Efekti pinacidila - otvarača kalijumovih kanala na kontrakcije izolovanog negravidnog uterusa pacova izazvane kalijum hloridom

The effects of K+ channel opener, pinacidil on contractions provoked by contraction-stimulating KCl were investigated on isolated uterus of non-pregnant rats in oestrus. Pinacidil produced a more potent inhibition of 20 mM KCl-elicited contractions (pD2 = 6.57 μM) than of 40 or 80mMKCl-elicited contractions (pD2=5.11 and 5.19 μM, respectively). Glibenclamide, a selective blocker of adenosine triphosphate (ATP)-sensitive K+ (KATP) channels, antagonized the pinacidil-induced inhibition of contractions elicited by 20 mM KCl in a competitive manner. However, the pinacidil-induced inhibition of contractions provoked by 40 and 80 mM KCl glibenclamide was unable to prevent them. Pinacidil ability to completely relax the non-pregnant uterus pre-contracted with K+-rich solution suggests that K+ channelindependent mechanism(s) also plays a part in its relaxant effect.U ovom radu su prikazani efekti pinacidila, koji ima osobinu da otvara kalijumove kanale, na kontrakcije izazvane kalijum hloridom na modelu izolovanog negravidnog uterusa ženki pacova tokom estrusa. Pinacidil dovodi do snažnije inhibicije kontrakcija izazvanih sa 20mM KCl (pD2= 6.57 μM) u poređenju sa kontrakcijama izazvanim sa 40 ili 80 mM KCl (pD2 = 5.11 i 5.19 μM). Poznato je da je glibenclamid selektivni blokator adenozin-3-fosfat senzitivnih K+ (KATP) kanala antagonizuje pinacidilom indukovanu kompetitivnu inhibiciju kontrakcija izazvanih pomoću 20 mM KCl-a. Međutim, pinacidilom indukovana inhibicija kontrakcija, izazvanih sa 40 i 80 mM KCl-a nije se mogla prevenirati glibenclamidom. Sposobnost pinacidila da dovede do potpune relaksacije negravidnog uterusa ženki pacova pre kontrakcije izazvane rastvorom kalijuma ukazuje na to da u relaksaciji učestvuje i mehanizam nezavisan od kalijumovih kanala

Antiaritmički efekti novosintetisanih derivata propafenona

It is well known that the presence of different chemical groups in drug molecules influences their pharmacological properties. The aim of our study is to investigate whether newly synthesized derivatives of propafenone, with changes in benzyl moiety, have a different effect upon arrhythmia, compared to propafenone. 5OCl-PF and 5OF-PF are derivatives of propafenone with-Cl or –F substituent on the ortho position of the benzyl moiety. For verification of their antiarrhythmic effect, we used an in vivo rat model of aconitine-induced arrhythmia. 5OCl-PF speeded the appearance of supraventricular premature beats (SVPB) and death more than aconitine. All animals treated with 5OCl-PF developed ventricular premature beats in salvos (VPBS), bigeminies (VPBB) and paroxysmal ventricular tachycardia (PVT). 5OF-PF had a negative chronotropic effect and potentiated atrial excitability (more SVPB). It had a positive effect on the occurrence and onset time of supraventricular tachycardia, VPBS, and PVT. Based on the obtained results, it can be concluded that newly synthesized propafenone derivatives have no better antiarrhythmic effect than the parent compound. In the future, our research will be focused on the synthesis of different derivatives and examining their antiarrhythmic effects.Dobro je poznato da prisustvo različitih hemijskih grupa u molekulima leka utiče na njegova farmakološka svojstva. Cilj našeg istraživanja je ispitati da li novosintetisani derivati propafenona, s promenama u benzilnoj grupi, imaju drugačiji efekat na aritmiju u odnosu na propafenon. 5OCl-PF i 5OF-PF su derivati propafenona sa -Cl ili –F supstituentom na orto položaju benzilnog dela. Za proveru njihovog antiaritmičnog efekta koristili smo in vivo model na pacovima sa aritmijom izazvanom akonitinom. 5OCl-PF je ubrzao pojavu supraventrikularnih prevremenih otkucaja (SVPB) i smrt više nego akonitin. Sve životinje lečene sa 5OCl-PF razvile su ventrikularne prevremene otkucaje (VPBS i VPBB) i paroksizmalnu ventrikularnu tahikardiju (PVT). 5OF-PF je imao negativan hronotropni efekat i potencirao atrijalnu ekscitabilnost (više SVPB). Pozitivno je uticao na pojavu i vreme početka supraventrikularne tahikardije, VPBS i PVT. Na osnovu dobijenih rezultata se može zaključiti da novosintetisani derivati propafenona nemaju bolji antiaritmijski efekat od polaznog jedinjenja. U budućnosti, istraživanje će biti usmereno ka sintezi hemijski drugačijih derivata i ispitivanju njihovog antiaritmijskog efekta

