TY  - THES
AU  - Milutinović, Violeta
PY  - 2021
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=8442
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:24744/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=49042953
UR  - https://nardus.mpn.gov.rs/handle/123456789/18845
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4039
AB  - hibridogenih).Semipreparativnim LC-MS metodama, iz MeOH ekstrakta cvasti H. calophyllum izolovana sučetiri seskviterpenska laktona (krepizid E i tri nova jedinjenja: 8-epi-ikserisamin A, kalofilamin A ikalofilamin B), a iz MeOH ekstrakta podzemnih organa H. scheppigianum pet fenolkarboksilnih(mono- ili di-O-kafeoilhina) kiselina (identifikacija na osnovu NMR i MS spektara).Ukupno četiri seskviterpenska laktona, sedam mono- ili di-O-kafeoilhina kiselina i 19flavonoida (luteolin, apigenin, diosmetin, 15 njihovih heterozida i heterozid kvercetina)kvantifikovani su u suvim MeOH ekstraktima ispitivanih podzemnih organa dve vrste i herbi 28vrsta LC-MS metodama, i pet triterpena (derivata ursana, oleana i lupana) u suvim CH2Cl2ekstraktima herbi 28 vrsta GC-FID-MS metodom (identifikacija pomoću standarda, NMR, MS i/iliUV spektara). Hemosistematski značaj jedinjenja identifikovanih u herbama 28 vrsta utvrđen jemultivarijantnim statističkim metodama (PCA, nMDS i UPGMA).Suvi MeOH ekstrakti herbi su in vitro pokazali značajan ukupni antioksidantni potencijal isposobnost neutralizacije slobodnih DPPH•, ABTS•+ i OH• radikala (28 vrsta) i inhibicijeacetilholinesteraze (27 vrsta) i butirilholinesteraze (7 vrsta). Među testiranih 12 jedinjenja, najboljuantiholinesteraznu aktivnost ispoljila su tri flavonoidna aglikona i 8-epi-ikserisamin A. Odabranisuvi MeOH i CH2Cl2 ekstrakti herbi šest vrsta pokazali su antimikrobnu aktivnost prema 18, a 8-epi-ikserisamin A i krepizid E prema 4 mikroorganizma. Isti odabrani izolati ispoljili sucitotoksični efekat prema tri, odnosno jednoj tumorskoj ćelijskoj liniji, uz zanemarljivu inhibicijurasta zdravih ćelija. Tri odabrana MeOH i CH2Cl2 ekstrakta su u modelu inflamacije šape pacovaizazvane karageninom pokazala antihiperalgezijsku, ali ne i antiedematoznu aktivnost; bezbednostprimene dva ekstrakta koji su ispoljili značajnu antihiperalgezijsku aktivnost pokazana je in vivorotarod i testom akutne toksičnosti.Ključne reči:
AB  - nonhybridogenousand 16 hybridogenous).Using semipreparative LC-MS methods, four sesquiterpene lactones (crepiside E and three newcompounds: 8-epiixerisamine A, calophyllamine A and calophyllamine B) were isolated from theMeOH extract of H. calophyllum flowering heads, and five phenolic (mono- or di-Ocaffeoylquinic)acids from the MeOH extract of H. scheppigianum underground parts(identification based on NMR and MS spectra).Total of four sesquiterpene lactones, seven mono- or di-O-caffeoylquinic acids and 19flavonoids (luteolin, apigenin, diosmetin, their 15 glycosides and one quercetin glycoside) werequantified in the dried MeOH extracts of the investigated underground parts of two species andherbs of 28 species, using LC-MS methods, and five triterpenes (ursane, oleane and lupanederivatives) in the dried CH2Cl2 extracts of the herbs of 28 species, using GC-FID-MS method(identification using standards, NMR, MS and/or UV spectra). Chemosystematic significance ofthe compounds identified in the herbs of 28 species was determined using multivariate statistics(PCA, nMDS and UPGMA).Dried MeOH herb extracts in vitro exhibited significant total antioxidant activity andscavenging of DPPH•, ABTS•+ and OH• radicals (28 species), as well as the ability to inhibitacetylcholinesterase (27 species) and butyrylcholinesterase (7 species). Among 12 testedcompounds, three flavonoid aglycones and 8-epiixerisamine A exhibited the highestanticholinesterase activity. Selected dried MeOH and CH2Cl2 herb extracts of six species showedantimicrobial activity against 18, whereas 8-epiixerisamine A and crepiside E against fourmicroorganisms. The same selected isolates exhibited cytotoxic activity against three and onecancer cell lines, respectively, with negligible inhibition of the normal cells growth. In thecarrageenan-induced localized inflammation model in rats, three selected MeOH and CH2Cl2extracts exhibited antihyperalgesic, but not antiedematous activity; safety of the oral administrationof two extracts that exhibited significant antihyperalgesic activity was demonstrated in vivo inrotarod test and acute oral toxicity study.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Ispitivanje sekundarnih metabolita i farmakološke aktivnosti odabranih vrsta roda Hieracium L. (Asteraceae) sa Balkanskog poluostrva
UR  - https://hdl.handle.net/21.15107/rcub_nardus_18845
ER  - 

@phdthesis{
author = "Milutinović, Violeta",
year = "2021",
abstract = "hibridogenih).Semipreparativnim LC-MS metodama, iz MeOH ekstrakta cvasti H. calophyllum izolovana sučetiri seskviterpenska laktona (krepizid E i tri nova jedinjenja: 8-epi-ikserisamin A, kalofilamin A ikalofilamin B), a iz MeOH ekstrakta podzemnih organa H. scheppigianum pet fenolkarboksilnih(mono- ili di-O-kafeoilhina) kiselina (identifikacija na osnovu NMR i MS spektara).Ukupno četiri seskviterpenska laktona, sedam mono- ili di-O-kafeoilhina kiselina i 19flavonoida (luteolin, apigenin, diosmetin, 15 njihovih heterozida i heterozid kvercetina)kvantifikovani su u suvim MeOH ekstraktima ispitivanih podzemnih organa dve vrste i herbi 28vrsta LC-MS metodama, i pet triterpena (derivata ursana, oleana i lupana) u suvim CH2Cl2ekstraktima herbi 28 vrsta GC-FID-MS metodom (identifikacija pomoću standarda, NMR, MS i/iliUV spektara). Hemosistematski značaj jedinjenja identifikovanih u herbama 28 vrsta utvrđen jemultivarijantnim statističkim metodama (PCA, nMDS i UPGMA).Suvi MeOH ekstrakti herbi su in vitro pokazali značajan ukupni antioksidantni potencijal isposobnost neutralizacije slobodnih DPPH•, ABTS•+ i OH• radikala (28 vrsta) i inhibicijeacetilholinesteraze (27 vrsta) i butirilholinesteraze (7 vrsta). Među testiranih 12 jedinjenja, najboljuantiholinesteraznu aktivnost ispoljila su tri flavonoidna aglikona i 8-epi-ikserisamin A. Odabranisuvi MeOH i CH2Cl2 ekstrakti herbi šest vrsta pokazali su antimikrobnu aktivnost prema 18, a 8-epi-ikserisamin A i krepizid E prema 4 mikroorganizma. Isti odabrani izolati ispoljili sucitotoksični efekat prema tri, odnosno jednoj tumorskoj ćelijskoj liniji, uz zanemarljivu inhibicijurasta zdravih ćelija. Tri odabrana MeOH i CH2Cl2 ekstrakta su u modelu inflamacije šape pacovaizazvane karageninom pokazala antihiperalgezijsku, ali ne i antiedematoznu aktivnost; bezbednostprimene dva ekstrakta koji su ispoljili značajnu antihiperalgezijsku aktivnost pokazana je in vivorotarod i testom akutne toksičnosti.Ključne reči:, nonhybridogenousand 16 hybridogenous).Using semipreparative LC-MS methods, four sesquiterpene lactones (crepiside E and three newcompounds: 8-epiixerisamine A, calophyllamine A and calophyllamine B) were isolated from theMeOH extract of H. calophyllum flowering heads, and five phenolic (mono- or di-Ocaffeoylquinic)acids from the MeOH extract of H. scheppigianum underground parts(identification based on NMR and MS spectra).Total of four sesquiterpene lactones, seven mono- or di-O-caffeoylquinic acids and 19flavonoids (luteolin, apigenin, diosmetin, their 15 glycosides and one quercetin glycoside) werequantified in the dried MeOH extracts of the investigated underground parts of two species andherbs of 28 species, using LC-MS methods, and five triterpenes (ursane, oleane and lupanederivatives) in the dried CH2Cl2 extracts of the herbs of 28 species, using GC-FID-MS method(identification using standards, NMR, MS and/or UV spectra). Chemosystematic significance ofthe compounds identified in the herbs of 28 species was determined using multivariate statistics(PCA, nMDS and UPGMA).Dried MeOH herb extracts in vitro exhibited significant total antioxidant activity andscavenging of DPPH•, ABTS•+ and OH• radicals (28 species), as well as the ability to inhibitacetylcholinesterase (27 species) and butyrylcholinesterase (7 species). Among 12 testedcompounds, three flavonoid aglycones and 8-epiixerisamine A exhibited the highestanticholinesterase activity. Selected dried MeOH and CH2Cl2 herb extracts of six species showedantimicrobial activity against 18, whereas 8-epiixerisamine A and crepiside E against fourmicroorganisms. The same selected isolates exhibited cytotoxic activity against three and onecancer cell lines, respectively, with negligible inhibition of the normal cells growth. In thecarrageenan-induced localized inflammation model in rats, three selected MeOH and CH2Cl2extracts exhibited antihyperalgesic, but not antiedematous activity; safety of the oral administrationof two extracts that exhibited significant antihyperalgesic activity was demonstrated in vivo inrotarod test and acute oral toxicity study.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Ispitivanje sekundarnih metabolita i farmakološke aktivnosti odabranih vrsta roda Hieracium L. (Asteraceae) sa Balkanskog poluostrva",
url = "https://hdl.handle.net/21.15107/rcub_nardus_18845"
}

Milutinović, V.. (2021). Ispitivanje sekundarnih metabolita i farmakološke aktivnosti odabranih vrsta roda Hieracium L. (Asteraceae) sa Balkanskog poluostrva. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_18845

Milutinović V. Ispitivanje sekundarnih metabolita i farmakološke aktivnosti odabranih vrsta roda Hieracium L. (Asteraceae) sa Balkanskog poluostrva. in Универзитет у Београду. 2021;.
https://hdl.handle.net/21.15107/rcub_nardus_18845 .

