TY  - CONF
AU  - Janković, Goran
AU  - Bekčić, Stana
AU  - Marinković, Valentina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4596
AB  - The first batch is a medicinal product batch manufactured or imported after the
marketing authorization issuance, for the purpose of placing on the market (approved size).
Agency for Medicines and Medical Devices of Serbia (ALIMS) performs laboratory quality
control in accordance with approved the specification during the drug „shelf life“ and
analytical procedures during drug license issuing. Submitted to the ALIMS also: samples,
certificate of analysis (CoA) for analyzed batch, reference standards with appropriate
certificates and other requested documentation. Manufacturers experience indicates few
necessary things:
1. The outer packaging should contain the data approved in the formal completeness of
the variation, and not the data initially approved registration document;
2. List CoA data from the „shelf life”, not from „release“ certificate;
3. Analysis request, CoA and Batch Release Certificate should have the same batch size;
4. Submit the placebo and appropriate documentation for the analyzed sample;
5. Submit an unused reference standard and evidence that the cold chain has been
complied with as required;
6. The paper quality for printing drug instructions has to be 50 g/m2 ± 2% (GMP
guidelines);
7. If additional samples are submitted at the ALIMS request, the batch size has to be
corrected on the Request for Analysis, CoA and Batch Release Certificate
Quantities of drug samples for laboratory control provided by the client are given on
the ALIMS website. Sample size and delivery of immunological drugs (vaccines, serums,
toxins, allergens, blood and plasma drugs) are not the subject of this summary.
AB  - Prva serija je serija leka proizvedena ili uvezena posle izdavanja dozvole za lek, radi
stavljanja u promet, a čija je veličina odobrena u postupku izdavanja dozvole za lek. Agencija
za lekova i medicinska sredstva Srbije (ALIMS) obavlja laboratorijsku kontrolu kvaliteta prve
serije leka. Laboratorijska kontrola kvaliteta leka, vrši se u skladu sa specifikacijom u roku
trajanja leka („shelf life”) i analitičkim postupcima odobrenim u postupku izdavanja dozvole
za lek, postupku izmene/dopune dozvole za lek (varijacije), odnosno obnove dozvole za lek.
Uz zahtev za laboratorijsku kontrolu kvaliteta leka dostaviti ALIMS-u: uzorak serije leka,
sertifikat analize (CoA) za tu seriju leka, referentni standardi sa sertifikatima i druga
dokumentacija, na zahtev ALIMS. Praksa proizvođača ukazuje da je potrebno:
1. Na kutiji navesti podate sa formalne kompletnosti, a ne inicijalno odobrene pri
registracij;
2. Na CoA navesi podatke iz „shelf life”, a ne „release”sertiikata;
3. Zahtev za analizu, CoA i batch release sertifikatu treba da imaju istu veličinu serije;
4. Dostavi i placebo za analizirani uzorak kao i odgovarajuću dokumentacija za
placebo;
5. Dostaviti nekorišćen referentni standard i dokaz da je ispoštovan hladni lanac po
potrebi;
6. Kvalitet papira za štampanje uputstava za lek mora biti 50 g/m 2 ± 2% (GMP
smernice);
7. Ukoliko se dostavljaju dodatni uzorci na zahtev ALIMS mora se korigovati veličina
serije na Zahtevu za analizu, CoA i batch release sertifikatu.
Količine uzoraka lekova za laboratorijsku kontrolu koje dostavlja klijent date su na
sajtu ALIMS. Veličina i dostavljanje uzorka imunoloških lekova (vakcine, serumi, toksini,
alergeni) nije predmet ovog sažetka.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Drug manufacturers practice on meeting regulatory requirements for release of drug the first batch on the market in the Republic of Serbia
T1  - Praksa proizvođača lekova o ispunjenju regulatornih zahteva za puštanje prve serije leka u promet u Republici Srbiji
VL  - 72
IS  - 4 suplement
SP  - S528
EP  - S529
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4596
ER  - 