Extraction Kinetic of Some Phenolic Compounds During Cabernet Sauvignon Alcoholic Fermentation and Antioxidant Properties of Derived Wines

In this study, we estimated the usage of Cabernet Sauvignon in microvinifications, obtaining wines with increased phenolic compound content. Kinetic extraction of phenolic compounds during alcoholic fermentation was affected by maceration time (3, 5, 7, 14 and 21 days) and the addition and kinetics of enzyme preparations (EP). The highest extraction rates were observed for catechin (EXV EP – EXV en-zyme preparation and CP EP – Color plus enzyme preparation) and p-hydroxybenzoic acid (Car EP - Ca-ractere enzyme preparation). According to extraction time of the analyzed phenolic compounds, maximal values (ellagic acid, ferulic acid, chlorogenic acid, caffeic acid, naringenin, p-hydroxybenzoic acid, p-coumaric acid, protocatechuic acid, trans-resveratrol, syringic acid, vanillin, and vanillic acid) were ob-tained on day 15 of maceration with addition of CP EP, with exceptions of gallic acid, catechin, and my-ricetin. Prolonged maceration times, up to 21 days, showed the most potent DPPH free radical scavenging activity with Car EP and the highest Ferric Reducing Ability of Plasma (FRAP) values with CP EP

Ispitivanje markera krvlju prenosivih bolesti, algoritama testiranja i preventivnih mera