Milutinović, Violeta, "Ispitivanje sekundarnih metabolita i farmakološke aktivnosti odabranih vrsta roda Hieracium L. (Asteraceae) sa Balkanskog poluostrva" in Универзитет у Београду (2021),
https://hdl.handle.net/21.15107/rcub_nardus_18845 .

TY  - JOUR
AU  - Milutinović, Violeta
AU  - Pecikoza, Uroš
AU  - Tomić, Maja
AU  - Stepanović-Petrović, Radica
AU  - Niketić, Marjan
AU  - Ušjak, Ljuboš
AU  - Petrović, Silvana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3641
AB  - Present study investigated triterpene profile, antihyperalgesic and antiedematous activities of Hieracium scheppigianum flowering aerial parts dichloromethane extract (SCH), and antihyperalgesic and antiedematous activities of previously chemically characterised polyphenol-rich H. glabratum and H. calophyllum flowering aerial parts methanol extracts (GLA and CAL, respectively). α- and β-Amyrin and their acetates, and lupeol acetate were identified and quantified in SCH by GC-FID and GC-MS. In carrageenan-induced localised inflammation model in rats, SCH and GLA (50–200 mg/kg, p.o.) produced significant and dose-dependent antihyperalgesic effect of 26.9%–56.2% (ED50=163.0 ± 26.5 mg/kg) and 25.3%–51.6% (ED50=211.6 ± 70.6 mg/kg), respectively, and CAL (200 mg/kg, p.o.) exhibited effect of 38.1%. Extracts did not significantly reduce paw edema. SCH and GLA, which demonstrated higher (over 50%) antihyperalgesic efficacy, were tested in a rotarod test (200 mg/kg, p.o.) and no alteration of motor coordination was observed. Also, acute administration of SCH and GLA in mice (2000 mg/kg, p.o.) caused neither mortality nor toxicity.
PB  - Taylor & Francis Ltd
T2  - Natural Product Research
T1  - Investigation of antihyperalgesic and antiedematous activities of three Hieracium species
VL  - 35
IS  - 23
SP  - 5384
EP  - 5388
DO  - 10.1080/14786419.2020.1768086
ER  - 

@article{
author = "Milutinović, Violeta and Pecikoza, Uroš and Tomić, Maja and Stepanović-Petrović, Radica and Niketić, Marjan and Ušjak, Ljuboš and Petrović, Silvana",
year = "2021",
abstract = "Present study investigated triterpene profile, antihyperalgesic and antiedematous activities of Hieracium scheppigianum flowering aerial parts dichloromethane extract (SCH), and antihyperalgesic and antiedematous activities of previously chemically characterised polyphenol-rich H. glabratum and H. calophyllum flowering aerial parts methanol extracts (GLA and CAL, respectively). α- and β-Amyrin and their acetates, and lupeol acetate were identified and quantified in SCH by GC-FID and GC-MS. In carrageenan-induced localised inflammation model in rats, SCH and GLA (50–200 mg/kg, p.o.) produced significant and dose-dependent antihyperalgesic effect of 26.9%–56.2% (ED50=163.0 ± 26.5 mg/kg) and 25.3%–51.6% (ED50=211.6 ± 70.6 mg/kg), respectively, and CAL (200 mg/kg, p.o.) exhibited effect of 38.1%. Extracts did not significantly reduce paw edema. SCH and GLA, which demonstrated higher (over 50%) antihyperalgesic efficacy, were tested in a rotarod test (200 mg/kg, p.o.) and no alteration of motor coordination was observed. Also, acute administration of SCH and GLA in mice (2000 mg/kg, p.o.) caused neither mortality nor toxicity.",
publisher = "Taylor & Francis Ltd",
journal = "Natural Product Research",
title = "Investigation of antihyperalgesic and antiedematous activities of three Hieracium species",
volume = "35",
number = "23",
pages = "5384-5388",
doi = "10.1080/14786419.2020.1768086"
}

Milutinović, V., Pecikoza, U., Tomić, M., Stepanović-Petrović, R., Niketić, M., Ušjak, L.,& Petrović, S.. (2021). Investigation of antihyperalgesic and antiedematous activities of three Hieracium species. in Natural Product Research
Taylor & Francis Ltd., 35(23), 5384-5388.
https://doi.org/10.1080/14786419.2020.1768086

Milutinović V, Pecikoza U, Tomić M, Stepanović-Petrović R, Niketić M, Ušjak L, Petrović S. Investigation of antihyperalgesic and antiedematous activities of three Hieracium species. in Natural Product Research. 2021;35(23):5384-5388.
doi:10.1080/14786419.2020.1768086 .

Milutinović, Violeta, Pecikoza, Uroš, Tomić, Maja, Stepanović-Petrović, Radica, Niketić, Marjan, Ušjak, Ljuboš, Petrović, Silvana, "Investigation of antihyperalgesic and antiedematous activities of three Hieracium species" in Natural Product Research, 35, no. 23 (2021):5384-5388,
https://doi.org/10.1080/14786419.2020.1768086 . .

TY  - THES
AU  - Pecikoza, Uroš
PY  - 2021
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=8244
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:23972/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=39014921
UR  - https://nardus.mpn.gov.rs/handle/123456789/18520
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4037
AB  - Bol je kompleksno senzorno iskustvo koje ima jasnu zaštitnu ulogu, ali pod određenim uslovima može da postane hronično stanje koje značajno narušava kvalitet života. Postojeći analgetici, iako nesumnjivo korisni u terapiji različitih bolnih stanja, neretko su nedovoljno efikasni ili bezbedni. Zato postoji potreba za razvojem novih ili otkrivanjem efikasnih kombinacija postojećih analgetika kako bi se poboljšala terapija bola.Ciljevi ovog rada su bili ispitivanje efekata, mehanizama dejstva i interakcija dva potencijalna alternativna analgetika, antiepileptika eslikarbazepin acetata (ESL) i antidijabetika metformina u modelima inflamatornog i neuropatskog bola.Efekti ESL i metformina su ispitani u modelima inflamatornog trigeminalnog, visceralnog i somatskog bola, kao i modelu bolne dijabetesne neuropatije. Mehanizmi dejstva ESL u modelu trigeminalnog bola su ispitani farmakološkim pristupom, korišćenjem antagonista receptora značajnih za modulaciju bola. Vrsta interakcije između ESL/metformina i analgetika u modelima inflamatornog i neuropatskog bola je utvrđena izobolografskom analizom.ESL i metformin su pokazali efikasnost u svim korišćenim modelima inflamatornog bola i u modelu bolne dijabetesne neuropatije. Utvrđeno je da ESL ublažava trigeminalni bol posredstvom serotoninskih 5-HT1B/1D, α2/β1-adrenergičkih, muskarinskih, CB1/CB2 kanabinoidnih i opioidnih receptora. ESL i metformin stupaju u aditivne ili sinergističke interakcije sa različitim analgeticima u modelima inflamatornog i neuropatskog bola.Efikasnost ESL i metformina u modelima bola bi mogla da ukaže na njihovu potencijalnu kliničku primenu kao analgetika. Dodatno, poznavanje mehanizama dejstva ESL može doprineti uspešnoj primeni ovog leka u terapiji bola. Na kraju, oba leka stupaju u povoljne interakcije sa postojećim analgeticima. Ovaj nalaz ukazuje na potencijalno bolju efikasnost i/ili bezbednost kombinovane u odnosu na monoterapiju, kao i koji analgetici bi mogli biti povoljan izbor za lečenje bola kod ljudi koji već primenjuju ESL/metformin zbog komorbiditeta.
AB  - Pain is a complex sensory experience, which has a clear protective role, but under certain circumstances pain can become a chronic condition that significantly impairs the quality of life. Existing analgesics, although undoubtedly useful in the treatment of various painful conditions, are often insufficiently effective or safe. Therefore, there is a need to develop new drugs or to discover effective combinations of existing drugs in order to improve pain therapy.The objectives of this study were to investigate the effects, mechanisms of action, and interactions of two potential alternative analgesics, the antiepileptic eslicarbazepine acetate (ESL) and the antidiabetic metformin in models of inflammatory and neuropathic pain.The effects of ESL and metformin were examined in models of inflammatory trigeminal, visceral and somatic pain, as well as in a model of painful diabetic neuropathy. The mechanisms of action of ESL in the model of trigeminal pain were examined by a pharmacological approach, using antagonists of different receptors important for pain modulation. The type of interaction between ESL/metformin and analgesics in models of inflammatory and neuropathic pain was determined using isobolographic analysis.ESL and metformin were effective in all models of inflammatory pain that were used, as well as in the model of painful diabetic neuropathy. ESL was found to relieve trigeminal pain by activating serotonin 5-HT1B/1D, α2/β1-adrenergic, muscarinic, CB1/CB2 cannabinoid and opioid receptors. ESL and metformin interacted in an additive or synergistic manner with different analgesics in models of inflammatory and neuropathic pain.The efficacy of ESL and metformin in pain models may indicate their potential clinical application as analgesics. In addition, knowledge of the mechanisms of action of ESL may contribute to the successful use of this drug in the treatment of pain. Finally, both drugs interact favorably with existing analgesics. This finding indicates potentially better efficacy and/or safety of combination therapy compared to monotherapy, as well as which analgesics could be a favorable choice for the treatment of pain in people already using ESL/metformin due to comorbidities.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Ispitivanje efekata, mehanizama dejstva i interakcija eslikarbazepin acetata i metformina u eksperimentalnim modelima bola
UR  - https://hdl.handle.net/21.15107/rcub_nardus_18520
ER  - 