@conference{
author = "Janković, Goran and Bekčić, Stana and Marinković, Valentina",
year = "2022",
abstract = "The first batch is a medicinal product batch manufactured or imported after the
marketing authorization issuance, for the purpose of placing on the market (approved size).
Agency for Medicines and Medical Devices of Serbia (ALIMS) performs laboratory quality
control in accordance with approved the specification during the drug „shelf life“ and
analytical procedures during drug license issuing. Submitted to the ALIMS also: samples,
certificate of analysis (CoA) for analyzed batch, reference standards with appropriate
certificates and other requested documentation. Manufacturers experience indicates few
necessary things:
1. The outer packaging should contain the data approved in the formal completeness of
the variation, and not the data initially approved registration document;
2. List CoA data from the „shelf life”, not from „release“ certificate;
3. Analysis request, CoA and Batch Release Certificate should have the same batch size;
4. Submit the placebo and appropriate documentation for the analyzed sample;
5. Submit an unused reference standard and evidence that the cold chain has been
complied with as required;
6. The paper quality for printing drug instructions has to be 50 g/m2 ± 2% (GMP
guidelines);
7. If additional samples are submitted at the ALIMS request, the batch size has to be
corrected on the Request for Analysis, CoA and Batch Release Certificate
Quantities of drug samples for laboratory control provided by the client are given on
the ALIMS website. Sample size and delivery of immunological drugs (vaccines, serums,
toxins, allergens, blood and plasma drugs) are not the subject of this summary., Prva serija je serija leka proizvedena ili uvezena posle izdavanja dozvole za lek, radi
stavljanja u promet, a čija je veličina odobrena u postupku izdavanja dozvole za lek. Agencija
za lekova i medicinska sredstva Srbije (ALIMS) obavlja laboratorijsku kontrolu kvaliteta prve
serije leka. Laboratorijska kontrola kvaliteta leka, vrši se u skladu sa specifikacijom u roku
trajanja leka („shelf life”) i analitičkim postupcima odobrenim u postupku izdavanja dozvole
za lek, postupku izmene/dopune dozvole za lek (varijacije), odnosno obnove dozvole za lek.
Uz zahtev za laboratorijsku kontrolu kvaliteta leka dostaviti ALIMS-u: uzorak serije leka,
sertifikat analize (CoA) za tu seriju leka, referentni standardi sa sertifikatima i druga
dokumentacija, na zahtev ALIMS. Praksa proizvođača ukazuje da je potrebno:
1. Na kutiji navesti podate sa formalne kompletnosti, a ne inicijalno odobrene pri
registracij;
2. Na CoA navesi podatke iz „shelf life”, a ne „release”sertiikata;
3. Zahtev za analizu, CoA i batch release sertifikatu treba da imaju istu veličinu serije;
4. Dostavi i placebo za analizirani uzorak kao i odgovarajuću dokumentacija za
placebo;
5. Dostaviti nekorišćen referentni standard i dokaz da je ispoštovan hladni lanac po
potrebi;
6. Kvalitet papira za štampanje uputstava za lek mora biti 50 g/m 2 ± 2% (GMP
smernice);
7. Ukoliko se dostavljaju dodatni uzorci na zahtev ALIMS mora se korigovati veličina
serije na Zahtevu za analizu, CoA i batch release sertifikatu.
Količine uzoraka lekova za laboratorijsku kontrolu koje dostavlja klijent date su na
sajtu ALIMS. Veličina i dostavljanje uzorka imunoloških lekova (vakcine, serumi, toksini,
alergeni) nije predmet ovog sažetka.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Drug manufacturers practice on meeting regulatory requirements for release of drug the first batch on the market in the Republic of Serbia, Praksa proizvođača lekova o ispunjenju regulatornih zahteva za puštanje prve serije leka u promet u Republici Srbiji",
volume = "72",
number = "4 suplement",
pages = "S528-S529",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4596"
}

Janković, G., Bekčić, S.,& Marinković, V.. (2022). Drug manufacturers practice on meeting regulatory requirements for release of drug the first batch on the market in the Republic of Serbia. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S528-S529.
https://hdl.handle.net/21.15107/rcub_farfar_4596

Janković G, Bekčić S, Marinković V. Drug manufacturers practice on meeting regulatory requirements for release of drug the first batch on the market in the Republic of Serbia. in Arhiv za farmaciju. 2022;72(4 suplement):S528-S529.
https://hdl.handle.net/21.15107/rcub_farfar_4596 .

Janković, Goran, Bekčić, Stana, Marinković, Valentina, "Drug manufacturers practice on meeting regulatory requirements for release of drug the first batch on the market in the Republic of Serbia" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S528-S529,
https://hdl.handle.net/21.15107/rcub_farfar_4596 .

