TY  - JOUR
AU  - Marinko, Marija
AU  - Novaković, Aleksandra
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4980
AB  - Hydrogen sulfide (H2 S) is the youngest member of the gasotransmitters family consisting
of nitric oxide (NO) and carbon monoxide (CO). This signalling molecule is implicated in the
regulation of a wide range of processes, such as inflammation, pain, and tissue repair, and has an
important role in signalling processes affecting cardiovascular health, either as an independent
effector or as an enhancer of the NO system.
With the discovery of the H2 S role in the pathogenesis of many diseases, the development
of new pharmaceuticals that could be useful in conditions with disturbed levels of endogenous
H2 S began. Today, the development of H2 S-releasing drugs has reached the level of clinical
studies. Drugs such as SG1002, aimed at the treatment of heart failure, and ATB-346, aimed at
the treatment of arthritis, have been tested in Phase I/II clinical studies and have shown significant
therapeutic potential. Additionally, it has been shown that some already known drugs, such as
zofenopril, produce part of their beneficial effects by releasing H2 S.
Evidence from clinical studies presented in this paper encourages further clinical testing of
H2 S-based therapeutics and the possibility of their application in a wide range of diseases, such
as hypertension, diabetes and chronic kidney disease.
AB  - Vodonik-sulfid (H2S) je najmlađi član porodice gasovitih medijatora koju čine azot-oksid
(NO) i ugljen-monoksid (CO). Ovaj signalni molekul uključen je u regulaciju širokog spektra
procesa, kao što su zapaljenje, bol, reparacija tkiva, i ima važnu ulogu u signalnim procesima koji
utiču na zdravlje kardiovaskularnog sistema, bilo kao nezavisni efektor ili kao pojačivač NO
signalnog puta.
Sa otkrivanjem uloge H 2 S-a u patogenezi mnogih bolesti, započeo je razvoj novih
farmaceutika koji bi mogli biti od koristi u stanjima sa poremećenim nivoima endogenog H2 S-a.
Razvoj lekova koji oslobađaju H2S danas je dosegao nivo kliničkih studija. Lekovi poput SG1002,
za terapiju srčane insuficijencije, i ATB-346, za terapiju artritisa, ispitivani su u Fazi I/II kliničkih
studija i pokazali značajan terapijski potencijal. Dodatno, pokazano je da neki već poznati lekovi,
poput zofenoprila, deo svojih korisnih efekata ostvaruju upravo oslobađanjem H 2 S-a.
Dokazi iz kliničkih studija izneti u ovom radu ohrabruju dalja klinička testiranja terapeutika
baziranih na H2 S-u i mogućnost njihove primene u širokom spektru bolesti, poput hipertenzije,
dijabetesa i hronične bolesti bubrega.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
T2  - Arhiv za farmaciju
T1  - Hydrogen sulfide-releasing therapeutics - how far have we come in clinical studies?
T1  - Lekovi koji oslobađaju vodonik-sulfid – dokle smo stigli u kliničkim studijama?
VL  - 73
IS  - 3
SP  - 173
EP  - 189
DO  - 10.5937/arhfarm73-44691
ER  - 

@article{
author = "Marinko, Marija and Novaković, Aleksandra",
year = "2023",
abstract = "Hydrogen sulfide (H2 S) is the youngest member of the gasotransmitters family consisting
of nitric oxide (NO) and carbon monoxide (CO). This signalling molecule is implicated in the
regulation of a wide range of processes, such as inflammation, pain, and tissue repair, and has an
important role in signalling processes affecting cardiovascular health, either as an independent
effector or as an enhancer of the NO system.
With the discovery of the H2 S role in the pathogenesis of many diseases, the development
of new pharmaceuticals that could be useful in conditions with disturbed levels of endogenous
H2 S began. Today, the development of H2 S-releasing drugs has reached the level of clinical
studies. Drugs such as SG1002, aimed at the treatment of heart failure, and ATB-346, aimed at
the treatment of arthritis, have been tested in Phase I/II clinical studies and have shown significant
therapeutic potential. Additionally, it has been shown that some already known drugs, such as
zofenopril, produce part of their beneficial effects by releasing H2 S.
Evidence from clinical studies presented in this paper encourages further clinical testing of
H2 S-based therapeutics and the possibility of their application in a wide range of diseases, such
as hypertension, diabetes and chronic kidney disease., Vodonik-sulfid (H2S) je najmlađi član porodice gasovitih medijatora koju čine azot-oksid
(NO) i ugljen-monoksid (CO). Ovaj signalni molekul uključen je u regulaciju širokog spektra
procesa, kao što su zapaljenje, bol, reparacija tkiva, i ima važnu ulogu u signalnim procesima koji
utiču na zdravlje kardiovaskularnog sistema, bilo kao nezavisni efektor ili kao pojačivač NO
signalnog puta.
Sa otkrivanjem uloge H 2 S-a u patogenezi mnogih bolesti, započeo je razvoj novih
farmaceutika koji bi mogli biti od koristi u stanjima sa poremećenim nivoima endogenog H2 S-a.
Razvoj lekova koji oslobađaju H2S danas je dosegao nivo kliničkih studija. Lekovi poput SG1002,
za terapiju srčane insuficijencije, i ATB-346, za terapiju artritisa, ispitivani su u Fazi I/II kliničkih
studija i pokazali značajan terapijski potencijal. Dodatno, pokazano je da neki već poznati lekovi,
poput zofenoprila, deo svojih korisnih efekata ostvaruju upravo oslobađanjem H 2 S-a.
Dokazi iz kliničkih studija izneti u ovom radu ohrabruju dalja klinička testiranja terapeutika
baziranih na H2 S-u i mogućnost njihove primene u širokom spektru bolesti, poput hipertenzije,
dijabetesa i hronične bolesti bubrega.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Hydrogen sulfide-releasing therapeutics - how far have we come in clinical studies?, Lekovi koji oslobađaju vodonik-sulfid – dokle smo stigli u kliničkim studijama?",
volume = "73",
number = "3",
pages = "173-189",
doi = "10.5937/arhfarm73-44691"
}

Marinko, M.,& Novaković, A.. (2023). Hydrogen sulfide-releasing therapeutics - how far have we come in clinical studies?. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 73(3), 173-189.
https://doi.org/10.5937/arhfarm73-44691

Marinko M, Novaković A. Hydrogen sulfide-releasing therapeutics - how far have we come in clinical studies?. in Arhiv za farmaciju. 2023;73(3):173-189.
doi:10.5937/arhfarm73-44691 .

Marinko, Marija, Novaković, Aleksandra, "Hydrogen sulfide-releasing therapeutics - how far have we come in clinical studies?" in Arhiv za farmaciju, 73, no. 3 (2023):173-189,
https://doi.org/10.5937/arhfarm73-44691 . .

TY  - CONF
AU  - Marinko, Marija
AU  - Janković, Goran
AU  - Milojević, Predrag
AU  - Stojanović, Ivan
AU  - Nenezić, Dragoslav
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
AU  - Novaković, Aleksandra
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4492
AB  - Findings from epidemiological studies indicate that polyphenols, widespread in
human diet and with numerous biological activities, act cardioprotectively. Procyanidins are
subclass of polyphenols with high content in commonly consumed foods and beverages, such
as grapes, tea, chocolate, nuts and apples. Cardioprotective abilities of procyanidins, might, at
least partly, attribute to their vasodilator properties. Since exact mechanisms of procyanidin
B2-induced vasorelaxation are unknown, our study aimed to investigate relaxant effect of
procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms.
Discarded segments of HSV were collected from patients undergoing bypass surgery and
studied in organ baths. Procyanidin B2 caused concentration-dependent relaxation of HSV
precontracted by phenylephrine. The relaxation was strongly affected by inhibitors of
NO/cGMP pathway, L-NAME, hydroxocobalamin and ODQ. Indomethacin, a cyclooxygenase
inhibitor, significantly reduced only relaxation produced by the highest concentrations of
procyanidin B2. Combination of apamin and TRAM-34, selective blockers of small- and
intermediate-conductance Ca 2+ -activated K+ (KCa ) channels (SKCa and IK Ca ), in the presence of
L-NAME and indomethacin, did not additionally affect procyanidin B2-induced relaxation.
Additionally, relaxation induced by procyanidin B2 was partially attenuated by 4-
aminopyridine, predominant blocker of voltage-gated K+ (KV) channels, significantly
inhibited by glibenclamide, selective ATP-sensitive K+ (KATP) channels inhibitor, and almost
abolished by iberiotoxin, highly selective blocker of large-conductance KCa (BKCa ). Our results
revealed that procyanidin B2 acts as a potent vasodilator on isolated human venous graft.
Mechanism of this relaxation of HSV probably involves stimulation of NO production, as well
K+ channels opening, especially BK Ca , and partially KATP and KV
AB  - Nalazi epidemioloških studija ukazuju da polifenoli, široko rasprostranjeni u ljudskoj
ishrani i sa brojnim biološkim aktivnostima, deluju kardioprotektivno. Procijanidini su
podklasa polifenola sa visokim sadržajem u često konzumiranoj hrani i pićima, kao što su
grožđe, čaj, čokolada, orašasti plodovi i jabuke. Kardioprotektivno delovanje procijanidina
može se, bar delimično, pripisati njihovim vazodilatatornim svojstvima. S obzirom da tačni
mehanizmi pomoću kojih procijanidin B2 izaziva vazorelaksaciju nisu poznati, cilj naše
studije bio je da istražimo relaksantni efekat procijanidina B2 na izolovanoj humanoj veni
safeni (HSV) i njegove osnovne mehanizme.Neiskorišćeni segmenti HSV su uzimani od
pacijenata u toku bajpas operacija i ispitivani u kupatilu za izolovane organe. Procijanidin B2
izazvao je koncentracijski-zavisnu relaksaciju HSV prekontrahovane fenilefrinom. Na
relaksaciju su snažno uticali inhibitori NO/cGMP puta, L-NAME, hidroksokobalamin i ODQ.
Indometacin, inhibitor ciklooksigenaze, značajno je umanjio samo relaksaciju izazivanu
najvećim koncentracijama procijanidina B2. Kombinacija apamina i TRAM-34, selektivnih
blokatora Ca 2+ -zavisnih K+ (KCa ) kanala male i srednje provodljivosti (SKCa i IK Ca ), u prisustvu
L-NAME i indometacina, nije dodatno uticala na relaksaciju uzrokovanu procijanidinom B2.
Osim toga, procijanidinom B2 izazvana relaksacija bila je delimično umanjena 4-
aminopiridinom, dominantnim blokatorom voltažno-zavisnih K+ (KV) kanala, značajno
inhibirana glibenklamidom, selektivnim inhibitorom ATP-zavisnih K+ (KATP) kanala, i skoro
potpuno blokirana iberiotoksinom, selektivnim blokatorom K Ca velike provodljivosti (BK Ca).
Naši rezultati pokazuju da procijanidin B2 deluje kao moćni vazodilatator na izolovanom
humanom venskom graftu. Mehanizam ove relaksacije HSV verovatno uključuje stimulaciju
proizvodnje NO, kao i otvaranje K+ kanala, posebno BK Ca , i delimično KATP i KV
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Mechanism underlying vasorelaxation of human saphenous vein induced by procyanidin B2
T1  - Mehanizam vazorelaksacije humane vene safene izazvane procijanidinom B2
VL  - 72
IS  - 4 suplement
SP  - S190
EP  - S191
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4492
ER  - 