Introduction/Aim The most common blood borne diseases or transfusion transmitted infections (TTI) are hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Numerous tests are used to prove the presence of these viruses indirectly (by detecting antibody presence - ELISA and CLIA) or directly (by detecting the presence of viral genome - NAT-PCR and LCR).To present a two-year analysis of testing for blood borne disease markers in pregnant women, patients preparing for surgery procedures and people with high-risk behavior (HBs Ag, anti-HCV and anti-HIV) at the Belgrade City Institute for Public Health and adopting measures for their prevention. Methodology During the two-year period, 11,983 pregnant women and 934 people with high-risk behavior were tested. Preliminary testing for HBs antigen, anti-HCV antibodies and anti-HIV antibodies was performed with 3rd generation ELISA tests ("Hepanostika HBsAg Uni-Form II", "Vironostika HIV Uni-Form II Ag / Ab" ; "The bioMérieux Clinical Diagnostics," manufactured in France; "Hepanostika HCV Ultra" is manufactured by "Beijing United Biomedical Co.Ltd.", China and the other two are manufactured in France). Primarily positive blood samples were tested again with the same test (in a duplicate procedure) on a new sample which was placed in a "dry" tube with no anticoagulant 10-14 days after being primarily positive for TTI markers. Those samples were also tested with a WB "Western Blot" confirmatory test - WB ("INNO-LIA HCV Ab III"; INNO-LIPA HBV Genotyping "and" INNO-LIA HIV I / II"). "Innogenetics NV ", Belgium is the manufacturer of all three confirmatory tests. Blood samples with positive results on the confirmatory tests for TTI were accepted as positive for HBs Ag, anti-HCV or anti-HIV. Results From 11,983 tested pregnant women, 152 (1.27%) were preliminarily reactive to HBsAg, 38 (0.32%) were confirmed positive for HBsAg and 114 (0.95%) were false reactive to HBsAg; 123 (1.03%) were preliminarily reactive to anti-HCV, 35 (0.29%) pregnant women were confirmed positive for antiHCV and 88 (0.74%) were false reactive for anti-HCV; and 15 (0.13%) pregnant women were preliminarily reactive to anti-HIV, 5 (0.04%) pregnant women were confirmed positive for anti-HIV and 10 (0.09%) were false reactive to anti-HIV. From 934 tested individuals with high-risk behavior 36 (3.85%) were preliminarily reactive to HBs Ag, 28 (2.99%) were confirmed positive for HBsAg and 8 (0.86%) were false reactive to HBsAg; 38 (4.07 %) were preliminarily reactive to anti-HCV, 33 (3.53%) were confirmed positive for anti-HCV and 5 (0.54%) false reactive to anti-HCV and 10 (1.07%) were preliminarily reactive to anti-HIV, 9 (0.96%) were confirmed anti-HIV positive and 1(0.11%) was false reactive to anti-HIV. Conclusion The results of our study showed a higher prevalence of HBsAg, anti-HCV and anti-HIV in people with high-risk behavior than in pregnant women. There are more false reactive results in pregnant women than in people with high-risk behavior. Preventive measures would include broader education on ways blood borne diseases are transmitted, testing blood and blood products with the latest generation of tests and correct execution of medical interventions with special attention on principles of asepsis and antisepsis.Uvod/cilj Najčešće krvlju prenosive bolesti ili transfuzijske transmisivne infekcije (TTI) su hepatitis tipa B i C i virus humane imunodeficijencije (HIV). Brojnim testovima može se dokazati njihovo prisustvo u krvi indirektnim (prisustvo antitela - ELISA i CLIA) ili direktnim putem (prisustvo genoma virusa NAT PCR i LCR). Cilj rada je analiza testiranja na markere krvlju prenosivih bolesti kod trudnica, pacijenata koji se pripremaju za planirane hirurške procdure i osobe sa rizičnim ponašanjem na prisustvo virusa (HBs Ag, anti-HCV i anti-HIV) sprovedenog u Gradskom zavodu za javno zdravlje u Beogradu i upoznavanje sa preventivnim merama za njihovo suzbijanje. Metod rada U dvogodišnjoj studiji testirano je 11.983 trudnica i 934 osoba sa rizičnim ponašanjem. Preliminarno testiranje na HBs Ag, antitela anti-HCV i anti-HIV, vršeno je ELISA testom treće generacije. Preliminarno pozitivni uzorci krvi ponovno su testirani istim testom iz novog uzorka, nakon 10-14 dana od utvrđene preliminarne pozitivnosti na ispitivane markere TTI. Kod ponovno pozitivnih uzoraka krvi rađen je potvrdni "Western Blot" test za određivanje antitela u humanom serumu ili plazmi, na markere TTI. Uzorci krvi pozitivni na potvrdnom testu na ispitivane markere TTI, prihvaćeni su kao potvrdno HBs Ag pozitivni, potvrdno anti-HCV reaktivni i potvrdno anti-HIV reaktivni. Rezultati Od ukupno testiranih trudnica bilo je 152 (1,27%) preliminarno reaktivnih, 38 potvrdno pozitivnih na HBsAg (0,32%) i 114 (0,95%) lažno reaktivnih na HBsAg; 123 (1,03%) preliminarno reaktivnih na anti-HCV, 35 potvrdno pozitivnih trudnica na antitelo antiHCV (0,29%) i 88 (0,74%) lažno pozitivnih na HCV; i 15 (0,13%) preliminarno reaktivnih, 5 trudnica potvrdno pozitivnih na antitelo anti-HIV (0,04%) i 10 (0,09%) lažno reaktivnih antiHIV. Od 934 testirane osobe sa rizičnim ponašanjem detektovano je 36 (3,85%) preliminarno reaktivnih na HBs Ag, 28 (2,99%) potvrdno pozitivnih na HbsAg i 8 (0,86%) lažno reaktivnih HBsAg; 38 (4,07%) preliminarno reaktivnih anti-HCV, 33 (3,53%) potvrdno pozitivnih na anti-HCV i 5 (0,54%) lažno reaktivnih na anti-HCV, kao i 10 (1,07%) preliminarno anti-HIV reaktivnih, 9 (0,96%) anti-HIV potvrdno pozitivnih i jedna (0,11%) osoba lažno-reaktivno na anti-HIV sa rizičnim ponašanjem. Zaključak Naše ispitivanje pokazuje veću prevalencu na HbsAg, anti-HCV i anti-HIV kod osoba sa rizičnim ponašanjem u odnosu na trudnice, ako i veću razliku u nalazu lažno reaktivnih rezultata kod trudnica, u odnosu na osobe rizičnog ponašanja. Preventivne mere sastojale bi se u edukaciji stanovništva o putevima širenja krvlju prenosivih bolesti, njihovoj prevenciji, testiranju krvi i krvnih produkata testovima najnovije generacije i pravilnom izvođenju medicinskih intervencija uz poštovanje principa asepse i antisepse