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  - Štulić, Miloš
AU  - Ćulafić, Đorđe
AU  - Boričić, Ivan
AU  - Stojković Lalošević, Milica
AU  - Pejić, Nina
AU  - Janković, Goran
AU  - Milovanović, Tamara
AU  - Ćulafić-Vojinović, Violeta
AU  - Vlaisavljević, Željko
AU  - Ćulafić, Milica
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4827
AB  - Intrahepatic cholestasis of pregnancy (ICP) is a gestation-specific liver disorder, defined most often as the onset of pruritus, usually from the third trimester of pregnancy, associated with abnormal liver test results and/or increased total serum bile acids and spontaneous relief after delivery. The 21-year-old patient was admitted to our ward in the 11th week of pregnancy due to raised liver enzymes. The first onset of pruritus and jaundice appeared a month before hospitalization. Immunology tests and Toxoplasma gondii were negative. We excluded viral etiology, while alpha-1-antitrypsin, serum and urine copper levels, and thyroid hormones were within the reference values. The patient denied she had taken any medicines and herbal preparations before and during pregnancy. Total bile acids in the serum were significantly elevated (242 μmol/L). The abdominal ultrasound revealed a regular finding. Liver biopsy suggested a cholestatic liver disorder. After a presentation of all risks, the patient decided to stop the pregnancy. After a month, the hepatogram was within the reference values. Very rarely an ICP can occur in early pregnancy (first trimester), which calls for close monitoring. The risk of serious adverse fetal outcomes and spontaneous preterm delivery is proportional with increased levels of maternal serum bile acid.
PB  - MDPI
T2  - Medicina
T1  - Intrahepatic Cholestasis of Pregnancy: A Case Study of the Rare Onset in the First Trimester
VL  - 55
IS  - 8
DO  - 10.3390/medicina55080454
ER  - 

@article{
author = "Štulić, Miloš and Ćulafić, Đorđe and Boričić, Ivan and Stojković Lalošević, Milica and Pejić, Nina and Janković, Goran and Milovanović, Tamara and Ćulafić-Vojinović, Violeta and Vlaisavljević, Željko and Ćulafić, Milica",
year = "2019",
abstract = "Intrahepatic cholestasis of pregnancy (ICP) is a gestation-specific liver disorder, defined most often as the onset of pruritus, usually from the third trimester of pregnancy, associated with abnormal liver test results and/or increased total serum bile acids and spontaneous relief after delivery. The 21-year-old patient was admitted to our ward in the 11th week of pregnancy due to raised liver enzymes. The first onset of pruritus and jaundice appeared a month before hospitalization. Immunology tests and Toxoplasma gondii were negative. We excluded viral etiology, while alpha-1-antitrypsin, serum and urine copper levels, and thyroid hormones were within the reference values. The patient denied she had taken any medicines and herbal preparations before and during pregnancy. Total bile acids in the serum were significantly elevated (242 μmol/L). The abdominal ultrasound revealed a regular finding. Liver biopsy suggested a cholestatic liver disorder. After a presentation of all risks, the patient decided to stop the pregnancy. After a month, the hepatogram was within the reference values. Very rarely an ICP can occur in early pregnancy (first trimester), which calls for close monitoring. The risk of serious adverse fetal outcomes and spontaneous preterm delivery is proportional with increased levels of maternal serum bile acid.",
publisher = "MDPI",
journal = "Medicina",
title = "Intrahepatic Cholestasis of Pregnancy: A Case Study of the Rare Onset in the First Trimester",
volume = "55",
number = "8",
doi = "10.3390/medicina55080454"
}

Štulić, M., Ćulafić, Đ., Boričić, I., Stojković Lalošević, M., Pejić, N., Janković, G., Milovanović, T., Ćulafić-Vojinović, V., Vlaisavljević, Ž.,& Ćulafić, M.. (2019). Intrahepatic Cholestasis of Pregnancy: A Case Study of the Rare Onset in the First Trimester. in Medicina
MDPI., 55(8).
https://doi.org/10.3390/medicina55080454

Štulić M, Ćulafić Đ, Boričić I, Stojković Lalošević M, Pejić N, Janković G, Milovanović T, Ćulafić-Vojinović V, Vlaisavljević Ž, Ćulafić M. Intrahepatic Cholestasis of Pregnancy: A Case Study of the Rare Onset in the First Trimester. in Medicina. 2019;55(8).
doi:10.3390/medicina55080454 .

Štulić, Miloš, Ćulafić, Đorđe, Boričić, Ivan, Stojković Lalošević, Milica, Pejić, Nina, Janković, Goran, Milovanović, Tamara, Ćulafić-Vojinović, Violeta, Vlaisavljević, Željko, Ćulafić, Milica, "Intrahepatic Cholestasis of Pregnancy: A Case Study of the Rare Onset in the First Trimester" in Medicina, 55, no. 8 (2019),
https://doi.org/10.3390/medicina55080454 . .

