Škrbić, Ranko

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  • Škrbić, Ranko (3)
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Author's Bibliography

Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta

Gajić Bojić, Milica; Treven, Marco; Pandey, Kamal P; Tiruveedhula, Phani Babu V V N; Santrač, Anja; Đukanović, Đorđe; Vojinović, Nataša; Amidžić, Ljiljana; Škrbić, Ranko; Scholze, Petra; Ernst, Margot; Cook, James M; Savić, Miroslav

(Canadian Science Publishing, 2024)

TY  - JOUR
AU  - Gajić Bojić, Milica
AU  - Treven, Marco
AU  - Pandey, Kamal P
AU  - Tiruveedhula, Phani Babu V V N
AU  - Santrač, Anja
AU  - Đukanović, Đorđe
AU  - Vojinović, Nataša
AU  - Amidžić, Ljiljana
AU  - Škrbić, Ranko
AU  - Scholze, Petra
AU  - Ernst, Margot
AU  - Cook, James M
AU  - Savić, Miroslav
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5619
AB  - Hypotensive influences of benzodiazepines and other GABAA receptor ligands, recognized in clinical practice, seem to stem from the existence of “vascular” GABAA receptors in peripheral blood vessels, besides any mechanisms in the central and peripheral nervous systems. We aimed to further elucidate the vasodilatatory effects of ligands acting through GABAA receptors. Using immunohistochemistry, the rat aortic smooth muscle layer was found to express GABAA γ 2 and α1-5 subunit proteins. To confirm the role of “vascular” GABAA receptors, we investigated the vascular effects of standard benzodiazepines, mida-zolam, and flumazenil, as well as the novel compound MP-III-058. Using two-electrode voltage clamp electrophysiology and radioligand binding assays, MP-III-058 was found to have modest binding but substantial functional selectivity for α5β3γ 2 over other αxβ3γ 2 GABAA receptors. Tissue bath assays revealed comparable vasodilatory effects of MP-III-058 and midazo-lam, both of which at 100 μmol/L concentrations had efficacy similar to prazosin. Flumazenil exhibited weak vasoactivity per se, but significantly prevented the relaxant effects of midazolam and MP-III-058. These studies indicate the existence of functional GABAA receptors in the rat aorta, where ligands exert vasodilatory effects by positive modulation of the benzodiazepine binding site, suggesting the potential for further quest for leads with optimized pharmacokinetic properties as prospective adjuvant vasodilators.
PB  - Canadian Science Publishing
T2  - Canadian  Journal of Physiology and  Pharmacology
T1  - Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta
VL  - 102
IS  - 3
SP  - 206
EP  - 217
DO  - 10.1139/cjpp-2023-0285
ER  - 
@article{
author = "Gajić Bojić, Milica and Treven, Marco and Pandey, Kamal P and Tiruveedhula, Phani Babu V V N and Santrač, Anja and Đukanović, Đorđe and Vojinović, Nataša and Amidžić, Ljiljana and Škrbić, Ranko and Scholze, Petra and Ernst, Margot and Cook, James M and Savić, Miroslav",
year = "2024",
abstract = "Hypotensive influences of benzodiazepines and other GABAA receptor ligands, recognized in clinical practice, seem to stem from the existence of “vascular” GABAA receptors in peripheral blood vessels, besides any mechanisms in the central and peripheral nervous systems. We aimed to further elucidate the vasodilatatory effects of ligands acting through GABAA receptors. Using immunohistochemistry, the rat aortic smooth muscle layer was found to express GABAA γ 2 and α1-5 subunit proteins. To confirm the role of “vascular” GABAA receptors, we investigated the vascular effects of standard benzodiazepines, mida-zolam, and flumazenil, as well as the novel compound MP-III-058. Using two-electrode voltage clamp electrophysiology and radioligand binding assays, MP-III-058 was found to have modest binding but substantial functional selectivity for α5β3γ 2 over other αxβ3γ 2 GABAA receptors. Tissue bath assays revealed comparable vasodilatory effects of MP-III-058 and midazo-lam, both of which at 100 μmol/L concentrations had efficacy similar to prazosin. Flumazenil exhibited weak vasoactivity per se, but significantly prevented the relaxant effects of midazolam and MP-III-058. These studies indicate the existence of functional GABAA receptors in the rat aorta, where ligands exert vasodilatory effects by positive modulation of the benzodiazepine binding site, suggesting the potential for further quest for leads with optimized pharmacokinetic properties as prospective adjuvant vasodilators.",
publisher = "Canadian Science Publishing",
journal = "Canadian  Journal of Physiology and  Pharmacology",
title = "Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta",
volume = "102",
number = "3",
pages = "206-217",
doi = "10.1139/cjpp-2023-0285"
}
Gajić Bojić, M., Treven, M., Pandey, K. P., Tiruveedhula, P. B. V. V. N., Santrač, A., Đukanović, Đ., Vojinović, N., Amidžić, L., Škrbić, R., Scholze, P., Ernst, M., Cook, J. M.,& Savić, M.. (2024). Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta. in Canadian  Journal of Physiology and  Pharmacology
Canadian Science Publishing., 102(3), 206-217.
https://doi.org/10.1139/cjpp-2023-0285
Gajić Bojić M, Treven M, Pandey KP, Tiruveedhula PBVVN, Santrač A, Đukanović Đ, Vojinović N, Amidžić L, Škrbić R, Scholze P, Ernst M, Cook JM, Savić M. Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta. in Canadian  Journal of Physiology and  Pharmacology. 2024;102(3):206-217.
doi:10.1139/cjpp-2023-0285 .
Gajić Bojić, Milica, Treven, Marco, Pandey, Kamal P, Tiruveedhula, Phani Babu V V N, Santrač, Anja, Đukanović, Đorđe, Vojinović, Nataša, Amidžić, Ljiljana, Škrbić, Ranko, Scholze, Petra, Ernst, Margot, Cook, James M, Savić, Miroslav, "Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta" in Canadian  Journal of Physiology and  Pharmacology, 102, no. 3 (2024):206-217,
https://doi.org/10.1139/cjpp-2023-0285 . .