@phdthesis{
author = "Pecikoza, Uroš",
year = "2021",
abstract = "Bol je kompleksno senzorno iskustvo koje ima jasnu zaštitnu ulogu, ali pod određenim uslovima može da postane hronično stanje koje značajno narušava kvalitet života. Postojeći analgetici, iako nesumnjivo korisni u terapiji različitih bolnih stanja, neretko su nedovoljno efikasni ili bezbedni. Zato postoji potreba za razvojem novih ili otkrivanjem efikasnih kombinacija postojećih analgetika kako bi se poboljšala terapija bola.Ciljevi ovog rada su bili ispitivanje efekata, mehanizama dejstva i interakcija dva potencijalna alternativna analgetika, antiepileptika eslikarbazepin acetata (ESL) i antidijabetika metformina u modelima inflamatornog i neuropatskog bola.Efekti ESL i metformina su ispitani u modelima inflamatornog trigeminalnog, visceralnog i somatskog bola, kao i modelu bolne dijabetesne neuropatije. Mehanizmi dejstva ESL u modelu trigeminalnog bola su ispitani farmakološkim pristupom, korišćenjem antagonista receptora značajnih za modulaciju bola. Vrsta interakcije između ESL/metformina i analgetika u modelima inflamatornog i neuropatskog bola je utvrđena izobolografskom analizom.ESL i metformin su pokazali efikasnost u svim korišćenim modelima inflamatornog bola i u modelu bolne dijabetesne neuropatije. Utvrđeno je da ESL ublažava trigeminalni bol posredstvom serotoninskih 5-HT1B/1D, α2/β1-adrenergičkih, muskarinskih, CB1/CB2 kanabinoidnih i opioidnih receptora. ESL i metformin stupaju u aditivne ili sinergističke interakcije sa različitim analgeticima u modelima inflamatornog i neuropatskog bola.Efikasnost ESL i metformina u modelima bola bi mogla da ukaže na njihovu potencijalnu kliničku primenu kao analgetika. Dodatno, poznavanje mehanizama dejstva ESL može doprineti uspešnoj primeni ovog leka u terapiji bola. Na kraju, oba leka stupaju u povoljne interakcije sa postojećim analgeticima. Ovaj nalaz ukazuje na potencijalno bolju efikasnost i/ili bezbednost kombinovane u odnosu na monoterapiju, kao i koji analgetici bi mogli biti povoljan izbor za lečenje bola kod ljudi koji već primenjuju ESL/metformin zbog komorbiditeta., Pain is a complex sensory experience, which has a clear protective role, but under certain circumstances pain can become a chronic condition that significantly impairs the quality of life. Existing analgesics, although undoubtedly useful in the treatment of various painful conditions, are often insufficiently effective or safe. Therefore, there is a need to develop new drugs or to discover effective combinations of existing drugs in order to improve pain therapy.The objectives of this study were to investigate the effects, mechanisms of action, and interactions of two potential alternative analgesics, the antiepileptic eslicarbazepine acetate (ESL) and the antidiabetic metformin in models of inflammatory and neuropathic pain.The effects of ESL and metformin were examined in models of inflammatory trigeminal, visceral and somatic pain, as well as in a model of painful diabetic neuropathy. The mechanisms of action of ESL in the model of trigeminal pain were examined by a pharmacological approach, using antagonists of different receptors important for pain modulation. The type of interaction between ESL/metformin and analgesics in models of inflammatory and neuropathic pain was determined using isobolographic analysis.ESL and metformin were effective in all models of inflammatory pain that were used, as well as in the model of painful diabetic neuropathy. ESL was found to relieve trigeminal pain by activating serotonin 5-HT1B/1D, α2/β1-adrenergic, muscarinic, CB1/CB2 cannabinoid and opioid receptors. ESL and metformin interacted in an additive or synergistic manner with different analgesics in models of inflammatory and neuropathic pain.The efficacy of ESL and metformin in pain models may indicate their potential clinical application as analgesics. In addition, knowledge of the mechanisms of action of ESL may contribute to the successful use of this drug in the treatment of pain. Finally, both drugs interact favorably with existing analgesics. This finding indicates potentially better efficacy and/or safety of combination therapy compared to monotherapy, as well as which analgesics could be a favorable choice for the treatment of pain in people already using ESL/metformin due to comorbidities.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Ispitivanje efekata, mehanizama dejstva i interakcija eslikarbazepin acetata i metformina u eksperimentalnim modelima bola",
url = "https://hdl.handle.net/21.15107/rcub_nardus_18520"
}

Pecikoza, U.. (2021). Ispitivanje efekata, mehanizama dejstva i interakcija eslikarbazepin acetata i metformina u eksperimentalnim modelima bola. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_18520

Pecikoza U. Ispitivanje efekata, mehanizama dejstva i interakcija eslikarbazepin acetata i metformina u eksperimentalnim modelima bola. in Универзитет у Београду. 2021;.
https://hdl.handle.net/21.15107/rcub_nardus_18520 .

Pecikoza, Uroš, "Ispitivanje efekata, mehanizama dejstva i interakcija eslikarbazepin acetata i metformina u eksperimentalnim modelima bola" in Универзитет у Београду (2021),
https://hdl.handle.net/21.15107/rcub_nardus_18520 .

TY  - JOUR
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Todorović, Marija B.
AU  - Vuković, Milja
AU  - Pecikoza, Uroš
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena D.
AU  - Stepanović-Petrović, Radica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3600
AB  - Chronic pain and depression commonly occur together so dual-acting agents might be particularly useful. The population of patients with chemotherapy-induced neuropathy is increasing in parallel with the increase of population of cancer survivors and there is a compelling need for satisfactory treatment of symptoms of neuropathy and concomitant depression. We examined the effects of vortioxetine, a novel antidepressant with unique mechanism of action, on pain hypersensitivity and depression-like behavior in oxaliplatin-induced neuropathy model in mice (OIPN). Vortioxetine (1–10 mg/kg, p.o.) significantly and dose-dependently reduced mechanical allodynia in von Frey test and cold allodynia in acetone test in OIPN mice, in both repeated prophylactic and acute therapeutic treatment regimens. It also reduced depression-like behavior in the forced swimming test in OIPN mice, in both treatment paradigms. Its antiallodynic and antidepressive-like effects were comparable to those exerted by duloxetine (1–15 mg/kg, p.o.). The antiallodynic and antidepressive-like effects of repeatedly administered vortioxetine might be related to the increased content of 5-hydroxytryptamine (5- HT) and noradrenaline (NA), detected in the brainstem of treated OIPN mice. These results indicate that vortioxetine could be potentially useful in prevention and treatment of chemotherapy-induced neuropathy, for the relief of pain and concomitant depressive symptoms. It should be further tested to this regard in clinical settings.
PB  - Elsevier
T2  - Progress in Neuro-Psychopharmacology and Biological Psychiatry
T1  - Vortioxetine reduces pain hypersensitivity and associated depression-like behavior in mice with oxaliplatin-induced neuropathy
VL  - 103
DO  - 10.1016/j.pnpbp.2020.109975
ER  - 

@article{
author = "Micov, Ana and Tomić, Maja and Todorović, Marija B. and Vuković, Milja and Pecikoza, Uroš and Jasnić, Nebojša and Đorđević, Jelena D. and Stepanović-Petrović, Radica",
year = "2020",
abstract = "Chronic pain and depression commonly occur together so dual-acting agents might be particularly useful. The population of patients with chemotherapy-induced neuropathy is increasing in parallel with the increase of population of cancer survivors and there is a compelling need for satisfactory treatment of symptoms of neuropathy and concomitant depression. We examined the effects of vortioxetine, a novel antidepressant with unique mechanism of action, on pain hypersensitivity and depression-like behavior in oxaliplatin-induced neuropathy model in mice (OIPN). Vortioxetine (1–10 mg/kg, p.o.) significantly and dose-dependently reduced mechanical allodynia in von Frey test and cold allodynia in acetone test in OIPN mice, in both repeated prophylactic and acute therapeutic treatment regimens. It also reduced depression-like behavior in the forced swimming test in OIPN mice, in both treatment paradigms. Its antiallodynic and antidepressive-like effects were comparable to those exerted by duloxetine (1–15 mg/kg, p.o.). The antiallodynic and antidepressive-like effects of repeatedly administered vortioxetine might be related to the increased content of 5-hydroxytryptamine (5- HT) and noradrenaline (NA), detected in the brainstem of treated OIPN mice. These results indicate that vortioxetine could be potentially useful in prevention and treatment of chemotherapy-induced neuropathy, for the relief of pain and concomitant depressive symptoms. It should be further tested to this regard in clinical settings.",
publisher = "Elsevier",
journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",
title = "Vortioxetine reduces pain hypersensitivity and associated depression-like behavior in mice with oxaliplatin-induced neuropathy",
volume = "103",
doi = "10.1016/j.pnpbp.2020.109975"
}

Micov, A., Tomić, M., Todorović, M. B., Vuković, M., Pecikoza, U., Jasnić, N., Đorđević, J. D.,& Stepanović-Petrović, R.. (2020). Vortioxetine reduces pain hypersensitivity and associated depression-like behavior in mice with oxaliplatin-induced neuropathy. in Progress in Neuro-Psychopharmacology and Biological Psychiatry
Elsevier., 103.
https://doi.org/10.1016/j.pnpbp.2020.109975

Micov A, Tomić M, Todorović MB, Vuković M, Pecikoza U, Jasnić N, Đorđević JD, Stepanović-Petrović R. Vortioxetine reduces pain hypersensitivity and associated depression-like behavior in mice with oxaliplatin-induced neuropathy. in Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2020;103.
doi:10.1016/j.pnpbp.2020.109975 .