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  - Stulić, Miloš
AU  - Ćulafić, Đorđe
AU  - Obrenović, Radmila
AU  - Janković, Goran
AU  - Alempijević, Tamara
AU  - Stojković-Lalošević, Milica
AU  - Dostanić, Nataša
AU  - Vezmar-Kovačević, Sandra
AU  - Ćulafić, Milica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3068
AB  - Background: Data suggest cystatin C (CysC) levels and hepatic artery resistive index (HARI) correspond to the progression of chronic liver disease. We aimed to evaluate the clinical significance of these parameters in assessment of fibrosis in patients with liver cirrhosis. Methods: The cross-sectional study included 63 patients with liver cirrhosis. A control group consisted of 30 age- and gender-matched healthy persons. Results: We confirmed significantly higher values of CysC in patients with cirrhosis compared to control group (p = 0.036). Average value of HARI in the examined group was increased (0.72 +/- 0.06) and there was the statistically significant difference compared to controls (0.66 +/- 0.03) (p  lt  0.001). We found statistically significant correlation between HARI and CysC in the study group. Analyzing the possibility of distinguishing healthy subjects from patients with fibrosis, we have found that the area under the curve is far greater in the HARI index than CysC. Comparison of CysC among Child-Pugh stages and correlation with a model for end-stage liver disease (MELD) score showed statistically significant results. Conclusion: We confirmed HARI is a more accurate parameter than CysC in discriminating healthy subjects from patients with fibrosis, while CysC could be a better indicator of the stage of liver cirrhosis.
PB  - MDPI, Basel
T2  - Medicina-Lithuania
T1  - The Clinical Importance of Cystatin C and Hepatic Artery Resistive Index in Liver Cirrhosis
VL  - 54
IS  - 3
DO  - 10.3390/medicina54030037
ER  - 

@article{
author = "Stulić, Miloš and Ćulafić, Đorđe and Obrenović, Radmila and Janković, Goran and Alempijević, Tamara and Stojković-Lalošević, Milica and Dostanić, Nataša and Vezmar-Kovačević, Sandra and Ćulafić, Milica",
year = "2018",
abstract = "Background: Data suggest cystatin C (CysC) levels and hepatic artery resistive index (HARI) correspond to the progression of chronic liver disease. We aimed to evaluate the clinical significance of these parameters in assessment of fibrosis in patients with liver cirrhosis. Methods: The cross-sectional study included 63 patients with liver cirrhosis. A control group consisted of 30 age- and gender-matched healthy persons. Results: We confirmed significantly higher values of CysC in patients with cirrhosis compared to control group (p = 0.036). Average value of HARI in the examined group was increased (0.72 +/- 0.06) and there was the statistically significant difference compared to controls (0.66 +/- 0.03) (p  lt  0.001). We found statistically significant correlation between HARI and CysC in the study group. Analyzing the possibility of distinguishing healthy subjects from patients with fibrosis, we have found that the area under the curve is far greater in the HARI index than CysC. Comparison of CysC among Child-Pugh stages and correlation with a model for end-stage liver disease (MELD) score showed statistically significant results. Conclusion: We confirmed HARI is a more accurate parameter than CysC in discriminating healthy subjects from patients with fibrosis, while CysC could be a better indicator of the stage of liver cirrhosis.",
publisher = "MDPI, Basel",
journal = "Medicina-Lithuania",
title = "The Clinical Importance of Cystatin C and Hepatic Artery Resistive Index in Liver Cirrhosis",
volume = "54",
number = "3",
doi = "10.3390/medicina54030037"
}

Stulić, M., Ćulafić, Đ., Obrenović, R., Janković, G., Alempijević, T., Stojković-Lalošević, M., Dostanić, N., Vezmar-Kovačević, S.,& Ćulafić, M.. (2018). The Clinical Importance of Cystatin C and Hepatic Artery Resistive Index in Liver Cirrhosis. in Medicina-Lithuania
MDPI, Basel., 54(3).
https://doi.org/10.3390/medicina54030037

Stulić M, Ćulafić Đ, Obrenović R, Janković G, Alempijević T, Stojković-Lalošević M, Dostanić N, Vezmar-Kovačević S, Ćulafić M. The Clinical Importance of Cystatin C and Hepatic Artery Resistive Index in Liver Cirrhosis. in Medicina-Lithuania. 2018;54(3).
doi:10.3390/medicina54030037 .