@conference{
author = "Marinko, Marija and Janković, Goran and Milojević, Predrag and Stojanović, Ivan and Nenezić, Dragoslav and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei and Novaković, Aleksandra",
year = "2022",
abstract = "Findings from epidemiological studies indicate that polyphenols, widespread in
human diet and with numerous biological activities, act cardioprotectively. Procyanidins are
subclass of polyphenols with high content in commonly consumed foods and beverages, such
as grapes, tea, chocolate, nuts and apples. Cardioprotective abilities of procyanidins, might, at
least partly, attribute to their vasodilator properties. Since exact mechanisms of procyanidin
B2-induced vasorelaxation are unknown, our study aimed to investigate relaxant effect of
procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms.
Discarded segments of HSV were collected from patients undergoing bypass surgery and
studied in organ baths. Procyanidin B2 caused concentration-dependent relaxation of HSV
precontracted by phenylephrine. The relaxation was strongly affected by inhibitors of
NO/cGMP pathway, L-NAME, hydroxocobalamin and ODQ. Indomethacin, a cyclooxygenase
inhibitor, significantly reduced only relaxation produced by the highest concentrations of
procyanidin B2. Combination of apamin and TRAM-34, selective blockers of small- and
intermediate-conductance Ca 2+ -activated K+ (KCa ) channels (SKCa and IK Ca ), in the presence of
L-NAME and indomethacin, did not additionally affect procyanidin B2-induced relaxation.
Additionally, relaxation induced by procyanidin B2 was partially attenuated by 4-
aminopyridine, predominant blocker of voltage-gated K+ (KV) channels, significantly
inhibited by glibenclamide, selective ATP-sensitive K+ (KATP) channels inhibitor, and almost
abolished by iberiotoxin, highly selective blocker of large-conductance KCa (BKCa ). Our results
revealed that procyanidin B2 acts as a potent vasodilator on isolated human venous graft.
Mechanism of this relaxation of HSV probably involves stimulation of NO production, as well
K+ channels opening, especially BK Ca , and partially KATP and KV, Nalazi epidemioloških studija ukazuju da polifenoli, široko rasprostranjeni u ljudskoj
ishrani i sa brojnim biološkim aktivnostima, deluju kardioprotektivno. Procijanidini su
podklasa polifenola sa visokim sadržajem u često konzumiranoj hrani i pićima, kao što su
grožđe, čaj, čokolada, orašasti plodovi i jabuke. Kardioprotektivno delovanje procijanidina
može se, bar delimično, pripisati njihovim vazodilatatornim svojstvima. S obzirom da tačni
mehanizmi pomoću kojih procijanidin B2 izaziva vazorelaksaciju nisu poznati, cilj naše
studije bio je da istražimo relaksantni efekat procijanidina B2 na izolovanoj humanoj veni
safeni (HSV) i njegove osnovne mehanizme.Neiskorišćeni segmenti HSV su uzimani od
pacijenata u toku bajpas operacija i ispitivani u kupatilu za izolovane organe. Procijanidin B2
izazvao je koncentracijski-zavisnu relaksaciju HSV prekontrahovane fenilefrinom. Na
relaksaciju su snažno uticali inhibitori NO/cGMP puta, L-NAME, hidroksokobalamin i ODQ.
Indometacin, inhibitor ciklooksigenaze, značajno je umanjio samo relaksaciju izazivanu
najvećim koncentracijama procijanidina B2. Kombinacija apamina i TRAM-34, selektivnih
blokatora Ca 2+ -zavisnih K+ (KCa ) kanala male i srednje provodljivosti (SKCa i IK Ca ), u prisustvu
L-NAME i indometacina, nije dodatno uticala na relaksaciju uzrokovanu procijanidinom B2.
Osim toga, procijanidinom B2 izazvana relaksacija bila je delimično umanjena 4-
aminopiridinom, dominantnim blokatorom voltažno-zavisnih K+ (KV) kanala, značajno
inhibirana glibenklamidom, selektivnim inhibitorom ATP-zavisnih K+ (KATP) kanala, i skoro
potpuno blokirana iberiotoksinom, selektivnim blokatorom K Ca velike provodljivosti (BK Ca).
Naši rezultati pokazuju da procijanidin B2 deluje kao moćni vazodilatator na izolovanom
humanom venskom graftu. Mehanizam ove relaksacije HSV verovatno uključuje stimulaciju
proizvodnje NO, kao i otvaranje K+ kanala, posebno BK Ca , i delimično KATP i KV",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Mechanism underlying vasorelaxation of human saphenous vein induced by procyanidin B2, Mehanizam vazorelaksacije humane vene safene izazvane procijanidinom B2",
volume = "72",
number = "4 suplement",
pages = "S190-S191",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4492"
}

Marinko, M., Janković, G., Milojević, P., Stojanović, I., Nenezić, D., Kanjuh, V., Yang, Q., He, G.,& Novaković, A.. (2022). Mechanism underlying vasorelaxation of human saphenous vein induced by procyanidin B2. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S190-S191.
https://hdl.handle.net/21.15107/rcub_farfar_4492

Marinko M, Janković G, Milojević P, Stojanović I, Nenezić D, Kanjuh V, Yang Q, He G, Novaković A. Mechanism underlying vasorelaxation of human saphenous vein induced by procyanidin B2. in Arhiv za farmaciju. 2022;72(4 suplement):S190-S191.
https://hdl.handle.net/21.15107/rcub_farfar_4492 .

Marinko, Marija, Janković, Goran, Milojević, Predrag, Stojanović, Ivan, Nenezić, Dragoslav, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, Novaković, Aleksandra, "Mechanism underlying vasorelaxation of human saphenous vein induced by procyanidin B2" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S190-S191,
https://hdl.handle.net/21.15107/rcub_farfar_4492 .

TY  - JOUR
AU  - Marinko, Marija
AU  - Hou, Hai-Tao
AU  - Stojanović, Ivan
AU  - Milojević, Predrag
AU  - Nenezić, Dragoslav
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
AU  - Novaković, Aleksandra
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3901
AB  - Hydrogen sulfide (H2S) represents the third and the youngest member of the gaseous transmitters family. The dominant effect of H2S on isolated vessels is vasodilation. As the mechanism of H2S-induced relaxation in human vessels remains unclear, the present study aimed to investigate the effects of H2S donor, sodium hydrosulfide (NaHS), on isolated human saphenous vein (HSV) and to determine the mechanism of action. Our results showed that NaHS (1 µM–3 mM) induced a concentration-dependent relaxation of endothelium-intact HSV rings pre-contracted by phenylephrine. Pre-treatment with L-NAME, ODQ and KT5823 significantly inhibited NaHS-induced relaxation, while indomethacin induced partial inhibition. Among K+ channel blockers, the combination of apamin and TRAM-34 significantly affected the relaxation produced by NaHS, while iberiotoxin and glibenclamide only reduced maximal relaxation of HSV. NaHS partially relaxed endothelium-intact rings pre-contracted by high K+, as well as phenylephrine-contracted rings in the presence of nifedipine. Additionally, the incubation of HSV rings with NaHS increased NO production. These results demonstrate that NaHS produces the concentration- and endothelium-dependent relaxation of isolated HSV. Vasorelaxation to NaHS probably involves activation of NO/cGMP/PKG pathway and partially prostacyclin. In addition, different K+ channels subtypes, especially SKCa and IKCa, as well as BKCa and KATP channels in high concentrations of NaHS, probably participate in the NaHS-induced vasorelaxation.
PB  - Blackwell Publishing Ltd
T2  - Fundamental and Clinical Pharmacology
T1  - Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein
VL  - 35
IS  - 5
SP  - 906
EP  - 918
DO  - 10.1111/fcp.12658
ER  - 

@article{
author = "Marinko, Marija and Hou, Hai-Tao and Stojanović, Ivan and Milojević, Predrag and Nenezić, Dragoslav and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei and Novaković, Aleksandra",
year = "2021",
abstract = "Hydrogen sulfide (H2S) represents the third and the youngest member of the gaseous transmitters family. The dominant effect of H2S on isolated vessels is vasodilation. As the mechanism of H2S-induced relaxation in human vessels remains unclear, the present study aimed to investigate the effects of H2S donor, sodium hydrosulfide (NaHS), on isolated human saphenous vein (HSV) and to determine the mechanism of action. Our results showed that NaHS (1 µM–3 mM) induced a concentration-dependent relaxation of endothelium-intact HSV rings pre-contracted by phenylephrine. Pre-treatment with L-NAME, ODQ and KT5823 significantly inhibited NaHS-induced relaxation, while indomethacin induced partial inhibition. Among K+ channel blockers, the combination of apamin and TRAM-34 significantly affected the relaxation produced by NaHS, while iberiotoxin and glibenclamide only reduced maximal relaxation of HSV. NaHS partially relaxed endothelium-intact rings pre-contracted by high K+, as well as phenylephrine-contracted rings in the presence of nifedipine. Additionally, the incubation of HSV rings with NaHS increased NO production. These results demonstrate that NaHS produces the concentration- and endothelium-dependent relaxation of isolated HSV. Vasorelaxation to NaHS probably involves activation of NO/cGMP/PKG pathway and partially prostacyclin. In addition, different K+ channels subtypes, especially SKCa and IKCa, as well as BKCa and KATP channels in high concentrations of NaHS, probably participate in the NaHS-induced vasorelaxation.",
publisher = "Blackwell Publishing Ltd",
journal = "Fundamental and Clinical Pharmacology",
title = "Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein",
volume = "35",
number = "5",
pages = "906-918",
doi = "10.1111/fcp.12658"
}

Marinko, M., Hou, H., Stojanović, I., Milojević, P., Nenezić, D., Kanjuh, V., Yang, Q., He, G.,& Novaković, A.. (2021). Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein. in Fundamental and Clinical Pharmacology
Blackwell Publishing Ltd., 35(5), 906-918.
https://doi.org/10.1111/fcp.12658

Marinko M, Hou H, Stojanović I, Milojević P, Nenezić D, Kanjuh V, Yang Q, He G, Novaković A. Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein. in Fundamental and Clinical Pharmacology. 2021;35(5):906-918.
doi:10.1111/fcp.12658 .