Micov, Ana, Tomić, Maja, Todorović, Marija B., Vuković, Milja, Pecikoza, Uroš, Jasnić, Nebojša, Đorđević, Jelena D., Stepanović-Petrović, Radica, "Vortioxetine reduces pain hypersensitivity and associated depression-like behavior in mice with oxaliplatin-induced neuropathy" in Progress in Neuro-Psychopharmacology and Biological Psychiatry, 103 (2020),
https://doi.org/10.1016/j.pnpbp.2020.109975 . .

TY  - JOUR
AU  - Đekić, Ljiljana
AU  - Marković, Bojan
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Stepanović-Petrović, Radica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3589
AB  - The study focused on formulation of carmellose sodium hydrogels and nonionic microemulsions with 5% and 10% of levetiracetam and investigation of drug concentration influence on their physicochemical characteristics and in-use stability as well as influence of drug concentration and carrier type on in vitro drug release and in vivo antihyperalgesic/antiedematous activity in a rat model of localized (intraplantar) carrageenan-induced inflammation. Hydrogels were pseudoplastic semisolids with thixotropy and pH 7.37–7.58. Microemulsions were low viscous Newtonian nanodispersions of oil droplets (13.11–15.11 nm) in water, with pH 4.01–4.64. Physical stability of the investigated systems was preserved over the 3-month storage under ambient conditions. Levetiracetam release followed zero order and Korsmeyer-Peppas models (R2 ≥ 0.99) reflecting the combined effects of drug concentration and carrier viscosity. All levetiracetam-loaded formulations produced significant reduction of hyperalgesia and paw swelling induced by carrageenan (p < 0.001). Their efficacy in exerting antihyperalgesic activity was significantly higher than that observed with the reference 5% ibuprofen hydrogel preparation (up to 6 h) (p < 0.001), while antiedematous activity was comparable with the reference product. No erythema and visible blood vessels were observed in a rat ear test. The study demonstrated percutaneous delivery of levetiracetam as useful and safe therapeutic option for localized inflammatory pain with potential to overcome the insufficient efficacy of topically applied nonsteroidal anti-inflammatory drugs in the form of a hydrogel. [Figure not available: see fulltext.]. © 2020, Controlled Release Society.
PB  - Springer
T2  - Drug Delivery and Translational Research
T1  - Percutaneous delivery of levetiracetam as an alternative to topical nonsteroidal anti-inflammatory drugs: formulation development, in vitro and in vivo characterization
DO  - 10.1007/s13346-020-00787-4
ER  - 

@article{
author = "Đekić, Ljiljana and Marković, Bojan and Micov, Ana and Tomić, Maja and Pecikoza, Uroš and Stepanović-Petrović, Radica",
year = "2020",
abstract = "The study focused on formulation of carmellose sodium hydrogels and nonionic microemulsions with 5% and 10% of levetiracetam and investigation of drug concentration influence on their physicochemical characteristics and in-use stability as well as influence of drug concentration and carrier type on in vitro drug release and in vivo antihyperalgesic/antiedematous activity in a rat model of localized (intraplantar) carrageenan-induced inflammation. Hydrogels were pseudoplastic semisolids with thixotropy and pH 7.37–7.58. Microemulsions were low viscous Newtonian nanodispersions of oil droplets (13.11–15.11 nm) in water, with pH 4.01–4.64. Physical stability of the investigated systems was preserved over the 3-month storage under ambient conditions. Levetiracetam release followed zero order and Korsmeyer-Peppas models (R2 ≥ 0.99) reflecting the combined effects of drug concentration and carrier viscosity. All levetiracetam-loaded formulations produced significant reduction of hyperalgesia and paw swelling induced by carrageenan (p < 0.001). Their efficacy in exerting antihyperalgesic activity was significantly higher than that observed with the reference 5% ibuprofen hydrogel preparation (up to 6 h) (p < 0.001), while antiedematous activity was comparable with the reference product. No erythema and visible blood vessels were observed in a rat ear test. The study demonstrated percutaneous delivery of levetiracetam as useful and safe therapeutic option for localized inflammatory pain with potential to overcome the insufficient efficacy of topically applied nonsteroidal anti-inflammatory drugs in the form of a hydrogel. [Figure not available: see fulltext.]. © 2020, Controlled Release Society.",
publisher = "Springer",
journal = "Drug Delivery and Translational Research",
title = "Percutaneous delivery of levetiracetam as an alternative to topical nonsteroidal anti-inflammatory drugs: formulation development, in vitro and in vivo characterization",
doi = "10.1007/s13346-020-00787-4"
}

Đekić, L., Marković, B., Micov, A., Tomić, M., Pecikoza, U.,& Stepanović-Petrović, R.. (2020). Percutaneous delivery of levetiracetam as an alternative to topical nonsteroidal anti-inflammatory drugs: formulation development, in vitro and in vivo characterization. in Drug Delivery and Translational Research
Springer..
https://doi.org/10.1007/s13346-020-00787-4

Đekić L, Marković B, Micov A, Tomić M, Pecikoza U, Stepanović-Petrović R. Percutaneous delivery of levetiracetam as an alternative to topical nonsteroidal anti-inflammatory drugs: formulation development, in vitro and in vivo characterization. in Drug Delivery and Translational Research. 2020;.
doi:10.1007/s13346-020-00787-4 .

Đekić, Ljiljana, Marković, Bojan, Micov, Ana, Tomić, Maja, Pecikoza, Uroš, Stepanović-Petrović, Radica, "Percutaneous delivery of levetiracetam as an alternative to topical nonsteroidal anti-inflammatory drugs: formulation development, in vitro and in vivo characterization" in Drug Delivery and Translational Research (2020),
https://doi.org/10.1007/s13346-020-00787-4 . .

TY  - JOUR
AU  - Pecikoza, Uroš
AU  - Tomić, Maja
AU  - Micov, Ana
AU  - Vuković, Milja
AU  - Stepanović-Petrović, Radica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3547
AB  - Rationale: Acute pain states in the trigeminal region (headaches, dental pain) fall into the most prevalent painful conditions. Standard analgesics (paracetamol/NSAIDs) represent the cornerstone of their treatment, whereas triptans are primarily used in migraine attacks. Due to limited efficacy and/or side effects of current treatments, identifying favorable combinations of available drugs is justified. Objectives: Eslicarbazepine acetate (ESL) is a novel antiepileptic drug whose effectiveness against trigeminal pain was recently demonstrated. Here, we examined the interactions between ESL and several standard/alternative analgesics (paracetamol, propyphenazone, naproxen, zolmitriptan, and metoclopramide) in a model of trigeminal pain. Methods: The antinociceptive effects of orally administered ESL, standard/alternative analgesics, and two-drug ESL-analgesic combinations were examined in the orofacial formalin test in mice. The type of interaction between drugs was determined by isobolographic analysis. Results: ESL, analgesics, and two-drug ESL-analgesic combinations significantly and dose-dependently reduced nociceptive behaviour in the second, inflammatory phase of the test. Isobolographic analysis revealed that ESL interacted additively with paracetamol/propyphenazone/zolmitriptan and synergistically with naproxen/metoclopramide (with about a 4-fold and 3-fold reduction of doses in the ESL-naproxen and ESL-metoclopramide combination, respectively). Conclusions: ESL interacted in a beneficial manner with several analgesics that are used for trigeminal pain treatment, producing synergistic interactions with naproxen/metoclopramide and additive interactions with paracetamol/propyphenazone/zolmitriptan. Our results suggest that combining ESL with analgesics could theoretically enable the use of lower doses of individual drugs for achieving pain relief.
PB  - Springer Nature
T2  - Psychopharmacology
T1  - Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception
VL  - 237
IS  - 5
SP  - 1435
EP  - 1446
DO  - 10.1007/s00213-020-05470-7
ER  - 

@article{
author = "Pecikoza, Uroš and Tomić, Maja and Micov, Ana and Vuković, Milja and Stepanović-Petrović, Radica",
year = "2020",
abstract = "Rationale: Acute pain states in the trigeminal region (headaches, dental pain) fall into the most prevalent painful conditions. Standard analgesics (paracetamol/NSAIDs) represent the cornerstone of their treatment, whereas triptans are primarily used in migraine attacks. Due to limited efficacy and/or side effects of current treatments, identifying favorable combinations of available drugs is justified. Objectives: Eslicarbazepine acetate (ESL) is a novel antiepileptic drug whose effectiveness against trigeminal pain was recently demonstrated. Here, we examined the interactions between ESL and several standard/alternative analgesics (paracetamol, propyphenazone, naproxen, zolmitriptan, and metoclopramide) in a model of trigeminal pain. Methods: The antinociceptive effects of orally administered ESL, standard/alternative analgesics, and two-drug ESL-analgesic combinations were examined in the orofacial formalin test in mice. The type of interaction between drugs was determined by isobolographic analysis. Results: ESL, analgesics, and two-drug ESL-analgesic combinations significantly and dose-dependently reduced nociceptive behaviour in the second, inflammatory phase of the test. Isobolographic analysis revealed that ESL interacted additively with paracetamol/propyphenazone/zolmitriptan and synergistically with naproxen/metoclopramide (with about a 4-fold and 3-fold reduction of doses in the ESL-naproxen and ESL-metoclopramide combination, respectively). Conclusions: ESL interacted in a beneficial manner with several analgesics that are used for trigeminal pain treatment, producing synergistic interactions with naproxen/metoclopramide and additive interactions with paracetamol/propyphenazone/zolmitriptan. Our results suggest that combining ESL with analgesics could theoretically enable the use of lower doses of individual drugs for achieving pain relief.",
publisher = "Springer Nature",
journal = "Psychopharmacology",
title = "Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception",
volume = "237",
number = "5",
pages = "1435-1446",
doi = "10.1007/s00213-020-05470-7"
}

Pecikoza, U., Tomić, M., Micov, A., Vuković, M.,& Stepanović-Petrović, R.. (2020). Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception. in Psychopharmacology
Springer Nature., 237(5), 1435-1446.
https://doi.org/10.1007/s00213-020-05470-7

Pecikoza U, Tomić M, Micov A, Vuković M, Stepanović-Petrović R. Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception. in Psychopharmacology. 2020;237(5):1435-1446.
doi:10.1007/s00213-020-05470-7 .