Stulić, Miloš, Ćulafić, Đorđe, Obrenović, Radmila, Janković, Goran, Alempijević, Tamara, Stojković-Lalošević, Milica, Dostanić, Nataša, Vezmar-Kovačević, Sandra, Ćulafić, Milica, "The Clinical Importance of Cystatin C and Hepatic Artery Resistive Index in Liver Cirrhosis" in Medicina-Lithuania, 54, no. 3 (2018),
https://doi.org/10.3390/medicina54030037 . .

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  - Rizvić, Eldina
AU  - Janković, Goran
AU  - Savić, Miroslav
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2993
AB  - Vasoconstrictive properties of sympathomimetic drugs are the basis of their widespread use as decongestants and possible source of adverse responses. Insufficiently substantiated practice of combining decongestants in some marketed preparations, such are those containing phenylephrine and lerimazoline, may affect the overall contractile activity, and thus their therapeutic utility. This study aimed to examine the interaction between lerimazoline and phenylephrine in isolated rat aortic rings, and also to assess the substrate of the obtained lerimazoline-induced attenuation of phenylephrine contraction. Namely, while lower concentrations of lerimazoline (10(-6) M and especially 10(-7) M) expectedly tended to potentiate the phenylephrine-induced contractions, lerimazoline in higher concentrations (10(-4) M and above) unexpectedly and profoundly depleted the phenylephrine concentration-response curve. Suppression of NO with NO synthase (NOS) inhibitor N-W-nitro-L-arginine methyl ester (L-NAME; 10(-4)M) or NO scavanger OHB12 (10(-3)M), as well as non-specific inhibition of K+-channels with tetraethylammonium (TEA; 10(-3) M), have reversed lerimazoline-induced relaxation of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin (10(-5) M) did not affect the interaction between two vasoconstrictors. At the receptor level, non-selective 5-HT receptor antagonist methiothepin reversed the attenuating effect of lerimazoline on phenylephrine contraction when applied at 3x10(-7) and 10(-6) M, but not at the highest concentration (10(-4) M). Neither the 5-HT1D-receptor selective antagonist BRL 15572 (10(-6) M) nor 5-HT7 receptor selective antagonist SB 269970 (10(-6) M) affected the lerimazoline-induced attenuation of phenylephrine activity. The mechanism of lerimazoline-induced suppression of phenylephrine contractions may involve potentiation of activity of NO and K+-channels and activation of some methiothepin-sensitive receptors, possibly of the 5-HT2B subtype.
PB  - Korean Journal Of Physiology & Pharmacology, Seoul
T2  - Korean Journal of Physiology & Pharmacology
T1  - Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant
VL  - 21
IS  - 4
SP  - 385
EP  - 395
DO  - 10.4196/kjpp.2017.21.4.385
ER  - 

@article{
author = "Rizvić, Eldina and Janković, Goran and Savić, Miroslav",
year = "2017",
abstract = "Vasoconstrictive properties of sympathomimetic drugs are the basis of their widespread use as decongestants and possible source of adverse responses. Insufficiently substantiated practice of combining decongestants in some marketed preparations, such are those containing phenylephrine and lerimazoline, may affect the overall contractile activity, and thus their therapeutic utility. This study aimed to examine the interaction between lerimazoline and phenylephrine in isolated rat aortic rings, and also to assess the substrate of the obtained lerimazoline-induced attenuation of phenylephrine contraction. Namely, while lower concentrations of lerimazoline (10(-6) M and especially 10(-7) M) expectedly tended to potentiate the phenylephrine-induced contractions, lerimazoline in higher concentrations (10(-4) M and above) unexpectedly and profoundly depleted the phenylephrine concentration-response curve. Suppression of NO with NO synthase (NOS) inhibitor N-W-nitro-L-arginine methyl ester (L-NAME; 10(-4)M) or NO scavanger OHB12 (10(-3)M), as well as non-specific inhibition of K+-channels with tetraethylammonium (TEA; 10(-3) M), have reversed lerimazoline-induced relaxation of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin (10(-5) M) did not affect the interaction between two vasoconstrictors. At the receptor level, non-selective 5-HT receptor antagonist methiothepin reversed the attenuating effect of lerimazoline on phenylephrine contraction when applied at 3x10(-7) and 10(-6) M, but not at the highest concentration (10(-4) M). Neither the 5-HT1D-receptor selective antagonist BRL 15572 (10(-6) M) nor 5-HT7 receptor selective antagonist SB 269970 (10(-6) M) affected the lerimazoline-induced attenuation of phenylephrine activity. The mechanism of lerimazoline-induced suppression of phenylephrine contractions may involve potentiation of activity of NO and K+-channels and activation of some methiothepin-sensitive receptors, possibly of the 5-HT2B subtype.",
publisher = "Korean Journal Of Physiology & Pharmacology, Seoul",
journal = "Korean Journal of Physiology & Pharmacology",
title = "Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant",
volume = "21",
number = "4",
pages = "385-395",
doi = "10.4196/kjpp.2017.21.4.385"
}