Marinko, Marija, Hou, Hai-Tao, Stojanović, Ivan, Milojević, Predrag, Nenezić, Dragoslav, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, Novaković, Aleksandra, "Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein" in Fundamental and Clinical Pharmacology, 35, no. 5 (2021):906-918,
https://doi.org/10.1111/fcp.12658 . .

TY  - THES
AU  - Marinko, Marija
PY  - 2020
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7753
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:22987/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=23129865
UR  - https://nardus.mpn.gov.rs/handle/123456789/17654
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3755
AB  - Gasotransmiteri ostvaruju deo svojih uticaja na organizam regulacijom jonskih kanala, posebno kalijumovih (K+) kanala. Promenjena struktura/funkcija jonskih kanala, ali i poremećaji metabolizma i/ili nivoa gasotransmitera, povezani su sa nekoliko patofizioloških stanja, uključujući kardiovaskularne bolesti.Glavni cilj našeg istraživanja bio je ispitivanje mehanizama vazodilatatornog dejstva nikorandila, donora azot monoksida (NO), i natrijum-hidrogensulfida, donora vodonik-sulfida (H2S), na izolovanoj unutrašnjoj torakalnoj arteriji i veni safeni čoveka.Neiskorišćeni segmenti unutrašnje torakalne arterije i vene safene uzimani su od pacijenata tokom bajpas operacija. Ispitivanje je rađeno u in vitro uslovima u sistemu za izolovane organe. Koncentracijski-zavisne krive relaksacije konstruisane su na prekontrahovanim preparatima sa i bez endotela u prisustvu/odsustvu blokatora K+ kanala i/ili inhibitora signalnog puta cikličnog gvanozin-monofosfata (cGMP).Naši rezultati su pokazali da nikorandil i natrijum-hidrogensulfid prouzrokuju koncentracijski-zavisnu relaksaciju izolovane humane vene safene i unutrašnje torakalne arterije prekontrahovane fenilefrinom. Nikorandil izaziva endotel-nezavisnu, a natrijum-hidrogensulfid endotel-zavisnu relaksaciju oba krvna suda. Signalni put cGMP-a ima značajnu ulogu u vazorelaksantnom efektu nikorandila. Takođe, mehanizam dejstva natrijum-hidrogensulfida uključuje pojačanje NO/cGMP signalnog puta na oba krvna suda. Kalijumovi kanali doprinose relaksantnom dejstvu oba ispitivana agensa, s tim da postoje razlike u tipovima K+ kanala i njihovom relativnom značaju.S obzirom da se spazam vene safene i unutrašnje torakalne arterije i dalje javlja u kliničkim uslovima, a njegova prevencija i reverzija još uvek predstavljaju izazov, rezultati naše studije mogu ukazati na nove tarapijske ciljeve u lečenju spazma bajpas graftova i potencijalno dati farmakološku osnovu za razvoj novih vazodilatatornih lekova.
AB  - Gasotransmitters exert part of their impact on the organism via regulation of ion channels, especially potassium (K+) channels. Altered structure/function of ion channels, as well disorders of the metabolism and/or levels of the gasotransmitters are associated with several pathophysiological conditions, including cardiovascular diseases.The principal aim of our study was to investigate the mechanisms of vasodilator action of nicorandil, a nitric oxide (NO) donor, and of sodium hydrosulfide, a hydrogen sulfide (H2S) donor, on the isolated human internal thoracic artery and saphenous vein.Discarded segments of the internal thoracic artery and saphenous vein were collected from patients undergoing coronary artery bypass grafting. The investigation was performed in vitro in an isolated organs system. Concentration-response curves were constructed on pre-contracted preparations with and without endothelium in the presence/absence of K+ channel blockers and/or cyclic guanosine monophosphate (cGMP) pathway inhibitors.Our results showed that nicorandil and sodium hydrosulfide cause a concentration-dependent relaxation of the isolated human saphenous vein and internal thoracic artery pre-contracted by phenylephrine. Nicorandil exerts endothelium-independent and sodium hydrosulfide endothelium-dependent relaxation of both blood vessels. cGMP signalling pathway plays a significant role in the vasorelaxant effect of nicorandil. Also, sodium hydrosulfide mechanism of action involves enhancement of the NO/cGMP signalling pathway in both vessels. Potassium channels contribute to the relaxant effect of both investigated agents, although differences exist in K+ channel subtypes and their relative importance.Since the spasm of saphenous vein and internal thoracic artery still occurs in clinical settings, and its prevention and reversion is still challenging, the results of our study may indicate new targets in the treatment of bypass grafts spasm, and potentially provide a pharmacological basis for the development of new vasodilator drugs.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Vazodilatatorno delovanje donora azot monoksida i vodonik-sulfida na izolovanoj unutrašnjoj torakalnoj arteriji i veni safeni čoveka: uloga kalijumovih kanala
UR  - https://hdl.handle.net/21.15107/rcub_nardus_17654
ER  - 

@phdthesis{
author = "Marinko, Marija",
year = "2020",
abstract = "Gasotransmiteri ostvaruju deo svojih uticaja na organizam regulacijom jonskih kanala, posebno kalijumovih (K+) kanala. Promenjena struktura/funkcija jonskih kanala, ali i poremećaji metabolizma i/ili nivoa gasotransmitera, povezani su sa nekoliko patofizioloških stanja, uključujući kardiovaskularne bolesti.Glavni cilj našeg istraživanja bio je ispitivanje mehanizama vazodilatatornog dejstva nikorandila, donora azot monoksida (NO), i natrijum-hidrogensulfida, donora vodonik-sulfida (H2S), na izolovanoj unutrašnjoj torakalnoj arteriji i veni safeni čoveka.Neiskorišćeni segmenti unutrašnje torakalne arterije i vene safene uzimani su od pacijenata tokom bajpas operacija. Ispitivanje je rađeno u in vitro uslovima u sistemu za izolovane organe. Koncentracijski-zavisne krive relaksacije konstruisane su na prekontrahovanim preparatima sa i bez endotela u prisustvu/odsustvu blokatora K+ kanala i/ili inhibitora signalnog puta cikličnog gvanozin-monofosfata (cGMP).Naši rezultati su pokazali da nikorandil i natrijum-hidrogensulfid prouzrokuju koncentracijski-zavisnu relaksaciju izolovane humane vene safene i unutrašnje torakalne arterije prekontrahovane fenilefrinom. Nikorandil izaziva endotel-nezavisnu, a natrijum-hidrogensulfid endotel-zavisnu relaksaciju oba krvna suda. Signalni put cGMP-a ima značajnu ulogu u vazorelaksantnom efektu nikorandila. Takođe, mehanizam dejstva natrijum-hidrogensulfida uključuje pojačanje NO/cGMP signalnog puta na oba krvna suda. Kalijumovi kanali doprinose relaksantnom dejstvu oba ispitivana agensa, s tim da postoje razlike u tipovima K+ kanala i njihovom relativnom značaju.S obzirom da se spazam vene safene i unutrašnje torakalne arterije i dalje javlja u kliničkim uslovima, a njegova prevencija i reverzija još uvek predstavljaju izazov, rezultati naše studije mogu ukazati na nove tarapijske ciljeve u lečenju spazma bajpas graftova i potencijalno dati farmakološku osnovu za razvoj novih vazodilatatornih lekova., Gasotransmitters exert part of their impact on the organism via regulation of ion channels, especially potassium (K+) channels. Altered structure/function of ion channels, as well disorders of the metabolism and/or levels of the gasotransmitters are associated with several pathophysiological conditions, including cardiovascular diseases.The principal aim of our study was to investigate the mechanisms of vasodilator action of nicorandil, a nitric oxide (NO) donor, and of sodium hydrosulfide, a hydrogen sulfide (H2S) donor, on the isolated human internal thoracic artery and saphenous vein.Discarded segments of the internal thoracic artery and saphenous vein were collected from patients undergoing coronary artery bypass grafting. The investigation was performed in vitro in an isolated organs system. Concentration-response curves were constructed on pre-contracted preparations with and without endothelium in the presence/absence of K+ channel blockers and/or cyclic guanosine monophosphate (cGMP) pathway inhibitors.Our results showed that nicorandil and sodium hydrosulfide cause a concentration-dependent relaxation of the isolated human saphenous vein and internal thoracic artery pre-contracted by phenylephrine. Nicorandil exerts endothelium-independent and sodium hydrosulfide endothelium-dependent relaxation of both blood vessels. cGMP signalling pathway plays a significant role in the vasorelaxant effect of nicorandil. Also, sodium hydrosulfide mechanism of action involves enhancement of the NO/cGMP signalling pathway in both vessels. Potassium channels contribute to the relaxant effect of both investigated agents, although differences exist in K+ channel subtypes and their relative importance.Since the spasm of saphenous vein and internal thoracic artery still occurs in clinical settings, and its prevention and reversion is still challenging, the results of our study may indicate new targets in the treatment of bypass grafts spasm, and potentially provide a pharmacological basis for the development of new vasodilator drugs.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Vazodilatatorno delovanje donora azot monoksida i vodonik-sulfida na izolovanoj unutrašnjoj torakalnoj arteriji i veni safeni čoveka: uloga kalijumovih kanala",
url = "https://hdl.handle.net/21.15107/rcub_nardus_17654"
}

Marinko, M.. (2020). Vazodilatatorno delovanje donora azot monoksida i vodonik-sulfida na izolovanoj unutrašnjoj torakalnoj arteriji i veni safeni čoveka: uloga kalijumovih kanala. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_17654

Marinko M. Vazodilatatorno delovanje donora azot monoksida i vodonik-sulfida na izolovanoj unutrašnjoj torakalnoj arteriji i veni safeni čoveka: uloga kalijumovih kanala. in Универзитет у Београду. 2020;.
https://hdl.handle.net/21.15107/rcub_nardus_17654 .

Marinko, Marija, "Vazodilatatorno delovanje donora azot monoksida i vodonik-sulfida na izolovanoj unutrašnjoj torakalnoj arteriji i veni safeni čoveka: uloga kalijumovih kanala" in Универзитет у Београду (2020),
https://hdl.handle.net/21.15107/rcub_nardus_17654 .