Pecikoza, Uroš, Tomić, Maja, Micov, Ana, Vuković, Milja, Stepanović-Petrović, Radica, "Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception" in Psychopharmacology, 237, no. 5 (2020):1435-1446,
https://doi.org/10.1007/s00213-020-05470-7 . .

TY  - JOUR
AU  - Pecikoza, Uroš
AU  - Tomić, Maja
AU  - Micov, Ana
AU  - Vuković, Milja
AU  - Stepanović-Petrović, Radica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3546
AB  - Rationale: Acute pain states in the trigeminal region (headaches, dental pain) fall into the most prevalent painful conditions. Standard analgesics (paracetamol/NSAIDs) represent the cornerstone of their treatment, whereas triptans are primarily used in migraine attacks. Due to limited efficacy and/or side effects of current treatments, identifying favorable combinations of available drugs is justified.
Objectives: Eslicarbazepine acetate (ESL) is a novel antiepileptic drug whose effectiveness against trigeminal pain was recently demonstrated. Here, we examined the interactions between ESL and several standard/alternative analgesics (paracetamol, propyphenazone, naproxen, zolmitriptan, and metoclopramide) in a model of trigeminal pain.
Methods: The antinociceptive effects of orally administered ESL, standard/alternative analgesics, and two-drug ESL-analgesic combinations were examined in the orofacial formalin test in mice. The type of interaction between drugs was determined by isobolographic analysis.
Results: ESL, analgesics, and two-drug ESL-analgesic combinations significantly and dose-dependently reduced nociceptive behaviour in the second, inflammatory phase of the test. Isobolographic analysis revealed that ESL interacted additively with paracetamol/propyphenazone/zolmitriptan and synergistically with naproxen/metoclopramide (with about a 4-fold and 3-fold reduction of doses in the ESL-naproxen and ESL-metoclopramide combination, respectively).
Conclusions: ESL interacted in a beneficial manner with several analgesics that are used for trigeminal pain treatment, producing synergistic interactions with naproxen/metoclopramide and additive interactions with paracetamol/propyphenazone/zolmitriptan. Our results suggest that combining ESL with analgesics could theoretically enable the use of lower doses of individual drugs for achieving pain relief.
PB  - Springer-Verlag
T2  - Psychopharmacology
T1  - Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception
DO  - 10.1007/s00213-020-05470-7
ER  - 

@article{
author = "Pecikoza, Uroš and Tomić, Maja and Micov, Ana and Vuković, Milja and Stepanović-Petrović, Radica",
year = "2020",
abstract = "Rationale: Acute pain states in the trigeminal region (headaches, dental pain) fall into the most prevalent painful conditions. Standard analgesics (paracetamol/NSAIDs) represent the cornerstone of their treatment, whereas triptans are primarily used in migraine attacks. Due to limited efficacy and/or side effects of current treatments, identifying favorable combinations of available drugs is justified.
Objectives: Eslicarbazepine acetate (ESL) is a novel antiepileptic drug whose effectiveness against trigeminal pain was recently demonstrated. Here, we examined the interactions between ESL and several standard/alternative analgesics (paracetamol, propyphenazone, naproxen, zolmitriptan, and metoclopramide) in a model of trigeminal pain.
Methods: The antinociceptive effects of orally administered ESL, standard/alternative analgesics, and two-drug ESL-analgesic combinations were examined in the orofacial formalin test in mice. The type of interaction between drugs was determined by isobolographic analysis.
Results: ESL, analgesics, and two-drug ESL-analgesic combinations significantly and dose-dependently reduced nociceptive behaviour in the second, inflammatory phase of the test. Isobolographic analysis revealed that ESL interacted additively with paracetamol/propyphenazone/zolmitriptan and synergistically with naproxen/metoclopramide (with about a 4-fold and 3-fold reduction of doses in the ESL-naproxen and ESL-metoclopramide combination, respectively).
Conclusions: ESL interacted in a beneficial manner with several analgesics that are used for trigeminal pain treatment, producing synergistic interactions with naproxen/metoclopramide and additive interactions with paracetamol/propyphenazone/zolmitriptan. Our results suggest that combining ESL with analgesics could theoretically enable the use of lower doses of individual drugs for achieving pain relief.",
publisher = "Springer-Verlag",
journal = "Psychopharmacology",
title = "Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception",
doi = "10.1007/s00213-020-05470-7"
}

Pecikoza, U., Tomić, M., Micov, A., Vuković, M.,& Stepanović-Petrović, R.. (2020). Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception. in Psychopharmacology
Springer-Verlag..
https://doi.org/10.1007/s00213-020-05470-7

Pecikoza U, Tomić M, Micov A, Vuković M, Stepanović-Petrović R. Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception. in Psychopharmacology. 2020;.
doi:10.1007/s00213-020-05470-7 .

Pecikoza, Uroš, Tomić, Maja, Micov, Ana, Vuković, Milja, Stepanović-Petrović, Radica, "Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception" in Psychopharmacology (2020),
https://doi.org/10.1007/s00213-020-05470-7 . .

TY  - CONF
AU  - Milutinović, Violeta
AU  - Pecikoza, Uroš
AU  - Tomić, Maja
AU  - Stepanović-Petrović, Radica
AU  - Niketić, Marjan
AU  - Ušjak, Ljuboš
AU  - Petrović, Silvana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5281
AB  - Rod Hieracium s. str. (Asteraceae) je autohton na teritoriji Evroazije, severne Afrike i Severne Amerike, sa velikim brojem taksona rasprostranjenih u Evropi. ...
AB  - Genus Hieracium s. str. (Asteraceae) is autochthonous in Eurasia, North Africa and North America, with the vast majority of taxa being distributed in Europe. ...
PB  - Srpsko farmakološko društvo (SFD)
C3  - 14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem. Novi Sad, 18-21.09.2019. Zbornik kratkih sadržaja radova
T1  - Ispitivanje antihiperalgezijske i antiedematozne aktivnosti ekstrakata nadzemnih delova u cvetu tri vrste roda Hieracium
T1  - Investigation of antihyperalgesic and antiedematous activities of the flowering aerial parts extracts of three Hieracium species
SP  - 176
EP  - 177
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5281
ER  - 

@conference{
author = "Milutinović, Violeta and Pecikoza, Uroš and Tomić, Maja and Stepanović-Petrović, Radica and Niketić, Marjan and Ušjak, Ljuboš and Petrović, Silvana",
year = "2019",
abstract = "Rod Hieracium s. str. (Asteraceae) je autohton na teritoriji Evroazije, severne Afrike i Severne Amerike, sa velikim brojem taksona rasprostranjenih u Evropi. ..., Genus Hieracium s. str. (Asteraceae) is autochthonous in Eurasia, North Africa and North America, with the vast majority of taxa being distributed in Europe. ...",
publisher = "Srpsko farmakološko društvo (SFD)",
journal = "14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem. Novi Sad, 18-21.09.2019. Zbornik kratkih sadržaja radova",
title = "Ispitivanje antihiperalgezijske i antiedematozne aktivnosti ekstrakata nadzemnih delova u cvetu tri vrste roda Hieracium, Investigation of antihyperalgesic and antiedematous activities of the flowering aerial parts extracts of three Hieracium species",
pages = "176-177",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5281"
}

Milutinović, V., Pecikoza, U., Tomić, M., Stepanović-Petrović, R., Niketić, M., Ušjak, L.,& Petrović, S.. (2019). Ispitivanje antihiperalgezijske i antiedematozne aktivnosti ekstrakata nadzemnih delova u cvetu tri vrste roda Hieracium. in 14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem. Novi Sad, 18-21.09.2019. Zbornik kratkih sadržaja radova
Srpsko farmakološko društvo (SFD)., 176-177.
https://hdl.handle.net/21.15107/rcub_farfar_5281

Milutinović V, Pecikoza U, Tomić M, Stepanović-Petrović R, Niketić M, Ušjak L, Petrović S. Ispitivanje antihiperalgezijske i antiedematozne aktivnosti ekstrakata nadzemnih delova u cvetu tri vrste roda Hieracium. in 14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem. Novi Sad, 18-21.09.2019. Zbornik kratkih sadržaja radova. 2019;:176-177.
https://hdl.handle.net/21.15107/rcub_farfar_5281 .

Milutinović, Violeta, Pecikoza, Uroš, Tomić, Maja, Stepanović-Petrović, Radica, Niketić, Marjan, Ušjak, Ljuboš, Petrović, Silvana, "Ispitivanje antihiperalgezijske i antiedematozne aktivnosti ekstrakata nadzemnih delova u cvetu tri vrste roda Hieracium" in 14. Kongres farmakologa Srbije i 4. Kongres kliničke farmakologije Srbije sa međunarodnim učešćem. Novi Sad, 18-21.09.2019. Zbornik kratkih sadržaja radova (2019):176-177,
https://hdl.handle.net/21.15107/rcub_farfar_5281 .