Rizvić, E., Janković, G.,& Savić, M.. (2017). Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant. in Korean Journal of Physiology & Pharmacology
Korean Journal Of Physiology & Pharmacology, Seoul., 21(4), 385-395.
https://doi.org/10.4196/kjpp.2017.21.4.385

Rizvić E, Janković G, Savić M. Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant. in Korean Journal of Physiology & Pharmacology. 2017;21(4):385-395.
doi:10.4196/kjpp.2017.21.4.385 .

Rizvić, Eldina, Janković, Goran, Savić, Miroslav, "Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant" in Korean Journal of Physiology & Pharmacology, 21, no. 4 (2017):385-395,
https://doi.org/10.4196/kjpp.2017.21.4.385 . .

TY  - JOUR
AU  - Rizvić, Eldina
AU  - Janković, Goran
AU  - Kostić-Rajacić, Sladana
AU  - Savić, Miroslav
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2790
AB  - Lerimazoline is a sympathomimetic drug that belongs to the imidazoline class of compounds, and is used as a nasal decongestant. Studies on lerimazoline are rare, and its pharmacological profile is not completely understood. Here, we analyzed the affinity of lerimazoline for dopamine receptor D2, serotonin 5-HT1A and 5-HT2A receptors and alpha(1)-adrenoceptor, and investigated lerimazoline contractile effects in isolated rat thoracic aorta. We also determined the effect of several antagonists on the contractile response to lerimazoline, including prazosin (alpha(1)-adrenoceptor antagonist), RX 821002 and rauwolscine (alpha(2)-adrenoceptor antagonists), JP 1302 (alpha(2C)-adrenoceptor antagonist), methiothepin (non-selective 5-HT receptor antagonist), SB 224289 (5-HT1B receptor antagonist), BRL 15572 (5-HT1D receptor antagonist), and ketanserin (5-HT2A receptor antagonist). Lerimazoline displayed high affinity for the 5-HT1A receptor (Ki = 162.5 nM), similar to the previously reported affinity for the 5-HT1D receptor. Binding affinity estimates (Ki) for alpha(1), 5-HT2A, and D-2 receptors were 6656, 4202 and 3437.5 nM, respectively (the literature reported Ki for 5-HT1B receptor is 3480 nM). Lerimazoline caused concentration-dependent contractions in 70% of preparations, varying in the range between 40% and 55% of the maximal contraction elicited by phenylephrine. While prazosin reduced the maximum contractile response to lerimazoline, rauwolscine showed a non-significant trend in reduction of the response. Both ketanserin (10 nM and 1 mu M) and methiothepin strongly suppressed the maximum response to lerimazoline. Overall, our results suggest that 5-HT2A and, less distinctly, alpha(1)-adrenergic receptors are involved in the lerimazoline-induced contractions, which makes lerimazoline an "atypical" decongestant.
PB  - Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, Cekalusa
T2  - Bosnian Journal of Basic Medical Sciences
T1  - Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors
VL  - 17
IS  - 3
SP  - 194
EP  - 202
DO  - 10.17305/bjbms.2017.2071
ER  - 