In Silico and In Vitro Studies of Alchemilla viridiflora Rothm-Polyphenols' Potential for Inhibition of SARS-CoV-2 Internalization

Suručić, Relja; Radović-Selgrad, Jelena; Kundaković-Vasović, Tatjana; Lazović, Vesna; Travar, Maja; Suručić, Ljiljana; Škrbić, Ranko

(MDPI, 2022)

TY  - JOUR
AU  - Suručić, Relja
AU  - Radović-Selgrad, Jelena
AU  - Kundaković-Vasović, Tatjana
AU  - Lazović, Vesna
AU  - Travar, Maja
AU  - Suručić, Ljiljana
AU  - Škrbić, Ranko
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4261
AB  - Since the outbreak of the COVID-19 pandemic, it has been obvious that virus infection poses
a serious threat to human health on a global scale. Certain plants, particularly those rich in polyphe-
nols, have been found to be effective antiviral agents. The effectiveness of Alchemilla viridiflora Rothm.
(Rosaceae) methanol extract to prevent contact between virus spike (S)-glycoprotein and angiotensin-
converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) receptors was investigated. In vitro results
revealed that the tested samples inhibited 50% of virus-receptor binding interactions in doses of
0.18 and 0.22 mg/mL for NRP1 and ACE2, respectively. Molecular docking studies revealed that the
compounds from A. viridiflora ellagitannins class had a higher affinity for binding with S-glycoprotein
whilst flavonoid compounds more significantly interacted with the NRP1 receptor. Quercetin
3-(6”-ferulylglucoside) and pentagalloylglucose were two compounds with the highest exhibited
interfering potential for selected target receptors, with binding energies of −8.035 (S-glycoprotein)
and −7.685 kcal/mol (NRP1), respectively. Furthermore, computational studies on other SARS-CoV-2
strains resulting from mutations in the original wild strain (V483A, N501Y-K417N-E484K, N501Y,
N439K, L452R-T478K, K417N, G476S, F456L, E484K) revealed that virus internalization activity was
maintained, but with different single compound contributions.
PB  - MDPI
T2  - Molecules
T1  - In Silico and In Vitro Studies of Alchemilla viridiflora Rothm-Polyphenols' Potential for Inhibition of SARS-CoV-2 Internalization
VL  - 27
IS  - 16
DO  - 10.3390/molecules27165174
ER  - 
@article{
author = "Suručić, Relja and Radović-Selgrad, Jelena and Kundaković-Vasović, Tatjana and Lazović, Vesna and Travar, Maja and Suručić, Ljiljana and Škrbić, Ranko",
year = "2022",
abstract = "Since the outbreak of the COVID-19 pandemic, it has been obvious that virus infection poses
a serious threat to human health on a global scale. Certain plants, particularly those rich in polyphe-
nols, have been found to be effective antiviral agents. The effectiveness of Alchemilla viridiflora Rothm.
(Rosaceae) methanol extract to prevent contact between virus spike (S)-glycoprotein and angiotensin-
converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) receptors was investigated. In vitro results
revealed that the tested samples inhibited 50% of virus-receptor binding interactions in doses of
0.18 and 0.22 mg/mL for NRP1 and ACE2, respectively. Molecular docking studies revealed that the
compounds from A. viridiflora ellagitannins class had a higher affinity for binding with S-glycoprotein
whilst flavonoid compounds more significantly interacted with the NRP1 receptor. Quercetin
3-(6”-ferulylglucoside) and pentagalloylglucose were two compounds with the highest exhibited
interfering potential for selected target receptors, with binding energies of −8.035 (S-glycoprotein)
and −7.685 kcal/mol (NRP1), respectively. Furthermore, computational studies on other SARS-CoV-2
strains resulting from mutations in the original wild strain (V483A, N501Y-K417N-E484K, N501Y,
N439K, L452R-T478K, K417N, G476S, F456L, E484K) revealed that virus internalization activity was
maintained, but with different single compound contributions.",
publisher = "MDPI",
journal = "Molecules",
title = "In Silico and In Vitro Studies of Alchemilla viridiflora Rothm-Polyphenols' Potential for Inhibition of SARS-CoV-2 Internalization",
volume = "27",
number = "16",
doi = "10.3390/molecules27165174"
}
Suručić, R., Radović-Selgrad, J., Kundaković-Vasović, T., Lazović, V., Travar, M., Suručić, L.,& Škrbić, R.. (2022). In Silico and In Vitro Studies of Alchemilla viridiflora Rothm-Polyphenols' Potential for Inhibition of SARS-CoV-2 Internalization. in Molecules
MDPI., 27(16).
https://doi.org/10.3390/molecules27165174
Suručić R, Radović-Selgrad J, Kundaković-Vasović T, Lazović V, Travar M, Suručić L, Škrbić R. In Silico and In Vitro Studies of Alchemilla viridiflora Rothm-Polyphenols' Potential for Inhibition of SARS-CoV-2 Internalization. in Molecules. 2022;27(16).
doi:10.3390/molecules27165174 .
Suručić, Relja, Radović-Selgrad, Jelena, Kundaković-Vasović, Tatjana, Lazović, Vesna, Travar, Maja, Suručić, Ljiljana, Škrbić, Ranko, "In Silico and In Vitro Studies of Alchemilla viridiflora Rothm-Polyphenols' Potential for Inhibition of SARS-CoV-2 Internalization" in Molecules, 27, no. 16 (2022),
https://doi.org/10.3390/molecules27165174 . .
4
3