TY  - CONF
AU  - Novaković, Aleksandra
AU  - Marinko, Marija
AU  - Janković, Goran
AU  - Stojanović, Ivan
AU  - Milojević, Predrag
AU  - Nenezić, Dragoslav
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3260
PB  - Springer
C3  - European Journal of Clinical Pharmacology
T1  - Vasorelaxation of human saphenous vein induced by epicatechin
VL  - 75, Suppl. 1
SP  - S24
EP  - S24
DO  - 10.1007/s00228-019-02685-2
ER  - 

@conference{
author = "Novaković, Aleksandra and Marinko, Marija and Janković, Goran and Stojanović, Ivan and Milojević, Predrag and Nenezić, Dragoslav and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei",
year = "2019",
publisher = "Springer",
journal = "European Journal of Clinical Pharmacology",
title = "Vasorelaxation of human saphenous vein induced by epicatechin",
volume = "75, Suppl. 1",
pages = "S24-S24",
doi = "10.1007/s00228-019-02685-2"
}

Novaković, A., Marinko, M., Janković, G., Stojanović, I., Milojević, P., Nenezić, D., Kanjuh, V., Yang, Q.,& He, G.. (2019). Vasorelaxation of human saphenous vein induced by epicatechin. in European Journal of Clinical Pharmacology
Springer., 75, Suppl. 1, S24-S24.
https://doi.org/10.1007/s00228-019-02685-2

Novaković A, Marinko M, Janković G, Stojanović I, Milojević P, Nenezić D, Kanjuh V, Yang Q, He G. Vasorelaxation of human saphenous vein induced by epicatechin. in European Journal of Clinical Pharmacology. 2019;75, Suppl. 1:S24-S24.
doi:10.1007/s00228-019-02685-2 .

Novaković, Aleksandra, Marinko, Marija, Janković, Goran, Stojanović, Ivan, Milojević, Predrag, Nenezić, Dragoslav, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, "Vasorelaxation of human saphenous vein induced by epicatechin" in European Journal of Clinical Pharmacology, 75, Suppl. 1 (2019):S24-S24,
https://doi.org/10.1007/s00228-019-02685-2 . .

TY  - JOUR
AU  - Janković, Goran
AU  - Marinko, Marija
AU  - Milojević, Predrag
AU  - Stojanović, Ivan
AU  - Nenezić, Dragoslav
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
AU  - Novaković, Aleksandra
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3515
AB  - Cardioprotective abilities of procyanidins, might, at least in part, attribute to their vasodilator properties. The present study was undertaken to assess the vasorelaxant effect of procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms. Procyanidin B2 relaxed phenylephrine-induced contraction of HSV rings in concentration-dependent manner. The relaxation was dependent on the presence of endothelium and was strongly affected by l-NAME, hydroxocobalamin or ODQ, the inhibitors of NO/cGMP pathway. Indomethacin significantly affected only the relaxation produced by the highest concentrations of procyanidin B2. Apamin and TRAM-34 combination, in the presence of l-NAME and indomethacin, did not additionally decreased procyanidin B2-induced relaxation. In the presence of K+ channel blockers, relaxation induced by procyanidin B2 was partially attenuated by 4-aminopyridine, significantly inhibited by glibenclamide and almost abolished by iberiotoxin. Procyanidin B2 also relaxed the contractions induced by phenylephrine or caffeine in Ca2+-free solution. Finally, nifedipine slightly, while thapsigargin strongly antagonized HSV relaxation. Our results indicate that procyanidin B2 induces endothelium-dependent relaxation of HSV, which results primarily from stimulation of NO production, as well K+ channels opening, especially BKCa, and partially KATP and KV. Regulation of the intracellular Ca2+ release and inhibition of Ca2+ influx probably contr
PB  - Elsevier B.V.
T2  - Journal of Pharmacological Sciences
T1  - Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft
VL  - 142
IS  - 3
SP  - 101
EP  - 108
DO  - 10.1016/j.jphs.2019.11.006
ER  - 

@article{
author = "Janković, Goran and Marinko, Marija and Milojević, Predrag and Stojanović, Ivan and Nenezić, Dragoslav and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei and Novaković, Aleksandra",
year = "2019",
abstract = "Cardioprotective abilities of procyanidins, might, at least in part, attribute to their vasodilator properties. The present study was undertaken to assess the vasorelaxant effect of procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms. Procyanidin B2 relaxed phenylephrine-induced contraction of HSV rings in concentration-dependent manner. The relaxation was dependent on the presence of endothelium and was strongly affected by l-NAME, hydroxocobalamin or ODQ, the inhibitors of NO/cGMP pathway. Indomethacin significantly affected only the relaxation produced by the highest concentrations of procyanidin B2. Apamin and TRAM-34 combination, in the presence of l-NAME and indomethacin, did not additionally decreased procyanidin B2-induced relaxation. In the presence of K+ channel blockers, relaxation induced by procyanidin B2 was partially attenuated by 4-aminopyridine, significantly inhibited by glibenclamide and almost abolished by iberiotoxin. Procyanidin B2 also relaxed the contractions induced by phenylephrine or caffeine in Ca2+-free solution. Finally, nifedipine slightly, while thapsigargin strongly antagonized HSV relaxation. Our results indicate that procyanidin B2 induces endothelium-dependent relaxation of HSV, which results primarily from stimulation of NO production, as well K+ channels opening, especially BKCa, and partially KATP and KV. Regulation of the intracellular Ca2+ release and inhibition of Ca2+ influx probably contr",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmacological Sciences",
title = "Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft",
volume = "142",
number = "3",
pages = "101-108",
doi = "10.1016/j.jphs.2019.11.006"
}

Janković, G., Marinko, M., Milojević, P., Stojanović, I., Nenezić, D., Kanjuh, V., Yang, Q., He, G.,& Novaković, A.. (2019). Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft. in Journal of Pharmacological Sciences
Elsevier B.V.., 142(3), 101-108.
https://doi.org/10.1016/j.jphs.2019.11.006

Janković G, Marinko M, Milojević P, Stojanović I, Nenezić D, Kanjuh V, Yang Q, He G, Novaković A. Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft. in Journal of Pharmacological Sciences. 2019;142(3):101-108.
doi:10.1016/j.jphs.2019.11.006 .

Janković, Goran, Marinko, Marija, Milojević, Predrag, Stojanović, Ivan, Nenezić, Dragoslav, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, Novaković, Aleksandra, "Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft" in Journal of Pharmacological Sciences, 142, no. 3 (2019):101-108,
https://doi.org/10.1016/j.jphs.2019.11.006 . .

TY  - CONF
AU  - Novaković, Aleksandra
AU  - Marinko, Marija
AU  - Janković, Goran
AU  - Nenezić, Dragoslav
AU  - Stojanović, Ivan
AU  - Milojević, Predrag
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3072
PB  - Elsevier Ireland Ltd, Clare
C3  - Atherosclerosis
T1  - Cardioprotective effect of procyanidin B2
VL  - 275
SP  - e72
EP  - e72
DO  - 10.1016/j.atherosclerosis.2018.06.200
ER  - 

@conference{
author = "Novaković, Aleksandra and Marinko, Marija and Janković, Goran and Nenezić, Dragoslav and Stojanović, Ivan and Milojević, Predrag and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei",
year = "2018",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Atherosclerosis",
title = "Cardioprotective effect of procyanidin B2",
volume = "275",
pages = "e72-e72",
doi = "10.1016/j.atherosclerosis.2018.06.200"
}

Novaković, A., Marinko, M., Janković, G., Nenezić, D., Stojanović, I., Milojević, P., Kanjuh, V., Yang, Q.,& He, G.. (2018). Cardioprotective effect of procyanidin B2. in Atherosclerosis
Elsevier Ireland Ltd, Clare., 275, e72-e72.
https://doi.org/10.1016/j.atherosclerosis.2018.06.200

Novaković A, Marinko M, Janković G, Nenezić D, Stojanović I, Milojević P, Kanjuh V, Yang Q, He G. Cardioprotective effect of procyanidin B2. in Atherosclerosis. 2018;275:e72-e72.
doi:10.1016/j.atherosclerosis.2018.06.200 .

Novaković, Aleksandra, Marinko, Marija, Janković, Goran, Nenezić, Dragoslav, Stojanović, Ivan, Milojević, Predrag, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, "Cardioprotective effect of procyanidin B2" in Atherosclerosis, 275 (2018):e72-e72,
https://doi.org/10.1016/j.atherosclerosis.2018.06.200 . .

TY  - JOUR
AU  - Marinko, Marija
AU  - Janković, Goran
AU  - Nenezić, Dragoslav
AU  - Milojević, Predrag
AU  - Stojanović, Ivan
AU  - Kanjuh, Vladimir
AU  - Novaković, Aleksandra
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3191
AB  - In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K+ channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K+, whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca2+-free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive K-V channels, BKCa channels, and at least partly, K-ATP channels. In addition, not only the inhibition of extracellular Ca2+ influx, but regulation of the intracellular Ca2+ release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca2+-ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV.
PB  - Wiley, Hoboken
T2  - Phytotherapy Research
T1  - (-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels
VL  - 32
IS  - 2
SP  - 267
EP  - 275
DO  - 10.1002/ptr.5969
ER  - 

@article{
author = "Marinko, Marija and Janković, Goran and Nenezić, Dragoslav and Milojević, Predrag and Stojanović, Ivan and Kanjuh, Vladimir and Novaković, Aleksandra",
year = "2018",
abstract = "In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K+ channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K+, whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca2+-free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive K-V channels, BKCa channels, and at least partly, K-ATP channels. In addition, not only the inhibition of extracellular Ca2+ influx, but regulation of the intracellular Ca2+ release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca2+-ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV.",
publisher = "Wiley, Hoboken",
journal = "Phytotherapy Research",
title = "(-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels",
volume = "32",
number = "2",
pages = "267-275",
doi = "10.1002/ptr.5969"
}

Marinko, M., Janković, G., Nenezić, D., Milojević, P., Stojanović, I., Kanjuh, V.,& Novaković, A.. (2018). (-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels. in Phytotherapy Research
Wiley, Hoboken., 32(2), 267-275.
https://doi.org/10.1002/ptr.5969

Marinko M, Janković G, Nenezić D, Milojević P, Stojanović I, Kanjuh V, Novaković A. (-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels. in Phytotherapy Research. 2018;32(2):267-275.
doi:10.1002/ptr.5969 .

Marinko, Marija, Janković, Goran, Nenezić, Dragoslav, Milojević, Predrag, Stojanović, Ivan, Kanjuh, Vladimir, Novaković, Aleksandra, "(-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels" in Phytotherapy Research, 32, no. 2 (2018):267-275,
https://doi.org/10.1002/ptr.5969 . .