TY  - JOUR
AU  - Stepanović-Petrović, Radica
AU  - Tomić, Maja
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3284
AB  - Morphine, as a paradigm of opioids, is 'gold standard' in treating severe pain, to which all other drugs are compared. However, abuse and respiratory depression potentials have resulted in 'opiophobia' among health professionals, and underutilization of opioids as analgesics. But, addiction and respiratory depression are almost never present in pain managenent in palliative care. So, fear of addiction and respiratory depression should not prevent increasing of opioid dose in those patients in paliative care who still suffer of severe pain. Opioids are ineffective in treating neuropathic pain. Antiepileptics (carbamazepine, pregabalin, gabapentin) and antidepressants (amitriptyline, duloxetine) are used for neuropathic pain.
AB  - Morfin, kao primer opioida se smatra 'zlatnim standardom' u lečenju jakih bolova, sa kojim se svi drugi lekovi porede. Međutim, potencijal opioida da izazovu zavisnost/adikciju i depresiju disanja stvorilo je tzv. 'opiofobe' među zdravstvenim radnicima, zbog kojih se opioidi nedovoljno koriste u lečenju jakih bolova. Ali, adikcija i izrazita depresija disanja gotovo nikada ne mogu da se jave u terminalnih pacijenata. Zato strah od zavisnosti i respiratorne depresije ne treba da spreči povećanje doze opioida kada pacijent i dalje pati od bola. Opioidi su slabo efikasni u lečenju neuropatskih bolova. Za lečenje neuropatskih bolova koriste se antiepileptici (karbamazepin, pregabalin, gabapentin) i antidepresivi (amitriptilin, duloksetin).
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Opioids and adjuvant analgesics in current treating of pain
T1  - Opioidni i adjuvantni analgetici u savremenom lečenju bola
VL  - 69
IS  - 1
SP  - 1009
EP  - 1020
DO  - 10.5937/ArhFarm1901009S
ER  - 

@article{
author = "Stepanović-Petrović, Radica and Tomić, Maja",
year = "2019",
abstract = "Morphine, as a paradigm of opioids, is 'gold standard' in treating severe pain, to which all other drugs are compared. However, abuse and respiratory depression potentials have resulted in 'opiophobia' among health professionals, and underutilization of opioids as analgesics. But, addiction and respiratory depression are almost never present in pain managenent in palliative care. So, fear of addiction and respiratory depression should not prevent increasing of opioid dose in those patients in paliative care who still suffer of severe pain. Opioids are ineffective in treating neuropathic pain. Antiepileptics (carbamazepine, pregabalin, gabapentin) and antidepressants (amitriptyline, duloxetine) are used for neuropathic pain., Morfin, kao primer opioida se smatra 'zlatnim standardom' u lečenju jakih bolova, sa kojim se svi drugi lekovi porede. Međutim, potencijal opioida da izazovu zavisnost/adikciju i depresiju disanja stvorilo je tzv. 'opiofobe' među zdravstvenim radnicima, zbog kojih se opioidi nedovoljno koriste u lečenju jakih bolova. Ali, adikcija i izrazita depresija disanja gotovo nikada ne mogu da se jave u terminalnih pacijenata. Zato strah od zavisnosti i respiratorne depresije ne treba da spreči povećanje doze opioida kada pacijent i dalje pati od bola. Opioidi su slabo efikasni u lečenju neuropatskih bolova. Za lečenje neuropatskih bolova koriste se antiepileptici (karbamazepin, pregabalin, gabapentin) i antidepresivi (amitriptilin, duloksetin).",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Opioids and adjuvant analgesics in current treating of pain, Opioidni i adjuvantni analgetici u savremenom lečenju bola",
volume = "69",
number = "1",
pages = "1009-1020",
doi = "10.5937/ArhFarm1901009S"
}

Stepanović-Petrović, R.,& Tomić, M.. (2019). Opioids and adjuvant analgesics in current treating of pain. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 69(1), 1009-1020.
https://doi.org/10.5937/ArhFarm1901009S

Stepanović-Petrović R, Tomić M. Opioids and adjuvant analgesics in current treating of pain. in Arhiv za farmaciju. 2019;69(1):1009-1020.
doi:10.5937/ArhFarm1901009S .

Stepanović-Petrović, Radica, Tomić, Maja, "Opioids and adjuvant analgesics in current treating of pain" in Arhiv za farmaciju, 69, no. 1 (2019):1009-1020,
https://doi.org/10.5937/ArhFarm1901009S . .

TY  - JOUR
AU  - Đekić, Ljiljana
AU  - Čalija, Bojan
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Stepanović-Petrović, Radica
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3268
AB  - The physicochemical properties, stability, in vivo antihyperalgesic activity, and skin irritation potential of the carbomer hydrogels with the new chemical entity escin β-sitosterol (ES) phytosome were characterized and compared with those containing escin. Physicochemical characterization of the hydrogels (performed 48 hr after preparation) included organoleptic examination, pH measurement, light microscopy, differential scanning calorimetry analysis and rheological tests. The obtained results showed that increasing concentration of the active substances within 1–5% affected the appearance (color and transparency) of the hydrogels, their pH, consistency, and rheological behavior. Unlike acidic escin, which was dissolved in the liquid phase of the pseudoplastic hydrogels E1–E5 and reduced their maximal apparent viscosity (ηmax), minimal apparent viscosity (ηmin), and hysteresis area (H) in comparison to the plain carbomer hydrogel, amphiphilic ES-enhanced ηmax, ηmin, and thixotropy of the hydrogels ES1–ES5, which is favorable for prolonged retention at skin surface. Evaluation of in-use stability of the hydrogels showed that organoleptic characteristics, flow behavior, and pH values could be preserved for 3 months under ambient conditions. The rat ear test results suggested that the hydrogels are safe to be used on human skin. Both escin and ES-loaded hydrogels exerted significant, concentration-dependent antihyperalgesic effect in inflammatory pain model in rats. ES-loaded hydrogels were significantly more effective than those loaded with escin. This is a first report on the antihyperalgesic effect of topically applied escin as well as ES in a model of inflammatory pain.
PB  - Wiley-Liss Inc.
T2  - Drug Development Research
T1  - Topical hydrogels with escin β-sitosterol phytosome and escin: Formulation development and in vivo assessment of antihyperalgesic activity
DO  - 10.1002/ddr.21572
ER  - 

@article{
author = "Đekić, Ljiljana and Čalija, Bojan and Micov, Ana and Tomić, Maja and Stepanović-Petrović, Radica",
year = "2019",
abstract = "The physicochemical properties, stability, in vivo antihyperalgesic activity, and skin irritation potential of the carbomer hydrogels with the new chemical entity escin β-sitosterol (ES) phytosome were characterized and compared with those containing escin. Physicochemical characterization of the hydrogels (performed 48 hr after preparation) included organoleptic examination, pH measurement, light microscopy, differential scanning calorimetry analysis and rheological tests. The obtained results showed that increasing concentration of the active substances within 1–5% affected the appearance (color and transparency) of the hydrogels, their pH, consistency, and rheological behavior. Unlike acidic escin, which was dissolved in the liquid phase of the pseudoplastic hydrogels E1–E5 and reduced their maximal apparent viscosity (ηmax), minimal apparent viscosity (ηmin), and hysteresis area (H) in comparison to the plain carbomer hydrogel, amphiphilic ES-enhanced ηmax, ηmin, and thixotropy of the hydrogels ES1–ES5, which is favorable for prolonged retention at skin surface. Evaluation of in-use stability of the hydrogels showed that organoleptic characteristics, flow behavior, and pH values could be preserved for 3 months under ambient conditions. The rat ear test results suggested that the hydrogels are safe to be used on human skin. Both escin and ES-loaded hydrogels exerted significant, concentration-dependent antihyperalgesic effect in inflammatory pain model in rats. ES-loaded hydrogels were significantly more effective than those loaded with escin. This is a first report on the antihyperalgesic effect of topically applied escin as well as ES in a model of inflammatory pain.",
publisher = "Wiley-Liss Inc.",
journal = "Drug Development Research",
title = "Topical hydrogels with escin β-sitosterol phytosome and escin: Formulation development and in vivo assessment of antihyperalgesic activity",
doi = "10.1002/ddr.21572"
}

Đekić, L., Čalija, B., Micov, A., Tomić, M.,& Stepanović-Petrović, R.. (2019). Topical hydrogels with escin β-sitosterol phytosome and escin: Formulation development and in vivo assessment of antihyperalgesic activity. in Drug Development Research
Wiley-Liss Inc...
https://doi.org/10.1002/ddr.21572

Đekić L, Čalija B, Micov A, Tomić M, Stepanović-Petrović R. Topical hydrogels with escin β-sitosterol phytosome and escin: Formulation development and in vivo assessment of antihyperalgesic activity. in Drug Development Research. 2019;.
doi:10.1002/ddr.21572 .

Đekić, Ljiljana, Čalija, Bojan, Micov, Ana, Tomić, Maja, Stepanović-Petrović, Radica, "Topical hydrogels with escin β-sitosterol phytosome and escin: Formulation development and in vivo assessment of antihyperalgesic activity" in Drug Development Research (2019),
https://doi.org/10.1002/ddr.21572 . .