Pharmacists’ clinical knowledge and practice in the safe use of contraceptives: real knowledge vs. self-perception and the implications

Golić-Jelić, Ana; Tasić, Ljiljana; Škrbić, Ranko; Marinković, Valentina; Stoisavljević Šatara, Svjetlana; Stojaković, Nataša; Marković Peković, Vanda; Godman, Brian

(BioMed Central Ltd, 2021)

TY  - JOUR
AU  - Golić-Jelić, Ana
AU  - Tasić, Ljiljana
AU  - Škrbić, Ranko
AU  - Marinković, Valentina
AU  - Stoisavljević Šatara, Svjetlana
AU  - Stojaković, Nataša
AU  - Marković Peković, Vanda
AU  - Godman, Brian
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3937
AB  - Background: Pharmacists are often the first healthcare professionals that patients contact with their illnesses and requests for medical information, which is enhanced following the recent COVID-19 pandemic. Community pharmacists are expected and required to possess a broad spectrum of knowledge and skills. Self-assessment of these competencies is needed for their self-improvement. Purpose of the study: To assess pharmacists’ clinical knowledge and practice in the safe use of contraceptives, and to compare the scores obtained by external observation with pharmacists’ self-assessment of their knowledge as well as investigate the significance of preceptorship experiences. Contraceptives was chosen as the subject area in view of high rates of abortions as a means of contraception in Bosnia and Herzegovina. Methods: A questionnaire approach was used. The questionnaire included the following: the first domain contained two case scenarios (safe use of contraceptives), which evaluated clinical knowledge, a second domain in which pharmacists self-assessed their knowledge to resolve cases from the first domain and a third domain that measured the demographics of pharmacists (including experience in preceptorship). Dispensing practice was evaluated in the second domain. The questionnaires were distributed to a convenient sample of 100 pharmacists at the Annual Meeting of Bosnia and Herzegovina Pharmacists. The results were presented as counts (%). The groups (preceptors and non-preceptors) were compared using Mann-Whitney U test, paired assessments were analyzed by Wilcoxon signed-rank test and Spearman’s correlation was used to assess the correlation between variables. Results: Of the 100 pharmacists invited to participate, 84 completed the questionnaire (84 % response rate). There was no agreement between pharmacists’ real knowledge (average score - case 1: 2.71, case 2: 3.3) and their self-assessment (average score - case 1: 3.77, case 2: 3.91). There was no statistically significant difference in the actual knowledge of pharmacists (experienced/non-experienced in precepting), while the difference in the self-assessment was significant between these two groups. Conclusion: Pharmacists appear to overrate themselves, which leads to self-enhancement bias, in which the experience in precepting has some influence. Pharmacists’ capability in performing an objective self-assessment of their clinical knowledge needs to be carefully studied in the future to fully benefit patients.
PB  - BioMed Central Ltd
T2  - BMC Medical Education
T1  - Pharmacists’ clinical knowledge and practice in the safe use of contraceptives: real knowledge vs. self-perception and the implications
VL  - 21
IS  - 1
DO  - 10.1186/s12909-021-02864-9
ER  - 
@article{
author = "Golić-Jelić, Ana and Tasić, Ljiljana and Škrbić, Ranko and Marinković, Valentina and Stoisavljević Šatara, Svjetlana and Stojaković, Nataša and Marković Peković, Vanda and Godman, Brian",
year = "2021",