TY  - JOUR
AU  - Novaković, Aleksandra
AU  - Marinko, Marija
AU  - Stojanović, Ivan
AU  - Nenezić, Dragoslav
AU  - Milojević, Predrag
AU  - Kanjuh, Vladimir
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3114
AB  - Dyslipidemia is the leading risk factor for the development of atherosclerosis and associated consequences, such as coronary heart disease, ischemic cerebrovascular and peripheral vascular disease. These diseases are the major cause of mortality in the world and in Europe as well, where they are responsible for around 45% of all deaths. Treatment of dyslipidemia includes the use of statins, ezetimibe, fibrates, niacin, bile acids sequestrants and omega-3 fatty acids. Although statins play the major role in dyslipidemia treatment by reducing the risk of cardiovascular (CV) events by 30%, there is a need for additional new drugs that reduce the residual risk even more. PCSK9 inhibitors, apolipoprotein B (apoB) synthesis inhibitors, MTP inhibitors and CETP inhibitors are already approved for the specific indications, or are in the advanced stages of clinical investigation. Two PCSK9 inhibitors, alirocumab and evolocumab are approved for use in combination with statins for the treatment of heterozygous familial hypercholesterolemia (FH), but also in patients with clinical atherosclerotic CV diseases who require additional low-density lipoprotein cholesterol (LDL-C) level reduction. In addition, evolocumab is approved for use in patients with homozygous FH. Mipomersen, apoB synthesis inhibitor, lomitapide, and oral MTP inhibitor are currently approved in the treatment of patients with homozygous FH as an adjunct to the maximum tolerated doses of statins and other lipid-lowering drugs. Although the new lipid-lowering agents produce significant LDL-C level reduction, more clinical studies are necessary to confirm their efficacy and safety in dyslipidemia treatment.
AB  - Dislipidemije su vodeći faktor rizika za razvoj ateroskleroze i njenih posledica, kao što su koronarna bolest srca, ishemična cerebrovaskularna i periferna vaskularna bolest. Ove bolesti su glavni uzrok mortaliteta, kako u svetu tako i u Evropi, gde su odgovorne za 45% ukupne smrtnosti. Terapija dislipidemija uključuje primenu: statina, ezetimiba, fibrata, niacina, smola koje vezuju žučne kiseline i omega-3 masnih kiselina. Od pomenutih lekova, vodeću ulogu u terapiji dislipidemija imaju statini. Treba istaći da uprkos primeni statina, koji redukuju rizik od pojave kardiovaskularnih (KV) događaja za oko 30%, još uvek ostaje tzv. rezidualni rizik za nastanak KV događaja, što ukazuje da su potrebni novi lekovi koji će dalje redukovati rezidualni rizik. Novi lekovi u terapiji dislipidemija uključuju PCSK9 inhibitore, inhibitore sinteze apolipoproteina B (apoB), MTP inhibitore i CETP inhibitore, koji su ili već odobreni za primenu u određenim indikacijama, ili se nalaze u odmaklim fazama kliničkog ispitivanja. Alirokumab i evolokumab, dva PCSK9 inhibitora, odobrena su za primenu, u kombinaciji sa statinima, u terapiji heterozigotne familijarne hiperholesterolemije (FH), kao i kod bolesnika sa kliničkim aterosklerotičnim KV bolestima koji zahtevaju dodatnu redukciju nivoa lipoproteina male gustine (low-density lipoprotein cholesterol, LDL-C). Pored toga, evolokumab je odobren za primenu kod bolesnika sa homozigotnom FH. Mipomersen, inhibitor sinteze apoB, i lomitapid, oralni MTP inhibitor, su, odobreni za primenu samo kod bolesnika sa homozigotnom FH kao dodatak maksimalnoj tolerišućoj dozi statina i drugih hipolipemika. Iako novi hipolipemici značajno redukuju nivo LDL-C, neophodno je sprovesti studije, duže i sa većim brojem ispitanika, koje će potvrditi njihovu efikasnost i bezbednost i time omogućiti njihovu širu primenu u terapiji dislipidemija.
PB  - Univerzitet u Nišu - Medicinski fakultet, Niš
T2  - Acta medica Medianae
T1  - New drugs for the treatment of dyslipidemia
T1  - Novi lekovi u terapiji dislipidemija
VL  - 57
IS  - 1
SP  - 54
EP  - 63
DO  - 10.5633/amm.2018.0109
ER  - 

@article{
author = "Novaković, Aleksandra and Marinko, Marija and Stojanović, Ivan and Nenezić, Dragoslav and Milojević, Predrag and Kanjuh, Vladimir",
year = "2018",
abstract = "Dyslipidemia is the leading risk factor for the development of atherosclerosis and associated consequences, such as coronary heart disease, ischemic cerebrovascular and peripheral vascular disease. These diseases are the major cause of mortality in the world and in Europe as well, where they are responsible for around 45% of all deaths. Treatment of dyslipidemia includes the use of statins, ezetimibe, fibrates, niacin, bile acids sequestrants and omega-3 fatty acids. Although statins play the major role in dyslipidemia treatment by reducing the risk of cardiovascular (CV) events by 30%, there is a need for additional new drugs that reduce the residual risk even more. PCSK9 inhibitors, apolipoprotein B (apoB) synthesis inhibitors, MTP inhibitors and CETP inhibitors are already approved for the specific indications, or are in the advanced stages of clinical investigation. Two PCSK9 inhibitors, alirocumab and evolocumab are approved for use in combination with statins for the treatment of heterozygous familial hypercholesterolemia (FH), but also in patients with clinical atherosclerotic CV diseases who require additional low-density lipoprotein cholesterol (LDL-C) level reduction. In addition, evolocumab is approved for use in patients with homozygous FH. Mipomersen, apoB synthesis inhibitor, lomitapide, and oral MTP inhibitor are currently approved in the treatment of patients with homozygous FH as an adjunct to the maximum tolerated doses of statins and other lipid-lowering drugs. Although the new lipid-lowering agents produce significant LDL-C level reduction, more clinical studies are necessary to confirm their efficacy and safety in dyslipidemia treatment., Dislipidemije su vodeći faktor rizika za razvoj ateroskleroze i njenih posledica, kao što su koronarna bolest srca, ishemična cerebrovaskularna i periferna vaskularna bolest. Ove bolesti su glavni uzrok mortaliteta, kako u svetu tako i u Evropi, gde su odgovorne za 45% ukupne smrtnosti. Terapija dislipidemija uključuje primenu: statina, ezetimiba, fibrata, niacina, smola koje vezuju žučne kiseline i omega-3 masnih kiselina. Od pomenutih lekova, vodeću ulogu u terapiji dislipidemija imaju statini. Treba istaći da uprkos primeni statina, koji redukuju rizik od pojave kardiovaskularnih (KV) događaja za oko 30%, još uvek ostaje tzv. rezidualni rizik za nastanak KV događaja, što ukazuje da su potrebni novi lekovi koji će dalje redukovati rezidualni rizik. Novi lekovi u terapiji dislipidemija uključuju PCSK9 inhibitore, inhibitore sinteze apolipoproteina B (apoB), MTP inhibitore i CETP inhibitore, koji su ili već odobreni za primenu u određenim indikacijama, ili se nalaze u odmaklim fazama kliničkog ispitivanja. Alirokumab i evolokumab, dva PCSK9 inhibitora, odobrena su za primenu, u kombinaciji sa statinima, u terapiji heterozigotne familijarne hiperholesterolemije (FH), kao i kod bolesnika sa kliničkim aterosklerotičnim KV bolestima koji zahtevaju dodatnu redukciju nivoa lipoproteina male gustine (low-density lipoprotein cholesterol, LDL-C). Pored toga, evolokumab je odobren za primenu kod bolesnika sa homozigotnom FH. Mipomersen, inhibitor sinteze apoB, i lomitapid, oralni MTP inhibitor, su, odobreni za primenu samo kod bolesnika sa homozigotnom FH kao dodatak maksimalnoj tolerišućoj dozi statina i drugih hipolipemika. Iako novi hipolipemici značajno redukuju nivo LDL-C, neophodno je sprovesti studije, duže i sa većim brojem ispitanika, koje će potvrditi njihovu efikasnost i bezbednost i time omogućiti njihovu širu primenu u terapiji dislipidemija.",
publisher = "Univerzitet u Nišu - Medicinski fakultet, Niš",
journal = "Acta medica Medianae",
title = "New drugs for the treatment of dyslipidemia, Novi lekovi u terapiji dislipidemija",
volume = "57",
number = "1",
pages = "54-63",
doi = "10.5633/amm.2018.0109"
}

Novaković, A., Marinko, M., Stojanović, I., Nenezić, D., Milojević, P.,& Kanjuh, V.. (2018). New drugs for the treatment of dyslipidemia. in Acta medica Medianae
Univerzitet u Nišu - Medicinski fakultet, Niš., 57(1), 54-63.
https://doi.org/10.5633/amm.2018.0109

Novaković A, Marinko M, Stojanović I, Nenezić D, Milojević P, Kanjuh V. New drugs for the treatment of dyslipidemia. in Acta medica Medianae. 2018;57(1):54-63.
doi:10.5633/amm.2018.0109 .

Novaković, Aleksandra, Marinko, Marija, Stojanović, Ivan, Nenezić, Dragoslav, Milojević, Predrag, Kanjuh, Vladimir, "New drugs for the treatment of dyslipidemia" in Acta medica Medianae, 57, no. 1 (2018):54-63,
https://doi.org/10.5633/amm.2018.0109 . .

TY  - JOUR
AU  - Novaković, Aleksandra
AU  - Marinko, Marija
AU  - Janković, Goran
AU  - Stojanović, Ivan
AU  - Milojević, Predrag
AU  - Nenezić, Dragoslav
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2972
AB  - The aim of the present study was to investigate and characterize vasorelaxant effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the mechanisms of its protective effect against vascular risk. Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations. Among K+ channel blockers, iberiotoxin, a selective blocker of large conductance Ca2+-activated K+ channels (BKCa), abolished procyanidin B2-induced relaxation, glibenclamide, a selective ATP-sensitive K+(K-ATP) channels blocker, induced partial inhibition, while 4-aminopyridine, a blocker of voltage-gated K+(K-V) channels, and TRAM-34, an inhibitor of intermediate-conductance Ca2+-activated K+(IKCa) channels, slightly reduced maximal relaxation of HIMA. Further, procyanidin B2 relaxed contraction induced by phenylephrine in Ca2+-free Krebs solution, but had no effect on contraction induced by caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor, significantly reduced relaxation of HIMA produced by procyanidin B2. These results demonstrate that procyanidin B2 produces endothelium-dependent relaxation of HIMA pre-contracted by phenylephrine. This effect is primarily the result of an increased NO synthesis and secretion by endothelial cells and partially of prostacyclin, although it involves activation of BKCa and K-ATP, as well as K-V and IKCa channels in high concentrations of procyanidin B2.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmacology
T1  - Endothelium-dependent vasorelaxant effect of procyanidin B2 on human internal mammary artery
VL  - 807
SP  - 75
EP  - 81
DO  - 10.1016/j.ejphar.2017.04.015
ER  - 