Uticaj vrste klona prokupca i postupka vinifikacije na sadržaj rezveratrola u vinu

The focus of this study was to investigate the effects of clones (subvarieties) of autochthonous Serbian grape variety Prokupac, along with the influence of vinification method on the content of transand cis-resveratrol as well as on total phenolic content (TPC) in wines. Wines were made from four clones of Prokupac variety (PR1, 40/1, PR6 and PR7) by application of different periods of maceration duration (1, 5 and 10 days). The effects of different species of selected wine yeasts and glucosidase enzymes on the quantity of resveratrol and TPC in wine made from PR6 variety were also investigated. The content of trans-resveratrol varied from 0.27 mg/L to 1.46 mg/L. The highest content of resveratrol was determined in Prokupac clone PR6, and the lowest in PR7 clone. An increase in resveratrol and TPC content was observed in all clones when the duration of maceration was prolonged. Wine produced by application of b enzyme preparation and 299 yeast had the highest concentration of total resveratrol (4.23 mg/L). The TPC was the highest in the wine made by combined application of yeast 299 and OE enzyme. The obtained results showed that by adequate selection of varieties, prolonged duration of maceration, application of appropriate species of yeast and enzyme preparations, it is possible to increase the content of resveratrol and other phenolic compounds in wine.Cilj ovog istraživanja bio je da se ispita uticaj različitih klonova autohtone srpske sorte Prokupac kao i postupak vinifikacije na sadržaj transi cisrezveratrola i sadržaj ukupnih polifenola (SUP) u vinima. Vina su proizvedena od četiri klona sorte Prokupac (PR1, 40/1, PR6 i PR7) primenom različitih dužina trajanja maceracije (1, 5 i 10 dana) za svaki klon. Takođe je ispitivan uticaj različitih izabranih kvasaca i enzimskih preparata glikozidaza na sadržaj rezveratrola i SUP u vinima proizvedenim od klona PR6. Sadržaj transi cisrezveratrola je određen HPLC metodom sa UV detektorom uz prethodnu tečno čvrstu ekstrakciju (SPE). Određivanje SUP je urađeno metodom po FolinČokalteu. Sadržaj transrezveratrola je bio od 0,27 mg/L do 1,46 mg/L. Najviši sadržaj rezveratrola je bio u klonu PR6 dok je najniži PR7. Povećanje sadržaja rezveratrola i SUP je primećeno kod svih klonova kada je maceracija duže trajala. Vino proizvedeno primenom enzimskog preparata glikozidaza b i kvasca 299 je imalo najviši sadržaj ukupnog rezvertrola (4,23 mg/L). Najviši SUP je bio u vinima proizvedenim primenom enzimskog preparata glikozidaza OE i kvasca 299. Dobijeni rezultati ukazuju da je izborom odgovarajućeg klona, dužine maceracije, primene odgovarajućeg kvasca i enzimskog preparata moguće povećati sadržaj rezveratrola i drugih fenolnih jedinjenja u vinu

Ispitivanje antiaritmijske aktivnosti novosintetisanih derivata propafenona u akonitinskom modelu srčane aritmije kod pacova