TY  - THES
AU  - Samardžić, Stevan
PY  - 2018
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=6604
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:19401/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=2048320610
UR  - http://nardus.mpn.gov.rs/123456789/10779
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3408
AB  - Filipendula ulmaria i F. vulgaris se tradicionalno koriste kod peptičkog ulkusa i bolnih stanja.Cilj: Liofilizovani infuzi cvasti (LIC) ovih vrsta i izolovana jedinjenja F. vulgaris su podvrgnuti hemijskim i farmakološkim ispitivanjima u cilju preliminarne procene terapijskog potencijala i opravdanosti zabeležene etnomedicinske primene.Metode: Sastav LIC je utvrđen HPLC-UV metodom. Antioksidantna i citotoksična aktivnost je procenjena in vitro, antiinflamatorno dejstvo i antiagregacioni potencijal ex vivo u humanim trombocitima, dok su antihiperalgezijska, antiedematozna, gastroprotektivna aktivnost i akutna toksičnost ispitani in vivo.Rezultati i diskusija: LIC su se karakterisali visokim sadržajem polifenola, izraženom antioksidantnom aktivnošću, slabom sposobnošću inhibicije biosinteze eikozanoida i citotoksičnošću. Antihiperalgezijsko dejstvo LIC (100–300 mg/kg) je bilo statistički značajno i dozno-zavisno: ED50 ± SEM vrednosti u trenutku maksimalnog efekta su iznosile 164,8 ± 15,4 mg/kg (F. ulmaria) i 172,2 ± 6,2 mg/kg (F. vulgaris). LIC (100–300 mg/kg), telimagrandin II (40 mg/kg) i spireozid (50 mg/kg) su redukovali intenzitet gastričnih lezija indukovanih etanolom. Nakon akutne primene velikih doza LIC, nisu uočeni znaci toksičnosti u životinja. U sprovedenim eksperimentima je pokazano da flavonoidi, galna kiselina i telimagrandin II doprinose farmakološkim efektima LIC.Zaključak: Dobijeni rezultati podržavaju primenu cvasti F. ulmaria i F. vulgaris u tradicionalnoj medicini. Polifenoli su aktivni sastojci, što ih čini potencijalnim markerima kvaliteta. Značajna sličnost hemijskih i farmakoloških profila ispitivanih LIC ukazuje da bi vrste F. ulmaria i F. vulgaris mogle da budu ravnopravni biološki izvor biljne droge Filipendulae flos.
AB  - Filipendula ulmaria and F. vulgaris are traditionally used in the treatment of peptic ulcer and pain.Aim of the study: Lyophilized flower infusions (LFIs) of these species and isolated compounds of F. vulgaris were subjected to chemical and pharmacological investigations with the goal to preliminary assess therapeutic potential and validity of the recorded ethnomedicinal use.Methods: Chemical composition of LFIs was analyzed by HPLC-UV method. Antioxidant and cytotoxic activities were assessed in vitro, anti-inflammatory effect and anti-aggregation potential were studied ex vivo in human platelets, whereas antihyperalgesic, antiedematous, gastroprotective activities and acute toxicity were investigated in vivo.Results and discussion: LFIs were characterized by high polyphenolic content, pronounced antioxidant activity, low capacity to inhibit biosynthesis of eicosanoids and cytotoxicity. Antihyperalgesic effect of LFIs (100–300 mg/kg) was statistically significant and dose-dependent: ED50 ± SEM values, obtained at the time of peak effects, were 164.8 ± 15.4 mg/kg (F. ulmaria) and 172.2 ± 6.2 mg/kg (F. vulgaris). LFIs (100–300 mg/kg), tellimagrandin II (40 mg/kg) and spiraeoside (50 mg/kg) reduced intensity of gastric lesions induced by ethanol. After acute application of high LFIs doses, signs of toxicity in animals were not observed. In performed experiments, it was shown that flavonoids, gallic acid and tellimagrandin II contributed to the pharmacological actions of LFIs.Conclusion: The obtained data support use of F. ulmaria and F. vulgaris flowers in traditional medicine. Polyphenols are active constituents, and hence potential quality markers. Significant similarity of chemical and pharmacological profiles of tested LFIs suggests that F. ulmaria and F. vulgaris could be equivalent biological sources of herbal drug Filipendulae flos.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Uporedno hemijsko i farmakološko ispitivanje liofilizovanih infuza cvasti predstavnika roda Filipendula Miller u Srbiji
UR  - https://hdl.handle.net/21.15107/rcub_nardus_10779
ER  - 

@phdthesis{
author = "Samardžić, Stevan",
year = "2018",
abstract = "Filipendula ulmaria i F. vulgaris se tradicionalno koriste kod peptičkog ulkusa i bolnih stanja.Cilj: Liofilizovani infuzi cvasti (LIC) ovih vrsta i izolovana jedinjenja F. vulgaris su podvrgnuti hemijskim i farmakološkim ispitivanjima u cilju preliminarne procene terapijskog potencijala i opravdanosti zabeležene etnomedicinske primene.Metode: Sastav LIC je utvrđen HPLC-UV metodom. Antioksidantna i citotoksična aktivnost je procenjena in vitro, antiinflamatorno dejstvo i antiagregacioni potencijal ex vivo u humanim trombocitima, dok su antihiperalgezijska, antiedematozna, gastroprotektivna aktivnost i akutna toksičnost ispitani in vivo.Rezultati i diskusija: LIC su se karakterisali visokim sadržajem polifenola, izraženom antioksidantnom aktivnošću, slabom sposobnošću inhibicije biosinteze eikozanoida i citotoksičnošću. Antihiperalgezijsko dejstvo LIC (100–300 mg/kg) je bilo statistički značajno i dozno-zavisno: ED50 ± SEM vrednosti u trenutku maksimalnog efekta su iznosile 164,8 ± 15,4 mg/kg (F. ulmaria) i 172,2 ± 6,2 mg/kg (F. vulgaris). LIC (100–300 mg/kg), telimagrandin II (40 mg/kg) i spireozid (50 mg/kg) su redukovali intenzitet gastričnih lezija indukovanih etanolom. Nakon akutne primene velikih doza LIC, nisu uočeni znaci toksičnosti u životinja. U sprovedenim eksperimentima je pokazano da flavonoidi, galna kiselina i telimagrandin II doprinose farmakološkim efektima LIC.Zaključak: Dobijeni rezultati podržavaju primenu cvasti F. ulmaria i F. vulgaris u tradicionalnoj medicini. Polifenoli su aktivni sastojci, što ih čini potencijalnim markerima kvaliteta. Značajna sličnost hemijskih i farmakoloških profila ispitivanih LIC ukazuje da bi vrste F. ulmaria i F. vulgaris mogle da budu ravnopravni biološki izvor biljne droge Filipendulae flos., Filipendula ulmaria and F. vulgaris are traditionally used in the treatment of peptic ulcer and pain.Aim of the study: Lyophilized flower infusions (LFIs) of these species and isolated compounds of F. vulgaris were subjected to chemical and pharmacological investigations with the goal to preliminary assess therapeutic potential and validity of the recorded ethnomedicinal use.Methods: Chemical composition of LFIs was analyzed by HPLC-UV method. Antioxidant and cytotoxic activities were assessed in vitro, anti-inflammatory effect and anti-aggregation potential were studied ex vivo in human platelets, whereas antihyperalgesic, antiedematous, gastroprotective activities and acute toxicity were investigated in vivo.Results and discussion: LFIs were characterized by high polyphenolic content, pronounced antioxidant activity, low capacity to inhibit biosynthesis of eicosanoids and cytotoxicity. Antihyperalgesic effect of LFIs (100–300 mg/kg) was statistically significant and dose-dependent: ED50 ± SEM values, obtained at the time of peak effects, were 164.8 ± 15.4 mg/kg (F. ulmaria) and 172.2 ± 6.2 mg/kg (F. vulgaris). LFIs (100–300 mg/kg), tellimagrandin II (40 mg/kg) and spiraeoside (50 mg/kg) reduced intensity of gastric lesions induced by ethanol. After acute application of high LFIs doses, signs of toxicity in animals were not observed. In performed experiments, it was shown that flavonoids, gallic acid and tellimagrandin II contributed to the pharmacological actions of LFIs.Conclusion: The obtained data support use of F. ulmaria and F. vulgaris flowers in traditional medicine. Polyphenols are active constituents, and hence potential quality markers. Significant similarity of chemical and pharmacological profiles of tested LFIs suggests that F. ulmaria and F. vulgaris could be equivalent biological sources of herbal drug Filipendulae flos.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Uporedno hemijsko i farmakološko ispitivanje liofilizovanih infuza cvasti predstavnika roda Filipendula Miller u Srbiji",
url = "https://hdl.handle.net/21.15107/rcub_nardus_10779"
}

Samardžić, S.. (2018). Uporedno hemijsko i farmakološko ispitivanje liofilizovanih infuza cvasti predstavnika roda Filipendula Miller u Srbiji. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_10779

Samardžić S. Uporedno hemijsko i farmakološko ispitivanje liofilizovanih infuza cvasti predstavnika roda Filipendula Miller u Srbiji. in Универзитет у Београду. 2018;.
https://hdl.handle.net/21.15107/rcub_nardus_10779 .

Samardžić, Stevan, "Uporedno hemijsko i farmakološko ispitivanje liofilizovanih infuza cvasti predstavnika roda Filipendula Miller u Srbiji" in Универзитет у Београду (2018),
https://hdl.handle.net/21.15107/rcub_nardus_10779 .