@article{
author = "Novaković, Aleksandra and Marinko, Marija and Janković, Goran and Stojanović, Ivan and Milojević, Predrag and Nenezić, Dragoslav and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei",
year = "2017",
abstract = "The aim of the present study was to investigate and characterize vasorelaxant effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the mechanisms of its protective effect against vascular risk. Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations. Among K+ channel blockers, iberiotoxin, a selective blocker of large conductance Ca2+-activated K+ channels (BKCa), abolished procyanidin B2-induced relaxation, glibenclamide, a selective ATP-sensitive K+(K-ATP) channels blocker, induced partial inhibition, while 4-aminopyridine, a blocker of voltage-gated K+(K-V) channels, and TRAM-34, an inhibitor of intermediate-conductance Ca2+-activated K+(IKCa) channels, slightly reduced maximal relaxation of HIMA. Further, procyanidin B2 relaxed contraction induced by phenylephrine in Ca2+-free Krebs solution, but had no effect on contraction induced by caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor, significantly reduced relaxation of HIMA produced by procyanidin B2. These results demonstrate that procyanidin B2 produces endothelium-dependent relaxation of HIMA pre-contracted by phenylephrine. This effect is primarily the result of an increased NO synthesis and secretion by endothelial cells and partially of prostacyclin, although it involves activation of BKCa and K-ATP, as well as K-V and IKCa channels in high concentrations of procyanidin B2.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmacology",
title = "Endothelium-dependent vasorelaxant effect of procyanidin B2 on human internal mammary artery",
volume = "807",
pages = "75-81",
doi = "10.1016/j.ejphar.2017.04.015"
}

Novaković, A., Marinko, M., Janković, G., Stojanović, I., Milojević, P., Nenezić, D., Kanjuh, V., Yang, Q.,& He, G.. (2017). Endothelium-dependent vasorelaxant effect of procyanidin B2 on human internal mammary artery. in European Journal of Pharmacology
Elsevier Science BV, Amsterdam., 807, 75-81.
https://doi.org/10.1016/j.ejphar.2017.04.015

Novaković A, Marinko M, Janković G, Stojanović I, Milojević P, Nenezić D, Kanjuh V, Yang Q, He G. Endothelium-dependent vasorelaxant effect of procyanidin B2 on human internal mammary artery. in European Journal of Pharmacology. 2017;807:75-81.
doi:10.1016/j.ejphar.2017.04.015 .

Novaković, Aleksandra, Marinko, Marija, Janković, Goran, Stojanović, Ivan, Milojević, Predrag, Nenezić, Dragoslav, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, "Endothelium-dependent vasorelaxant effect of procyanidin B2 on human internal mammary artery" in European Journal of Pharmacology, 807 (2017):75-81,
https://doi.org/10.1016/j.ejphar.2017.04.015 . .

TY  - JOUR
AU  - Hou, Hai-Tao
AU  - Wang, Jun
AU  - Wang, Zheng-Qing
AU  - Liu, Xiao-Cheng
AU  - Marinko, Marija
AU  - Novaković, Aleksandra
AU  - Yang, Qin
AU  - He, Guo-Wei
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2525
AB  - Background. Graft spasm remains challenging in coronary artery bypass grafting (CABG). Calcium antagonists are commonly used in patients with coronary artery disease. This study investigated the inhibitory effect of third-generation dihydropyridine calcium channel antagonist benidipine on the vasoconstriction induced by various vasoconstrictors in the human internalmammary artery(IMA). Methods. Isolated human IMA rings (N = 65, taken from 37 patients undergoing CABG) were studied in a myograph in 2 ways: the relaxing effect of benidipine on vasoconstrictor-induced precontraction by KCl and U46619 and the depressing effect of benidipine at plasma concentrations on the contraction. Enzyme-linked immunosorbent assay (ELISA) was used to measure the change of the protein related to the L-type calcium channel. Results. Benidipine caused more relaxation in KCl-contracted (86.7% +/- 3.3%; n = 12) than in U46619-contracted (63.8% +/- 5.3%; n = 8; p  lt  0.001) IMA rings. Pretreatment of IMA with plasma concentrations of benidipine (-6.92 log M) significantly depressed subsequent contraction by KCl (from 17.3 +/- 2.7 mN to 7.4 +/- 1.2 mN; n = 6; p  lt  0.05) but did not significantly affect the contraction caused by U46619. Benidipine also caused a decrease of caveolin (CaV) 1.2 protein content (0.55 +/- 0.02 versus 0.63 +/- 0.02 mg/mL; p  lt  0.05). Conclusions. We conclude that in human IMA, the third-generation dihydropyridine calcium channel antagonist benidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Use of benidipine in patients undergoing CABG may provide vasorelaxant or antispastic effects in the grafts.
PB  - Elsevier Science Inc, New York
T2  - Annals of Thoracic Surgery
T1  - Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications
VL  - 101
IS  - 5
SP  - 1789
EP  - 1795
DO  - 10.1016/j.athoracsur.2015.10.029
ER  - 

@article{
author = "Hou, Hai-Tao and Wang, Jun and Wang, Zheng-Qing and Liu, Xiao-Cheng and Marinko, Marija and Novaković, Aleksandra and Yang, Qin and He, Guo-Wei",
year = "2016",
abstract = "Background. Graft spasm remains challenging in coronary artery bypass grafting (CABG). Calcium antagonists are commonly used in patients with coronary artery disease. This study investigated the inhibitory effect of third-generation dihydropyridine calcium channel antagonist benidipine on the vasoconstriction induced by various vasoconstrictors in the human internalmammary artery(IMA). Methods. Isolated human IMA rings (N = 65, taken from 37 patients undergoing CABG) were studied in a myograph in 2 ways: the relaxing effect of benidipine on vasoconstrictor-induced precontraction by KCl and U46619 and the depressing effect of benidipine at plasma concentrations on the contraction. Enzyme-linked immunosorbent assay (ELISA) was used to measure the change of the protein related to the L-type calcium channel. Results. Benidipine caused more relaxation in KCl-contracted (86.7% +/- 3.3%; n = 12) than in U46619-contracted (63.8% +/- 5.3%; n = 8; p  lt  0.001) IMA rings. Pretreatment of IMA with plasma concentrations of benidipine (-6.92 log M) significantly depressed subsequent contraction by KCl (from 17.3 +/- 2.7 mN to 7.4 +/- 1.2 mN; n = 6; p  lt  0.05) but did not significantly affect the contraction caused by U46619. Benidipine also caused a decrease of caveolin (CaV) 1.2 protein content (0.55 +/- 0.02 versus 0.63 +/- 0.02 mg/mL; p  lt  0.05). Conclusions. We conclude that in human IMA, the third-generation dihydropyridine calcium channel antagonist benidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Use of benidipine in patients undergoing CABG may provide vasorelaxant or antispastic effects in the grafts.",
publisher = "Elsevier Science Inc, New York",
journal = "Annals of Thoracic Surgery",
title = "Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications",
volume = "101",
number = "5",
pages = "1789-1795",
doi = "10.1016/j.athoracsur.2015.10.029"
}

Hou, H., Wang, J., Wang, Z., Liu, X., Marinko, M., Novaković, A., Yang, Q.,& He, G.. (2016). Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications. in Annals of Thoracic Surgery
Elsevier Science Inc, New York., 101(5), 1789-1795.
https://doi.org/10.1016/j.athoracsur.2015.10.029

Hou H, Wang J, Wang Z, Liu X, Marinko M, Novaković A, Yang Q, He G. Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications. in Annals of Thoracic Surgery. 2016;101(5):1789-1795.
doi:10.1016/j.athoracsur.2015.10.029 .

Hou, Hai-Tao, Wang, Jun, Wang, Zheng-Qing, Liu, Xiao-Cheng, Marinko, Marija, Novaković, Aleksandra, Yang, Qin, He, Guo-Wei, "Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications" in Annals of Thoracic Surgery, 101, no. 5 (2016):1789-1795,
https://doi.org/10.1016/j.athoracsur.2015.10.029 . .

TY  - CONF
AU  - Novaković, Aleksandra
AU  - Marinko, Marija
AU  - Vranić, Aleksandra
AU  - Janković, Goran
AU  - Stojanović, Ivan
AU  - Milojević, Predrag
AU  - Ugrešić, Nenad
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2442
PB  - Elsevier Ireland Ltd, Clare
C3  - Atherosclerosis
T1  - Epicatechin induced vasorelaxation of human internal mammary artery
VL  - 241
IS  - 1
SP  - e50
EP  - e50
DO  - 10.1016/j.atherosclerosis.2015.04.178
ER  - 

@conference{
author = "Novaković, Aleksandra and Marinko, Marija and Vranić, Aleksandra and Janković, Goran and Stojanović, Ivan and Milojević, Predrag and Ugrešić, Nenad and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei",
year = "2015",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Atherosclerosis",
title = "Epicatechin induced vasorelaxation of human internal mammary artery",
volume = "241",
number = "1",
pages = "e50-e50",
doi = "10.1016/j.atherosclerosis.2015.04.178"
}

Novaković, A., Marinko, M., Vranić, A., Janković, G., Stojanović, I., Milojević, P., Ugrešić, N., Kanjuh, V., Yang, Q.,& He, G.. (2015). Epicatechin induced vasorelaxation of human internal mammary artery. in Atherosclerosis
Elsevier Ireland Ltd, Clare., 241(1), e50-e50.
https://doi.org/10.1016/j.atherosclerosis.2015.04.178

Novaković A, Marinko M, Vranić A, Janković G, Stojanović I, Milojević P, Ugrešić N, Kanjuh V, Yang Q, He G. Epicatechin induced vasorelaxation of human internal mammary artery. in Atherosclerosis. 2015;241(1):e50-e50.
doi:10.1016/j.atherosclerosis.2015.04.178 .

Novaković, Aleksandra, Marinko, Marija, Vranić, Aleksandra, Janković, Goran, Stojanović, Ivan, Milojević, Predrag, Ugrešić, Nenad, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, "Epicatechin induced vasorelaxation of human internal mammary artery" in Atherosclerosis, 241, no. 1 (2015):e50-e50,
https://doi.org/10.1016/j.atherosclerosis.2015.04.178 . .

