher ambient temperature can limit storage of ATP and O2 increase amount of free radicals and toxic substances and induce neuronal apoptotic signal transduction, which all can lead to a stroke. Preserving cardiovascular function in context of extreme climate changing tends to be particularly challenging.

Voltage-gated potassium (K

Gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) can jeopardize mother and/or fetus. Vascular ATP-sensitive potassium (KATP) channels most likely participate in the processes of diabetes and hypertension. The aim of this research was to examine whether GDM and PIH cause changes in the expression and function of KATP channels in vascular smooth muscle of human umbilical vein (HUV). Western blot and immunohistochemistry detected significantly decreased expression of Kir6.1 subunit of KATP channels in GDM and PIH, while the expression of SUR2B was unchanged. In GDM, a K+ channel opener, pinacidil caused reduced relaxation of the endothelium-denuded HUVs compared to normal pregnancy. However, its effects in HUVs from PIH subjects were similar to normal pregnancy. In all groups KATP channel blocker glibenclamide antagonized the relaxation of HUV induced by pinacidil without change in the maximal relaxations indicating additional KATP channel-independent mechanisms of pinacidil action. Iberiotoxin, a selective antagonist of large-conductance calcium-activated potassium channels, inhibited the relaxant effect of pinacidil in PIH, but not in normal pregnancy and GDM. Experiments performed in K+-rich solution confirmed the existence of K+-independent effects of pinacidil, which also appear to be impaired in GDM and PIH. Thus, the expression of KATP channels is decreased in GDM and PIH. In GDM, vasorelaxant response of HUV to pinacidil is reduced, while in PIH it remains unchanged. It is very likely that KATP channels modulation and more detailed insight in KATP channel-independent actions of pinacidil may be precious in the therapy of pathological pregnancies. © 2019 Elsevier Inc.

Voltage-gated potassium (Kv) channels are the largest superfamily of potassium (K) channels. A variety of Kv channels are expressed in the vascular smooth muscle cells (SMC). Studies have shown that gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) cause various changes in the human umbilical vein (HUV). Recently, we have shown that 4-AP, a nonspecific Kv1-4 channel inhibitor, significantly decreases vasorelaxation induced by K channel opener pinacidil in vascular SMCs of the HUVs from normal pregnancies, but not in GDM and PIH. The goal of this study was to provide more detailed insight in the Kv channel subtypes involved in pinacidil-induced vasodilation of HUVs, as well as to investigate potential alterations of their function and expression during GDM and PIH. Margatoxin, a specific blocker of Kv1.2 and Kv1.3 channels, significantly antagonized pinacidil-induced vasorelaxation in normal pregnancy, while in HUVs from GDM and PIH that was not the case, indicating damage of Kv1.2 and Kv1.3 channel function. Immunohistochemistry and Western blot revealed similar expression of Kv1.2 channels in all groups. The expression of Kv1.3 subunit was significantly decreased in PIH, while it remained unchanged in GDM compared to normal pregnancy. Phrixotoxin, specific blocker of Kv4.2 and Kv4.3 channels, did not antagonize response to pinacidil in any of the groups. The major novel findings show that margatoxin antagonized pinacidil-induced relaxation in normal pregnancy, but not in GDM and PIH. Decreased expression of Kv1.3 channels in HUV during PIH may be important pathophysiological mechanism contributing to an increased risk of adverse pregnancy outcomes.

86th Congress of the European-Atherosclerosis-Society (EAS), Lisbon,PORTUGAL, MAY 05-08, 2018

85th Congress of the European-Atherosclerosis-Society (EAS), Apr 23-26, 2017, Prague, Czech Republic

BACKGROUND: /Aim. There are only several studies on the acute effect of alcoholic drinks intake on heart rhythm and this phenomenon is still not well understood. We wanted to examine whether linear and nonlinear measures of RR interval and QT interval series could quantify the effect of beer in healthy subjects. Methods. Eighteen young volunteers drank 500 mL of beer (21 g of ethanol). Electrocardiogram (ECG) recordings were taken in supine position: 20 minutes before (relaxation) and 60 minutes after drink intake. The RR interval series and the QT interval series were extracted from ECG and we calculated short-term (α1) and long-term (α2) scaling exponents and sample entropy (SampEn) for both series; low frequency (LF) and high frequency (HF) spectral components from RR interval series and QT variability (QTV). Blood pressure was measured every 10 minutes. Results. It was shown that beer induced changes in variability and correlation properties of these series. Immediate effect of beer intake was detected as a transient increase in the QT variability, heart rate and blood pressure. Delayed effects of beer were shortening of the RR and QT intervals and reduction of the HF spectral component. Beer intake also increased short-term scaling exponent (α1) of the RR time series and long-term scaling exponent (α2) of the QT time series. Conclusion. Our results suggest that acute effects of beer are reduced parasympathetic control of the heart and changed dynamic complexity of the ventricular repolarization. Uvod/Cilj. Akutni efekat uzimanja alkoholnih pića na kardiovaskularne ritmove je fenomen koji još uvek nije dovoljno razjašnjen i u literaturi postoji svega nekoliko radova na tu temu. Cilj rada je bio da se ispita da li se linearnim i nelinearnim merama nizova RR i QT intervala može kvantifikovati akutni efekat male količine piva kod zdravih osoba. Metode. Osamnaest mladih zdravih muškaraca je pilo po 500 mL piva (21 g etanola). Elektrokardiogram (EKG) je beležen u ležećem položaju: 20 minuta pre (u relaksaciji) i 60 minuta neposredno posle uzimanja pića. Iz digitalizovanog zapisa EKG-a izdvojeni su nizovi RR i QT intervala. Iz oba niza smo izračunali kratkodometni (α1) i dugo-dometni skalirajući eksponent (α2), kao i entropiju uzorka (SampEn). Iz nizova RR intervala određene su spektralne komponente niskofrekventnih (LF) i visokofrekventnih (HF) opsega, a iz nizova QT intervala varijabilnost QT intervala (QTV). Krvni pritisak je bio meren svakih 10 minuta. Rezultati. Pokazali smo da pivo menja varijabilnost i korelacione osobine ovih nizova. Neposredni efekat uzimanja piva ogleda se u prolaznim povećanjima QT varijabilnosti, srčane frekvence i krvnog pritiska, a produženi u skraćenju dužine RR i QT intervala i smanjenju spektralne komponente HF. Uzimanje piva je takođe dovelo do porasta kratkodometnog skalirajućeg eksponenta (α1) RR niza i dugodometnog skalirajućeg eksponenta (α2) QT niza. Zaključak. Akutni efekat uzimanja piva je redukovana parasimpatička kontrola srca i izmenjena kompleksnost dinamike ventrikularne repolarizacije.