By applying of aconitictest in in vivo experiments in rats under deep anesthesia, there was investigated the antiarrhythmic potential of newly synthetized fluorinated derivatives of propafenone. The animals were divided into four experimental groups. The first (aconitine group) was treated with aconitine at a dose of 60 μg/kg, which led to pronounced cardiac rhythm disorder in a short period of time. The appearance of ventricular extrasystole (VES) was taken as a parameter for ascertainment of cardiac rhytm disorder. The remaining three animal groups were taken for testing the potential of propafenone and propafenone fluorinated derivatives to stop the arrhythmia, and which was induced by i.v. aconitine injection (60 μg/kg). Propafenone, as well as 50F derivative, did not convert the disturbed cardiac rhythm (survival of animals was 0%). By applying 5PF derivative in a dose of 6 mg/kg, the animals survived with occasional establishment of sinus rhythm.Primenom akonitinskog testa, u in vivo eksperimentima na pacovima u dubokoj anesteziji, ispitivan je antiaritmijski potencijal novosintetisanih fluoriranih derivata propafenona. Životinje su podeljene u četiri eksperimentalne grupe. Prva grupa (akonitinska grupa) je tretirana akonitinom u dozi od 60 μg/kg t.m., koja dovodi do vidnog poremećaja srčanog ritma u kratkom vremenskom periodu. Kao parameter za registrovanje poremećaja srčanog ritma uzetaje pojava ventrikularne ekstrasistole (VES). Ostale (tri) eksperimentalne grupe činile su životinje na kojima je ispitivan potencijal propafenona i fluoriranih derivata propafenona da zaustave aritmiju indukovanu i.v. injekcijom akonitina (60 μg/kg t.m.). Propafenon, kao i 50F derivat, nisu uspeli da konvertuju poremećen srčani ritam (preživljavanje životinja je 0 %). Prilikom aplikacije 5PF derivata u dozi od 6 mg/kg t.m. životinje su preživele, uz povremeno uspostavljanje sinusnog ritma

Relaksacija aorte pacova indukovana novosintetisanim orto-hlornim derivatom propafenona

The information on the inhibitory effect of propafenone in vascular smooth muscle is sparse. Propafenone acts through blockage of voltage-dependent cardiac Na+ channels, L-type Ca2+ channels, voltage-sensitive K+ (Kv) channels, as well as β-adrenergic receptors in the heart. The introduction of different chemical groups in the benzyl moiety of propafenone influences pharmacological properties of newly developed derivate of propafenone. Here we investigated the effect of new ortho-chloro derivate of propafenone (5OCl) on the vascular tone of precontracted rat aorta. 5OCl produced endothelium-independent relaxation of rat aorta. In order to test the involvement of different ion channels in 5OCl mechanism of action, antagonist of Na+, lidocaine, KV channels, 4-aminopyiridine (4-AP) and L-type Ca2+ channels, nifedipine were used. All tested antagonists of ion channels did not influence the relaxation of rat aorta induced by high a concentration of 5OCl (≥10 μM), but antagonized the relaxation induced by low concentrations of this propafenone derivate. Thus, 5OCl derivate has comparable potency and efficacy as propafenone. According to its interaction with lidocaine, 4-AP and nifedipine it seems that 5OCl partly shares the mechanism of action with propafenone. The mechanism of vasodilatation induced by high micromolar concentration of 5OCl is not defined and further investigations are necessary.Informacije o efektima propafenona na vaskularne glatke mišiće su oskudne. Propafenon blokira voltažno-zavisne Na+ kanale, Ca2+ kanale L-tipa, voltažno-senzitivne K+ (Kv) kanale i β-adrenergičke receptore u srcu. Uvođenje različitih hemijskih grupa u benzilni deo molekula propafenona utiče na promenu njegovih farmakoloških osobina. U ovoj studiji je ispitivan uticaj novog orto-hloro derivata (5OCl) propafenona na vaskularni tonus prekontrahovane aorte pacova. Orto hlorni derivat (5OCl) je izazvao endotel-nezavisnu relaksaciju aortnih prstenova. Da bi se ispitala uloga različitih jonskih kanala u ovoj relaksaciji, korišćeni su lidokain, (antagonist Na+ kanala), 4-aminopiridin (antagonist Kv kanala) i nifedipin (antagonist Ca2+ kanala L-tipa). Testirani antagonisti jonskih kanala nisu uticali na relaksaciju aorte pacova izazvanu visokom koncentracijom 5OCl (≥10 μM), ali su zato antagonizovali relaksaciju aorte koncentracijama 5OCl koje su bile manje od 10 μM. Prema tome, 5OCl derivat ima sličnu jačinu i efikasnost kao propafenon. Prema njegovoj interakciji sa lidokainom, 4-AP i nifedipinom može se reći da je mehanizam dejstva 5OCl sličan propafenonu. Mehanizam vazodilatacije 5OCl derivata u koncentracijama većim od 10 μM nije definisan i za to su potrebna dalja istraživanja