TY  - JOUR
AU  - Marinko, Marija
AU  - Novaković, Aleksandra
AU  - Nenezić, Dragoslav
AU  - Stojanović, Ivan
AU  - Milojević, Predrag
AU  - Jović, Miomir
AU  - Ugrešić, Nenad
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2461
AB  - As we previously demonstrated the role of different K+ channels in the action of nicorandil on human saphenous vein (HSV) and human internal mammary artery (HIMA), this study aimed to analyse the contribution of the cGMP pathway in nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the K+ channel-activating effect of nicorandil. An inhibitor of soluble guanylate cyclase (GC), ODQ, significantly inhibited nicorandil-induced relaxation, while ODQ plus glibenclamide, a selective ATP-sensitive K+ (KATP) channel inhibitor, produced a further inhibition of both vessels. In HSV, ODQ in combination with 4-aminopyridine, a blocker of voltage-gated K+ (K-V) channels, did not modify the concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus iberiotoxin, a selective blocker of large-conductance Ca2+-activated K+ (BKCa) channels, produced greater inhibition than ODQ alone. We showed that the cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on HSV and HIMA. It seems that nicorandil directly opens KATP channels in both vessels and BKCa channels in HIMA, although it is possible that stimulation of GC contributes to KATP channels activation in HIMA. Contrary, the activation of K-V channels in HSV is probably due to GC activation and increased levels of cGMP.
PB  - Japanese Pharmacological Soc, Kyoto
T2  - Journal of Pharmacological Sciences
T1  - Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts
VL  - 128
IS  - 2
SP  - 59
EP  - 64
DO  - 10.1016/j.jphs.2015.03.003
ER  - 

@article{
author = "Marinko, Marija and Novaković, Aleksandra and Nenezić, Dragoslav and Stojanović, Ivan and Milojević, Predrag and Jović, Miomir and Ugrešić, Nenad and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei",
year = "2015",
abstract = "As we previously demonstrated the role of different K+ channels in the action of nicorandil on human saphenous vein (HSV) and human internal mammary artery (HIMA), this study aimed to analyse the contribution of the cGMP pathway in nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the K+ channel-activating effect of nicorandil. An inhibitor of soluble guanylate cyclase (GC), ODQ, significantly inhibited nicorandil-induced relaxation, while ODQ plus glibenclamide, a selective ATP-sensitive K+ (KATP) channel inhibitor, produced a further inhibition of both vessels. In HSV, ODQ in combination with 4-aminopyridine, a blocker of voltage-gated K+ (K-V) channels, did not modify the concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus iberiotoxin, a selective blocker of large-conductance Ca2+-activated K+ (BKCa) channels, produced greater inhibition than ODQ alone. We showed that the cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on HSV and HIMA. It seems that nicorandil directly opens KATP channels in both vessels and BKCa channels in HIMA, although it is possible that stimulation of GC contributes to KATP channels activation in HIMA. Contrary, the activation of K-V channels in HSV is probably due to GC activation and increased levels of cGMP.",
publisher = "Japanese Pharmacological Soc, Kyoto",
journal = "Journal of Pharmacological Sciences",
title = "Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts",
volume = "128",
number = "2",
pages = "59-64",
doi = "10.1016/j.jphs.2015.03.003"
}

Marinko, M., Novaković, A., Nenezić, D., Stojanović, I., Milojević, P., Jović, M., Ugrešić, N., Kanjuh, V., Yang, Q.,& He, G.. (2015). Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts. in Journal of Pharmacological Sciences
Japanese Pharmacological Soc, Kyoto., 128(2), 59-64.
https://doi.org/10.1016/j.jphs.2015.03.003

Marinko M, Novaković A, Nenezić D, Stojanović I, Milojević P, Jović M, Ugrešić N, Kanjuh V, Yang Q, He G. Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts. in Journal of Pharmacological Sciences. 2015;128(2):59-64.
doi:10.1016/j.jphs.2015.03.003 .

Marinko, Marija, Novaković, Aleksandra, Nenezić, Dragoslav, Stojanović, Ivan, Milojević, Predrag, Jović, Miomir, Ugrešić, Nenad, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, "Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts" in Journal of Pharmacological Sciences, 128, no. 2 (2015):59-64,
https://doi.org/10.1016/j.jphs.2015.03.003 . .

TY  - JOUR
AU  - Novaković, Aleksandra
AU  - Marinko, Marija
AU  - Vranić, Aleksandra
AU  - Janković, Goran
AU  - Milojević, Predrag
AU  - Stojanović, Ivan
AU  - Nenezić, Dragoslav
AU  - Ugrešić, Nenad
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - He, Guo-Wei
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2439
AB  - Evidences have suggested that flavanol compound (-)-epicatechin is associated with reduced risk of cardiovascular diseases. One of the mechanisms of its cardioprotective effect is vasodilation. However, the exact mechanisms by which (-)-epicatechin causes vasodilation are not yet clearly defined. The aims of the present study were to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human internal mammary artery (HIMA) and to determine the mechanisms underlying its vasorelaxation. Our results showed that (-)-epicatechin induced a concentration-dependent relaxation of RNA rings pre-contracted by phenylephrine. Among the K+ channel blockers, 4-aminopyricline (4-AP) and margatoxin, blockers of voltage gated K+ (K-V) channels, and glibenclamide, a selective ATP sensitive K+ (K-ATP,) channels blocker, partly inhibited the (-)-epicatechin-induced relaxation of HIMA, while iberiotoxin, a most selective blocker of large conductance Ca2+-activated K+ channels (BKCa), almost completely inhibited the relaxation. In rings pre-contracted by 80 mM K+, (-)-epicatechin induced partial relaxation of HIMA, whereas in Ca2+-free medium, (-)-epicatechin completely relaxed HIMA rings pre-contracted by phenylephrine and caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor, slightly antagonized (-)-epicatechin-induced relaxation of HIMA pre-contracted by phenylephrine. These results suggest that (-)-epicatechin induces strong endothelium independent relaxation of HIMA pre-contracted by phenylephrine whilst 4-AP- and rnargatoxin-sensitive K-V channels, as well as BKCa and K-ATP channels, located in vascular smooth muscle, mediate this relaxation. In addition, it seems that (-)-epicatechin could inhibit influx of extracellular Ca2+, interfere with intracellular Ca2+ release and re uptake by the sarcoplasmic reticulum.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmacology
T1  - Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin
VL  - 762
SP  - 306
EP  - 312
DO  - 10.1016/j.ejphar.2015.05.066
ER  - 

@article{
author = "Novaković, Aleksandra and Marinko, Marija and Vranić, Aleksandra and Janković, Goran and Milojević, Predrag and Stojanović, Ivan and Nenezić, Dragoslav and Ugrešić, Nenad and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei",
year = "2015",
abstract = "Evidences have suggested that flavanol compound (-)-epicatechin is associated with reduced risk of cardiovascular diseases. One of the mechanisms of its cardioprotective effect is vasodilation. However, the exact mechanisms by which (-)-epicatechin causes vasodilation are not yet clearly defined. The aims of the present study were to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human internal mammary artery (HIMA) and to determine the mechanisms underlying its vasorelaxation. Our results showed that (-)-epicatechin induced a concentration-dependent relaxation of RNA rings pre-contracted by phenylephrine. Among the K+ channel blockers, 4-aminopyricline (4-AP) and margatoxin, blockers of voltage gated K+ (K-V) channels, and glibenclamide, a selective ATP sensitive K+ (K-ATP,) channels blocker, partly inhibited the (-)-epicatechin-induced relaxation of HIMA, while iberiotoxin, a most selective blocker of large conductance Ca2+-activated K+ channels (BKCa), almost completely inhibited the relaxation. In rings pre-contracted by 80 mM K+, (-)-epicatechin induced partial relaxation of HIMA, whereas in Ca2+-free medium, (-)-epicatechin completely relaxed HIMA rings pre-contracted by phenylephrine and caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor, slightly antagonized (-)-epicatechin-induced relaxation of HIMA pre-contracted by phenylephrine. These results suggest that (-)-epicatechin induces strong endothelium independent relaxation of HIMA pre-contracted by phenylephrine whilst 4-AP- and rnargatoxin-sensitive K-V channels, as well as BKCa and K-ATP channels, located in vascular smooth muscle, mediate this relaxation. In addition, it seems that (-)-epicatechin could inhibit influx of extracellular Ca2+, interfere with intracellular Ca2+ release and re uptake by the sarcoplasmic reticulum.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmacology",
title = "Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin",
volume = "762",
pages = "306-312",
doi = "10.1016/j.ejphar.2015.05.066"
}

Novaković, A., Marinko, M., Vranić, A., Janković, G., Milojević, P., Stojanović, I., Nenezić, D., Ugrešić, N., Kanjuh, V., Yang, Q.,& He, G.. (2015). Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin. in European Journal of Pharmacology
Elsevier Science BV, Amsterdam., 762, 306-312.
https://doi.org/10.1016/j.ejphar.2015.05.066

Novaković A, Marinko M, Vranić A, Janković G, Milojević P, Stojanović I, Nenezić D, Ugrešić N, Kanjuh V, Yang Q, He G. Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin. in European Journal of Pharmacology. 2015;762:306-312.
doi:10.1016/j.ejphar.2015.05.066 .

Novaković, Aleksandra, Marinko, Marija, Vranić, Aleksandra, Janković, Goran, Milojević, Predrag, Stojanović, Ivan, Nenezić, Dragoslav, Ugrešić, Nenad, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, "Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin" in European Journal of Pharmacology, 762 (2015):306-312,
https://doi.org/10.1016/j.ejphar.2015.05.066 . .

TY  - CONF
AU  - Novaković, Aleksandra
AU  - Marinko, Marija
AU  - Milojević, Predrag
AU  - Babić, Milan
AU  - Stojanović, Ivan
AU  - Jović, Miomir
AU  - Nenezić, Dragoslav
AU  - Ugrešić, Nenad
AU  - Yang, Qin
AU  - He, Guo-Wei
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1728
PB  - Lippincott Williams & Wilkins, Philadelphia
C3  - Circulation
T1  - Relaxation of arterial graft induced by nicorandil
VL  - 125
IS  - 19
SP  - e184
EP  - e184
DO  - 10.1161/CIR.0b013e31824fcdb3
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1728
ER  - 

@conference{
author = "Novaković, Aleksandra and Marinko, Marija and Milojević, Predrag and Babić, Milan and Stojanović, Ivan and Jović, Miomir and Nenezić, Dragoslav and Ugrešić, Nenad and Yang, Qin and He, Guo-Wei",
year = "2012",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Circulation",
title = "Relaxation of arterial graft induced by nicorandil",
volume = "125",
number = "19",
pages = "e184-e184",
doi = "10.1161/CIR.0b013e31824fcdb3",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1728"
}

Novaković, A., Marinko, M., Milojević, P., Babić, M., Stojanović, I., Jović, M., Nenezić, D., Ugrešić, N., Yang, Q.,& He, G.. (2012). Relaxation of arterial graft induced by nicorandil. in Circulation
Lippincott Williams & Wilkins, Philadelphia., 125(19), e184-e184.
https://doi.org/10.1161/CIR.0b013e31824fcdb3
https://hdl.handle.net/21.15107/rcub_farfar_1728

Novaković A, Marinko M, Milojević P, Babić M, Stojanović I, Jović M, Nenezić D, Ugrešić N, Yang Q, He G. Relaxation of arterial graft induced by nicorandil. in Circulation. 2012;125(19):e184-e184.
doi:10.1161/CIR.0b013e31824fcdb3
https://hdl.handle.net/21.15107/rcub_farfar_1728 .

Novaković, Aleksandra, Marinko, Marija, Milojević, Predrag, Babić, Milan, Stojanović, Ivan, Jović, Miomir, Nenezić, Dragoslav, Ugrešić, Nenad, Yang, Qin, He, Guo-Wei, "Relaxation of arterial graft induced by nicorandil" in Circulation, 125, no. 19 (2012):e184-e184,
https://doi.org/10.1161/CIR.0b013e31824fcdb3 .,
https://hdl.handle.net/21.15107/rcub_farfar_1728 .