In order to provide guidance data for clinically rational use of an antibiotics consuption, prescribing and prevalence of multidrug resistant (MDR) Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii were monitored on the surgical (S) and medical (M) wards of the University Hospital Center "Dr. Dragisa Misovic-Dedinje" (Belgrade, Serbia), in the study period from 2012 to 2015. Appropriateness of antimicrobial use was evaluated using the Global-Prevalence Survey method designed by the University of Antwerp. The percentages of MDR pathogens relative to the total number of isolates of K. pneumoniae and P. aeruginosa were higher on the S (86.2% and 49.1%) than on the M (63.2% and 36.9%) wards. The percentage of MDR A. baumannii was not different between S (93.7%) and M (79.5%) wards. An overall antibiotics consumption (defined daily doses/100 bed-days) during study was 369.7 and 261.5 on the S and M wards, respectively. A total of 225 prescriptions of antimicrobials were evaluated in138 adults admitted to wards on the day of the survey. The percentage of antimicrobials prescribed for prophylaxis on the M and S wards were 0% and 25%, respectively. Therapies were more frequently empiric (S, 86.8% and M, 80%). The percentages of medical errors on the S and M wards were 74.6% and 27.3%, respectively. The quality indicators for antibiotic prescribing on the S and M wards were as follows: the incorrect choice of antimicrobials (35.6% vs. 20.0%), inappropriate dose interval (70.6% vs. 16.9%) or duration of therapy (72.5% vs. 23.1%), a non-documented stop/review data (73.6% vs. 16.9%) and divergence from guidelines (71.9% vs. 23.1%). Treatment based on biomarkers was more common on the M wards as compared to the S wards. The increasing prevalence of MDR pathogens, a very high consumption and incorrect prescribing of antimicrobials need special attention, particularly on the S wards.

Resveratrol is a phytoalexin produced in a number of plant species including grapes. The benefit of resveratrol to health is widely reported. Resveratrol has been found to promote relaxation of non-pregnant and pregnant uterus, but its mechanism of action is unclear. The aims of our study were to investigate the involvement of inwardly rectifying potassium channels (Kir) in inhibitory effects of resveratrol on three models of contractions of non-pregnant rat uterus: the spontaneous rhythmic contractions (SRC), oxytocin-elicited phasic contractions and tonic oxytocin-elicited contractions.Uterine strips were obtained from virgin female Wistar rats in oestrus. Strips were mounted into organ bath for recording isometric tension in Krebs-Ringer solution. Experiments followed a multiple curve design. In order to test the involvement of Kirchannels in a mechanism of action of resveratrol(1-100 μM),BaCl2 (1 mM),a antagonist of inwardly rectifying pota­ssium channels was used. Resveratrol induced a concentration-dependent relaxation of all models of contractions. BaCl2 antagonized the response to resveratrolon SRC and oxytocin-elicited phasic contractions. Relaxation achieved by resveratrolon tonic oxytocin-elicited concentrations was insensitive to BaCl2.The antagonism of resveratrol effects by inwardly rectifying potassium channels antagonist suggests that Kir channels are involved in resveratrol action on phasic contractions of rat uterus. Inhibitory effect of resveratrol on tonic contractions did not include Kir channels. [Projekat Ministartsva nauke Republike Srbije, br. TR31020]

We study the storage of coherences in atomic rubidium vapor with a three-level coupling scheme with two ground states and one electronically excited state driven by one optical (control) and one radio frequency field. We initially store an atomic ground state coherence in the system. When retrieving the atomic coherence with a subsequent optical pulse, a second (signal) optical beam is created whose difference frequency to the control field is found to be determined by the atomic ground state's Raman transition frequency.