@article{
author = "Rizvić, Eldina and Janković, Goran and Kostić-Rajacić, Sladana and Savić, Miroslav",
year = "2017",
abstract = "Lerimazoline is a sympathomimetic drug that belongs to the imidazoline class of compounds, and is used as a nasal decongestant. Studies on lerimazoline are rare, and its pharmacological profile is not completely understood. Here, we analyzed the affinity of lerimazoline for dopamine receptor D2, serotonin 5-HT1A and 5-HT2A receptors and alpha(1)-adrenoceptor, and investigated lerimazoline contractile effects in isolated rat thoracic aorta. We also determined the effect of several antagonists on the contractile response to lerimazoline, including prazosin (alpha(1)-adrenoceptor antagonist), RX 821002 and rauwolscine (alpha(2)-adrenoceptor antagonists), JP 1302 (alpha(2C)-adrenoceptor antagonist), methiothepin (non-selective 5-HT receptor antagonist), SB 224289 (5-HT1B receptor antagonist), BRL 15572 (5-HT1D receptor antagonist), and ketanserin (5-HT2A receptor antagonist). Lerimazoline displayed high affinity for the 5-HT1A receptor (Ki = 162.5 nM), similar to the previously reported affinity for the 5-HT1D receptor. Binding affinity estimates (Ki) for alpha(1), 5-HT2A, and D-2 receptors were 6656, 4202 and 3437.5 nM, respectively (the literature reported Ki for 5-HT1B receptor is 3480 nM). Lerimazoline caused concentration-dependent contractions in 70% of preparations, varying in the range between 40% and 55% of the maximal contraction elicited by phenylephrine. While prazosin reduced the maximum contractile response to lerimazoline, rauwolscine showed a non-significant trend in reduction of the response. Both ketanserin (10 nM and 1 mu M) and methiothepin strongly suppressed the maximum response to lerimazoline. Overall, our results suggest that 5-HT2A and, less distinctly, alpha(1)-adrenergic receptors are involved in the lerimazoline-induced contractions, which makes lerimazoline an "atypical" decongestant.",
publisher = "Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, Cekalusa",
journal = "Bosnian Journal of Basic Medical Sciences",
title = "Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors",
volume = "17",
number = "3",
pages = "194-202",
doi = "10.17305/bjbms.2017.2071"
}

Rizvić, E., Janković, G., Kostić-Rajacić, S.,& Savić, M.. (2017). Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors. in Bosnian Journal of Basic Medical Sciences
Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, Cekalusa., 17(3), 194-202.
https://doi.org/10.17305/bjbms.2017.2071

Rizvić E, Janković G, Kostić-Rajacić S, Savić M. Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors. in Bosnian Journal of Basic Medical Sciences. 2017;17(3):194-202.
doi:10.17305/bjbms.2017.2071 .

Rizvić, Eldina, Janković, Goran, Kostić-Rajacić, Sladana, Savić, Miroslav, "Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors" in Bosnian Journal of Basic Medical Sciences, 17, no. 3 (2017):194-202,
https://doi.org/10.17305/bjbms.2017.2071 . .

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  - Todorović, Vanja
AU  - Radojčić-Redovniković, Ivana
AU  - Todorović, Zoran B.
AU  - Janković, Goran
AU  - Dodevska, Margarita
AU  - Šobajić, Slađana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2459
AB  - Different kinds of chocolates produced in Serbia were analyzed regarding total polyphenol, flavonoid and proanthocyanidin content using spectrophotometric methods. Flavan-3ols and methylxanthines in all samples were determined with RP-HPLC. DPPH, FRAP, ABTS and ORAC assays were applied for measuring antioxidant capacity. The average of all four antioxidant tests for each cocoa product was used for calculating antioxidant potency composite index (ACI). Obtained results for all four assays have shown that antioxidant capacity of analyzed chocolate/cocoa extracts followed cocoa, polyphenol, flavonoid, and proanthocyanidin contents. Although the addition of raspberries to dark chocolates had no significant influence on their total polyphenol, flavonoid and proanthocyanidin contents, statistical analysis showed that there was significant increase in the antioxidant capacity of dark chocolates with raspberry compared to plain dark chocolates (p = 0.007). Overall range for theobromine content varied from 5.5 to 22.3 mg/g depending on the product type, while the content of caffeine was 13-30 times lower in all analyzed cocoa products. In addition, correlation between antioxidant potency composite index and declared percentage of cocoa was high (R-2 = 0.798,p  lt  0.05) and indicated that declared cocoa content was a reliable indication for antioxidant capacity of chocolates produced in Serbia.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Journal of Food Composition and Analysis
T1  - Polyphenols, methylxanthines, and antioxidant capacity of chocolates produced in Serbia
VL  - 41
SP  - 137
EP  - 143
DO  - 10.1016/j.jfca.2015.01.018
ER  - 