TY  - JOUR
AU  - Marinko, Marija
AU  - Novaković, Aleksandra
AU  - Divac, Tatjana
AU  - Milojević, Predrag
AU  - Nenezić, Dragoslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1831
AB  - Anticoagulants are effective agents for the prevention and treatment of thrombosis and thromboembolic complications, which represent a common cause of morbidity and mortality. Despite their clinical efficiency, traditional anticoagulants are all associated with significant drawbacks. As a result, modulation of the coagulation process represents an important target in the development of new oral and parenteral anticoagulants today. The new oral anticoagulants selectively target thrombin (ximelagatran, dabigatran etexilate) or factor Xa (rivaroxaban, apixaban, edoxaban). Unlike the traditional anticoagulants, vitamin K antagonists, these drugs have rapid onset of action and a relatively wide therapeutic range, do not require routine prothrombin time (PT) monitoring and have low potential for food and drug interaction. The new parenteral anticoagulants achieve their effects through indirect (semuloparin, idrabiotaparinux) or direct inhibition of factor Xa (otamixaban), as well as through inhibition of coagulation factor IXa (RB006). The main characteristics of these agents are a rapid onset of action and a predictable anticoagulant effect, whereby the most of them can be rapidly neutralized by an adequate antidote.
AB  - Antikoagulantni lekovi su delotvorni u prevenciji i lečenju tromboze i tromboembolijskih komplikacija, koje su čest uzrok morbiditeta i mortaliteta. Ipak, uprkos kliničkoj delotvornosti, standardni antikoagulansi poseduju značajne nedostatke. Zbog toga, modulacija procesa koagulacije danas predstavlja značajnu metu za razvoj novih, oralnih i parenteralnih, antikoagulanasa. Novi oralni antikoagulansi deluju selektivno na trombin (ksimelagatran, dabigatran eteksilat) ili na faktor koagulacije Xa (rivaroksaban, apiksaban, edoksaban). Za razliku od standardnih antikoagulanasa, antagonista vitamina K, imaju brz početak dejstva i relativno veliku terapijsku širinu, ne zahtevaju laboratorijsku kontrolu protrombinskog vremena (PT), i retko stupaju u interakcije sa hranom i lekovima. Novi parenteralni antikoagulansi svoje antikoagulantno dejstvo ostvaruju indirektnom (semuloparin, idrabiotaparinuks) ili direktnom inhibicijom faktora Xa (otamiksaban), kao i inhibicijom faktora koagulacije IXa (RB006). Glavne karakteristike ovih lekova su brz početak dejstva i predvidljiv antikoagulantni efekat, a kod većine je moguće postići brzu neutralizaciju adekvatnim antidotom.
PB  - Srpsko lekarsko društvo - Okružna podružnica Kragujevac, Kragujevac
T2  - Medicinski časopis
T1  - New anticoagulant drugs
T1  - Novi antikoagulantni lekovi
VL  - 46
IS  - 3
SP  - 145
EP  - 154
DO  - 10.5937/mckg46-1612
ER  - 

@article{
author = "Marinko, Marija and Novaković, Aleksandra and Divac, Tatjana and Milojević, Predrag and Nenezić, Dragoslav",
year = "2012",
abstract = "Anticoagulants are effective agents for the prevention and treatment of thrombosis and thromboembolic complications, which represent a common cause of morbidity and mortality. Despite their clinical efficiency, traditional anticoagulants are all associated with significant drawbacks. As a result, modulation of the coagulation process represents an important target in the development of new oral and parenteral anticoagulants today. The new oral anticoagulants selectively target thrombin (ximelagatran, dabigatran etexilate) or factor Xa (rivaroxaban, apixaban, edoxaban). Unlike the traditional anticoagulants, vitamin K antagonists, these drugs have rapid onset of action and a relatively wide therapeutic range, do not require routine prothrombin time (PT) monitoring and have low potential for food and drug interaction. The new parenteral anticoagulants achieve their effects through indirect (semuloparin, idrabiotaparinux) or direct inhibition of factor Xa (otamixaban), as well as through inhibition of coagulation factor IXa (RB006). The main characteristics of these agents are a rapid onset of action and a predictable anticoagulant effect, whereby the most of them can be rapidly neutralized by an adequate antidote., Antikoagulantni lekovi su delotvorni u prevenciji i lečenju tromboze i tromboembolijskih komplikacija, koje su čest uzrok morbiditeta i mortaliteta. Ipak, uprkos kliničkoj delotvornosti, standardni antikoagulansi poseduju značajne nedostatke. Zbog toga, modulacija procesa koagulacije danas predstavlja značajnu metu za razvoj novih, oralnih i parenteralnih, antikoagulanasa. Novi oralni antikoagulansi deluju selektivno na trombin (ksimelagatran, dabigatran eteksilat) ili na faktor koagulacije Xa (rivaroksaban, apiksaban, edoksaban). Za razliku od standardnih antikoagulanasa, antagonista vitamina K, imaju brz početak dejstva i relativno veliku terapijsku širinu, ne zahtevaju laboratorijsku kontrolu protrombinskog vremena (PT), i retko stupaju u interakcije sa hranom i lekovima. Novi parenteralni antikoagulansi svoje antikoagulantno dejstvo ostvaruju indirektnom (semuloparin, idrabiotaparinuks) ili direktnom inhibicijom faktora Xa (otamiksaban), kao i inhibicijom faktora koagulacije IXa (RB006). Glavne karakteristike ovih lekova su brz početak dejstva i predvidljiv antikoagulantni efekat, a kod većine je moguće postići brzu neutralizaciju adekvatnim antidotom.",
publisher = "Srpsko lekarsko društvo - Okružna podružnica Kragujevac, Kragujevac",
journal = "Medicinski časopis",
title = "New anticoagulant drugs, Novi antikoagulantni lekovi",
volume = "46",
number = "3",
pages = "145-154",
doi = "10.5937/mckg46-1612"
}

Marinko, M., Novaković, A., Divac, T., Milojević, P.,& Nenezić, D.. (2012). New anticoagulant drugs. in Medicinski časopis
Srpsko lekarsko društvo - Okružna podružnica Kragujevac, Kragujevac., 46(3), 145-154.
https://doi.org/10.5937/mckg46-1612

Marinko M, Novaković A, Divac T, Milojević P, Nenezić D. New anticoagulant drugs. in Medicinski časopis. 2012;46(3):145-154.
doi:10.5937/mckg46-1612 .

Marinko, Marija, Novaković, Aleksandra, Divac, Tatjana, Milojević, Predrag, Nenezić, Dragoslav, "New anticoagulant drugs" in Medicinski časopis, 46, no. 3 (2012):145-154,
https://doi.org/10.5937/mckg46-1612 . .

TY  - JOUR
AU  - Marinko, Marija
AU  - Ugrešić, Nenad
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1598
AB  - Insulin is anabolic and anti-catabolic hormone which has an important role in the metabolism of carbohydrates, proteins and lipids. In addition, insulin is the only agent used in all forms of diabetes mellitus for blood sugar control. Further, insulin is critical for the management of diabetic ketoacidosis, and it has an important role in the treatment of hyperglycemic, nonketotic coma and in the perioperative management of diabetic patients. Commercial insulin preparations, used today, represent result of recombinant DNA technology and have amino acid sequence identical to human insulin. Also, insulin analogs are produced by modifications in insulin molecule in order to improve pharmacokinetic properties. In this article, insulin preparations are described including their classification, characteristics and safety of use in a pregnancy.
AB  - Insulin je anabolički i antikatabolički hormon koji ima važnu ulogu u metabolizmu ugljenih hidrata, proteina i masti. Insulin je jedino sredstvo koje se koristi za kontrolu nivoa glukoze u krvi kod svih oblika dijabetes melitusa. Osim toga, važan je u terapiji dijabetesne ketoacidoze i ima značajnu ulogu u lečenju hiperglikemijske, hiperosmolarne, neketonske kome, kao i u perioperativnom tretmanu bolesnika sa dijabetesom. Preparati insulina koji se koriste u današnje vreme su rezultat rekombinantne DNK tehnologije i sadrže sekvencu aminokiselina identičnu humanom insulinu. Takođe, modifikacijama u molekulu insulina dobijeni su insulinski analozi sa ciljem poboljšavanja farmakokinetičkih osobina. U ovom radu su opisani preparati insulina, njihova podela, osnovne karakteristike i bezbednost primene u trudnoći.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Pharmacology of insulin
T1  - Farmakologija insulina
VL  - 61
IS  - 4
SP  - 383
EP  - 392
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1598
ER  - 

@article{
author = "Marinko, Marija and Ugrešić, Nenad",
year = "2011",
abstract = "Insulin is anabolic and anti-catabolic hormone which has an important role in the metabolism of carbohydrates, proteins and lipids. In addition, insulin is the only agent used in all forms of diabetes mellitus for blood sugar control. Further, insulin is critical for the management of diabetic ketoacidosis, and it has an important role in the treatment of hyperglycemic, nonketotic coma and in the perioperative management of diabetic patients. Commercial insulin preparations, used today, represent result of recombinant DNA technology and have amino acid sequence identical to human insulin. Also, insulin analogs are produced by modifications in insulin molecule in order to improve pharmacokinetic properties. In this article, insulin preparations are described including their classification, characteristics and safety of use in a pregnancy., Insulin je anabolički i antikatabolički hormon koji ima važnu ulogu u metabolizmu ugljenih hidrata, proteina i masti. Insulin je jedino sredstvo koje se koristi za kontrolu nivoa glukoze u krvi kod svih oblika dijabetes melitusa. Osim toga, važan je u terapiji dijabetesne ketoacidoze i ima značajnu ulogu u lečenju hiperglikemijske, hiperosmolarne, neketonske kome, kao i u perioperativnom tretmanu bolesnika sa dijabetesom. Preparati insulina koji se koriste u današnje vreme su rezultat rekombinantne DNK tehnologije i sadrže sekvencu aminokiselina identičnu humanom insulinu. Takođe, modifikacijama u molekulu insulina dobijeni su insulinski analozi sa ciljem poboljšavanja farmakokinetičkih osobina. U ovom radu su opisani preparati insulina, njihova podela, osnovne karakteristike i bezbednost primene u trudnoći.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Pharmacology of insulin, Farmakologija insulina",
volume = "61",
number = "4",
pages = "383-392",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1598"
}

Marinko, M.,& Ugrešić, N.. (2011). Pharmacology of insulin. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 61(4), 383-392.
https://hdl.handle.net/21.15107/rcub_farfar_1598

Marinko M, Ugrešić N. Pharmacology of insulin. in Arhiv za farmaciju. 2011;61(4):383-392.
https://hdl.handle.net/21.15107/rcub_farfar_1598 .

Marinko, Marija, Ugrešić, Nenad, "Pharmacology of insulin" in Arhiv za farmaciju, 61, no. 4 (2011):383-392,
https://hdl.handle.net/21.15107/rcub_farfar_1598 .