abstract = "Background: Pharmacists are often the first healthcare professionals that patients contact with their illnesses and requests for medical information, which is enhanced following the recent COVID-19 pandemic. Community pharmacists are expected and required to possess a broad spectrum of knowledge and skills. Self-assessment of these competencies is needed for their self-improvement. Purpose of the study: To assess pharmacists’ clinical knowledge and practice in the safe use of contraceptives, and to compare the scores obtained by external observation with pharmacists’ self-assessment of their knowledge as well as investigate the significance of preceptorship experiences. Contraceptives was chosen as the subject area in view of high rates of abortions as a means of contraception in Bosnia and Herzegovina. Methods: A questionnaire approach was used. The questionnaire included the following: the first domain contained two case scenarios (safe use of contraceptives), which evaluated clinical knowledge, a second domain in which pharmacists self-assessed their knowledge to resolve cases from the first domain and a third domain that measured the demographics of pharmacists (including experience in preceptorship). Dispensing practice was evaluated in the second domain. The questionnaires were distributed to a convenient sample of 100 pharmacists at the Annual Meeting of Bosnia and Herzegovina Pharmacists. The results were presented as counts (%). The groups (preceptors and non-preceptors) were compared using Mann-Whitney U test, paired assessments were analyzed by Wilcoxon signed-rank test and Spearman’s correlation was used to assess the correlation between variables. Results: Of the 100 pharmacists invited to participate, 84 completed the questionnaire (84 % response rate). There was no agreement between pharmacists’ real knowledge (average score - case 1: 2.71, case 2: 3.3) and their self-assessment (average score - case 1: 3.77, case 2: 3.91). There was no statistically significant difference in the actual knowledge of pharmacists (experienced/non-experienced in precepting), while the difference in the self-assessment was significant between these two groups. Conclusion: Pharmacists appear to overrate themselves, which leads to self-enhancement bias, in which the experience in precepting has some influence. Pharmacists’ capability in performing an objective self-assessment of their clinical knowledge needs to be carefully studied in the future to fully benefit patients.",
publisher = "BioMed Central Ltd",
journal = "BMC Medical Education",
title = "Pharmacists’ clinical knowledge and practice in the safe use of contraceptives: real knowledge vs. self-perception and the implications",
volume = "21",
number = "1",
doi = "10.1186/s12909-021-02864-9"
}
Golić-Jelić, A., Tasić, L., Škrbić, R., Marinković, V., Stoisavljević Šatara, S., Stojaković, N., Marković Peković, V.,& Godman, B.. (2021). Pharmacists’ clinical knowledge and practice in the safe use of contraceptives: real knowledge vs. self-perception and the implications. in BMC Medical Education
BioMed Central Ltd., 21(1).
https://doi.org/10.1186/s12909-021-02864-9
Golić-Jelić A, Tasić L, Škrbić R, Marinković V, Stoisavljević Šatara S, Stojaković N, Marković Peković V, Godman B. Pharmacists’ clinical knowledge and practice in the safe use of contraceptives: real knowledge vs. self-perception and the implications. in BMC Medical Education. 2021;21(1).
doi:10.1186/s12909-021-02864-9 .
Golić-Jelić, Ana, Tasić, Ljiljana, Škrbić, Ranko, Marinković, Valentina, Stoisavljević Šatara, Svjetlana, Stojaković, Nataša, Marković Peković, Vanda, Godman, Brian, "Pharmacists’ clinical knowledge and practice in the safe use of contraceptives: real knowledge vs. self-perception and the implications" in BMC Medical Education, 21, no. 1 (2021),
https://doi.org/10.1186/s12909-021-02864-9 . .
1