@article{
author = "Todorović, Vanja and Radojčić-Redovniković, Ivana and Todorović, Zoran B. and Janković, Goran and Dodevska, Margarita and Šobajić, Slađana",
year = "2015",
abstract = "Different kinds of chocolates produced in Serbia were analyzed regarding total polyphenol, flavonoid and proanthocyanidin content using spectrophotometric methods. Flavan-3ols and methylxanthines in all samples were determined with RP-HPLC. DPPH, FRAP, ABTS and ORAC assays were applied for measuring antioxidant capacity. The average of all four antioxidant tests for each cocoa product was used for calculating antioxidant potency composite index (ACI). Obtained results for all four assays have shown that antioxidant capacity of analyzed chocolate/cocoa extracts followed cocoa, polyphenol, flavonoid, and proanthocyanidin contents. Although the addition of raspberries to dark chocolates had no significant influence on their total polyphenol, flavonoid and proanthocyanidin contents, statistical analysis showed that there was significant increase in the antioxidant capacity of dark chocolates with raspberry compared to plain dark chocolates (p = 0.007). Overall range for theobromine content varied from 5.5 to 22.3 mg/g depending on the product type, while the content of caffeine was 13-30 times lower in all analyzed cocoa products. In addition, correlation between antioxidant potency composite index and declared percentage of cocoa was high (R-2 = 0.798,p  lt  0.05) and indicated that declared cocoa content was a reliable indication for antioxidant capacity of chocolates produced in Serbia.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Journal of Food Composition and Analysis",
title = "Polyphenols, methylxanthines, and antioxidant capacity of chocolates produced in Serbia",
volume = "41",
pages = "137-143",
doi = "10.1016/j.jfca.2015.01.018"
}

Todorović, V., Radojčić-Redovniković, I., Todorović, Z. B., Janković, G., Dodevska, M.,& Šobajić, S.. (2015). Polyphenols, methylxanthines, and antioxidant capacity of chocolates produced in Serbia. in Journal of Food Composition and Analysis
Academic Press Inc Elsevier Science, San Diego., 41, 137-143.
https://doi.org/10.1016/j.jfca.2015.01.018

Todorović V, Radojčić-Redovniković I, Todorović ZB, Janković G, Dodevska M, Šobajić S. Polyphenols, methylxanthines, and antioxidant capacity of chocolates produced in Serbia. in Journal of Food Composition and Analysis. 2015;41:137-143.
doi:10.1016/j.jfca.2015.01.018 .

Todorović, Vanja, Radojčić-Redovniković, Ivana, Todorović, Zoran B., Janković, Goran, Dodevska, Margarita, Šobajić, Slađana, "Polyphenols, methylxanthines, and antioxidant capacity of chocolates produced in Serbia" in Journal of Food Composition and Analysis, 41 (2015):137-143,
https://doi.org/10.1016/j.jfca.2015.01.018 . .

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  - 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  - Vranić, Aleksandra
AU  - Janković, Goran
AU  - Stojanović, Ivan
AU  - Milojević, Predrag
AU  - Ugrešić, Nenad
AU  - Kanjuh, Vladimir
AU  - Yang, Qin
AU  - Guo-Wei, H.
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2072
PB  - Elsevier Ireland Ltd, Clare
C3  - Atherosclerosis
T1  - Cardioprotective effect of (-) epicatechin
VL  - 235
IS  - 2
SP  - e111
EP  - e111
DO  - 10.1016/j.atherosclerosis.2014.05.300
ER  - 

@conference{
author = "Novaković, Aleksandra and Vranić, Aleksandra and Janković, Goran and Stojanović, Ivan and Milojević, Predrag and Ugrešić, Nenad and Kanjuh, Vladimir and Yang, Qin and Guo-Wei, H.",
year = "2014",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Atherosclerosis",
title = "Cardioprotective effect of (-) epicatechin",
volume = "235",
number = "2",
pages = "e111-e111",
doi = "10.1016/j.atherosclerosis.2014.05.300"
}

Novaković, A., Vranić, A., Janković, G., Stojanović, I., Milojević, P., Ugrešić, N., Kanjuh, V., Yang, Q.,& Guo-Wei, H.. (2014). Cardioprotective effect of (-) epicatechin. in Atherosclerosis
Elsevier Ireland Ltd, Clare., 235(2), e111-e111.
https://doi.org/10.1016/j.atherosclerosis.2014.05.300

Novaković A, Vranić A, Janković G, Stojanović I, Milojević P, Ugrešić N, Kanjuh V, Yang Q, Guo-Wei H. Cardioprotective effect of (-) epicatechin. in Atherosclerosis. 2014;235(2):e111-e111.
doi:10.1016/j.atherosclerosis.2014.05.300 .

Novaković, Aleksandra, Vranić, Aleksandra, Janković, Goran, Stojanović, Ivan, Milojević, Predrag, Ugrešić, Nenad, Kanjuh, Vladimir, Yang, Qin, Guo-Wei, H., "Cardioprotective effect of (-) epicatechin" in Atherosclerosis, 235, no. 2 (2014):e111-e111,
https://doi.org/10.1016/j.atherosclerosis.2014.05.300 . .