TY  - THES
AU  - Dinić, Miroslav
PY  - 2018
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=6030
UR  - http://nardus.mpn.gov.rs/handle/123456789/9986
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:18343/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=2048264546
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3680
AB  - Izolacija i karakterizacija bakterijskih biomolekula koji interaguju sa receptorimaćelija domaćina predstavlja kljuĉ za razumevanje mehanizama probiotiĉkog dejstvalaktobacila. Savremena istraţivanja probiotiĉkih bakterija usmerena su ka identifikacijibiomolekula koji mogu modulisati razliĉite signalne puteve u humanim ćelijama. Svimolekuli koji su poreklom iz probiotika i odgovorni su za njihov pozitivan efekat nazdravlje domaćina nazvani su postbiotici. Zbog slabijeg imunostimulišućeg potencijala,njihova primena predstavlja bezbednu alternativu primeni ţivih bakterija.Ovo istraţivanje je imalo za cilj da testira mogućnost primene postbiotika uublaţavanju simptoma bola i neţeljenih efekata koji nastaju kao posledica primeneanalgetika. Taĉnije, definisana su dva specifiĉna cilja istraţivanja: (i) ispitati uticajbioaktivnih molekula odabranih sojeva laktobacila na proces autofagije u hepatocitima invitro, kao i protektivan efekat ovih molekula kod toksiĉnosti izazvane paracetamolom i (ii)ispitati potencijalni imunomodulatorni efekat egzopolisaharida (EPS-CG11) izolovanog izsoja Lactobacillus paraplantarum BGCG11, u in vivo eksperimentalnim modelimainflamacije. Eksperimenti u kulturi hepatocita ukljuĉili su praćenje stepena oštećenjaHepG2 ćelija izloţenih toksiĉnoj koncentraciji paracetamola i procesa autofagije, sa ciljemidentifikacije potencijalnog mehanizma delovanja postbiotika. Metodološki, vijabilnostHepG2 ćelija analizirana je MTT i LDH esejima. Autofagija je praćena Western blotanalizom odreĊivanjem ekspresije p62/SQSTM1 proteina i akumulacijom liposolubilneforme LC3 proteina. Dodatno, autofagija je analizirana praćenjem ekspresije BECN1, Atg5,p62/SQSTM1 i PINK1 gena i autofagnog fluksa. Za analizu imunomodulatornog efektaEPS-CG11 korišćena su dva in vivo modela inflamacije izazvane karageninom: modelinflamatornog bola i model peritonitisa kod pacova Wistar soja. U eksperimentuinflamatornog bola praćeni su: vremenski tok razvoja hiperalgezije i edema šapica nakonprofilaktiĉke sistemske primene EPS-CG11, ekspresija medijatora inflamacije (IL-1β,TNF-α, IL-6 i iNOS), infiltracija neutrofila (ekspresija MPO enzima) i aktivacija/infiltracijamonocita (ekspresija CD14 markera)...
AB  - Isolation and characterization of bacterial biomolecules involved in the interactionwith the receptors of the host cells represent the key factor for understanding themechanisms of probiotic action of lactobacilli. Novel studies regarding probiotic bacteriahave been focused on the identification of biomolecules which can modulate differentsignaling pathways in human cells. All molecules that originate from probiotics which areresponsible for its positive effects on the host’s health are called postbiotics. Theirapplication represents the safe alternative to the use of live bacteria and itsimmunostimulating potential.This research aimed to test the possibility of using postbiotics in alleviation of painsymptoms and analgesics side effects. More precisely, two main objectives of this researchwere: (i) to examine the influence of bioactive molecules of selected strains of lactobacillion the autophagy process in the hepatocytes, in vitro, as well as protective effect of thesemolecules in paracetamol-induced toxicity and (ii) to examine the potentialimmunomodulatory effect of exopolysaccharide (EPS-CG11) isolated from Lactobacillusparaplantarum BGCG11 strain, in in vivo experimental models of inflammation.Experiments in the hepatocytes culture included monitoring the degree of damage ofHepG2 cells exposed to the toxic paracetamol concentration and the autophagy process,with the aim of identification of potential mechanism of postbiotic action.Methodologically, the cell viability was monitored by MTT and LDH assays. Autophagywas monitored by Western blot analysis, in order to determine the expression of thep62/SQSTM1 protein and the accumulation of the liposoluble form of the LC3 protein.Further, the autophagy was analyzed by monitoring the expression of BECN1, Atg5,p62/SQSTM1 and PINK1 genes and the autophagy flux. For the analysis of theimmunomodulatory effect of EPS-CG11, two in vivo models of carrageenan-inducedinflammation were used: an inflammatory pain model and a peritonitis model in the Wistarrats...
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Uticaj bioaktivnih molekula laktobacila na procese autofagije i inflamacije u in vitro i in vivo sistemima
UR  - https://hdl.handle.net/21.15107/rcub_nardus_9986
ER  - 

@phdthesis{
author = "Dinić, Miroslav",
year = "2018",
abstract = "Izolacija i karakterizacija bakterijskih biomolekula koji interaguju sa receptorimaćelija domaćina predstavlja kljuĉ za razumevanje mehanizama probiotiĉkog dejstvalaktobacila. Savremena istraţivanja probiotiĉkih bakterija usmerena su ka identifikacijibiomolekula koji mogu modulisati razliĉite signalne puteve u humanim ćelijama. Svimolekuli koji su poreklom iz probiotika i odgovorni su za njihov pozitivan efekat nazdravlje domaćina nazvani su postbiotici. Zbog slabijeg imunostimulišućeg potencijala,njihova primena predstavlja bezbednu alternativu primeni ţivih bakterija.Ovo istraţivanje je imalo za cilj da testira mogućnost primene postbiotika uublaţavanju simptoma bola i neţeljenih efekata koji nastaju kao posledica primeneanalgetika. Taĉnije, definisana su dva specifiĉna cilja istraţivanja: (i) ispitati uticajbioaktivnih molekula odabranih sojeva laktobacila na proces autofagije u hepatocitima invitro, kao i protektivan efekat ovih molekula kod toksiĉnosti izazvane paracetamolom i (ii)ispitati potencijalni imunomodulatorni efekat egzopolisaharida (EPS-CG11) izolovanog izsoja Lactobacillus paraplantarum BGCG11, u in vivo eksperimentalnim modelimainflamacije. Eksperimenti u kulturi hepatocita ukljuĉili su praćenje stepena oštećenjaHepG2 ćelija izloţenih toksiĉnoj koncentraciji paracetamola i procesa autofagije, sa ciljemidentifikacije potencijalnog mehanizma delovanja postbiotika. Metodološki, vijabilnostHepG2 ćelija analizirana je MTT i LDH esejima. Autofagija je praćena Western blotanalizom odreĊivanjem ekspresije p62/SQSTM1 proteina i akumulacijom liposolubilneforme LC3 proteina. Dodatno, autofagija je analizirana praćenjem ekspresije BECN1, Atg5,p62/SQSTM1 i PINK1 gena i autofagnog fluksa. Za analizu imunomodulatornog efektaEPS-CG11 korišćena su dva in vivo modela inflamacije izazvane karageninom: modelinflamatornog bola i model peritonitisa kod pacova Wistar soja. U eksperimentuinflamatornog bola praćeni su: vremenski tok razvoja hiperalgezije i edema šapica nakonprofilaktiĉke sistemske primene EPS-CG11, ekspresija medijatora inflamacije (IL-1β,TNF-α, IL-6 i iNOS), infiltracija neutrofila (ekspresija MPO enzima) i aktivacija/infiltracijamonocita (ekspresija CD14 markera)..., Isolation and characterization of bacterial biomolecules involved in the interactionwith the receptors of the host cells represent the key factor for understanding themechanisms of probiotic action of lactobacilli. Novel studies regarding probiotic bacteriahave been focused on the identification of biomolecules which can modulate differentsignaling pathways in human cells. All molecules that originate from probiotics which areresponsible for its positive effects on the host’s health are called postbiotics. Theirapplication represents the safe alternative to the use of live bacteria and itsimmunostimulating potential.This research aimed to test the possibility of using postbiotics in alleviation of painsymptoms and analgesics side effects. More precisely, two main objectives of this researchwere: (i) to examine the influence of bioactive molecules of selected strains of lactobacillion the autophagy process in the hepatocytes, in vitro, as well as protective effect of thesemolecules in paracetamol-induced toxicity and (ii) to examine the potentialimmunomodulatory effect of exopolysaccharide (EPS-CG11) isolated from Lactobacillusparaplantarum BGCG11 strain, in in vivo experimental models of inflammation.Experiments in the hepatocytes culture included monitoring the degree of damage ofHepG2 cells exposed to the toxic paracetamol concentration and the autophagy process,with the aim of identification of potential mechanism of postbiotic action.Methodologically, the cell viability was monitored by MTT and LDH assays. Autophagywas monitored by Western blot analysis, in order to determine the expression of thep62/SQSTM1 protein and the accumulation of the liposoluble form of the LC3 protein.Further, the autophagy was analyzed by monitoring the expression of BECN1, Atg5,p62/SQSTM1 and PINK1 genes and the autophagy flux. For the analysis of theimmunomodulatory effect of EPS-CG11, two in vivo models of carrageenan-inducedinflammation were used: an inflammatory pain model and a peritonitis model in the Wistarrats...",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Uticaj bioaktivnih molekula laktobacila na procese autofagije i inflamacije u in vitro i in vivo sistemima",
url = "https://hdl.handle.net/21.15107/rcub_nardus_9986"
}

Dinić, M.. (2018). Uticaj bioaktivnih molekula laktobacila na procese autofagije i inflamacije u in vitro i in vivo sistemima. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_9986

Dinić M. Uticaj bioaktivnih molekula laktobacila na procese autofagije i inflamacije u in vitro i in vivo sistemima. in Универзитет у Београду. 2018;.
https://hdl.handle.net/21.15107/rcub_nardus_9986 .

Dinić, Miroslav, "Uticaj bioaktivnih molekula laktobacila na procese autofagije i inflamacije u in vitro i in vivo sistemima" in Универзитет у Београду (2018),
https://hdl.handle.net/21.15107/rcub_nardus_9986 .

TY  - JOUR
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Micov, Ana
AU  - Vučković, Sonja M.
AU  - Stepanović-Petrović, Radica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3122
AB  - Inflammatory pain is the most common type of pain that is treated clinically. The use of currently available treatments (classic analgesics - NSAID5, paracetamol and opioids) is limited by insufficient efficacy and/or side effects/ tolerance development. Antiepileptic drugs (AEDs) are widely used in neuropathic pain treatment, but there is substantial preclinical evidence on their efficacy against inflammatory pain, too. In this review we focus on gabapentinoids (gabapentin and pregabalin) and dibenzazepine AEDs (carbamazepine, oxcarbazepine, and recently introduced eslicarbazepine acetate) and their potential for relieving inflammatory pain. In models of somatic, visceral and trigeminal inflammatory pain, that have a translational value for inflammatory conditions in locomotor system, viscera and head/face, AEDs have demonstrated analgesic activity. This activity was mostly consistent, dependent on the dose and largely independent on the site of inflammation and method of its induction, nociceptive stimuli, species, specific drug used, its route of administration and dosing schedule. AEDs exerted comparable efficacy with classic analgesics. Effective doses of AEDs are lower than toxic doses in animals and, when expressed as equivalent human doses, they are largely overlapping with AEDs doses already used in humans for treating epilepsy/neuropathic pain. The main mechanism of antinociceptive/antihyperalgesic action of gabapentinoids in inflammatory pain models seems to be alpha 2 delta-dependent suppression of voltage -gated calcium channels in primary sensory neurons that leads to reduced release of neurotransmitters in the spinal/medullar dorsal horn. The suppression of NMDA receptors via co-agonist binding site primarily at spinal sites, activation of various types of K+ channels at spinal and peripheral sites, and activation of noradrenergic and serotonergic descending pain modulatory pathways may also contribute. Inhibition of voltage -gated sodium channels along the pain pathway is probably the main mechanism of antinociceptive/antihyperalgesic effects of dibenzazepines. The recruitment of peripheral adrenergic and purinergic mechanisms and central GABAergic mechanisms may also contribute. When co-administered with classic/other alternative analgesics, AEDs exerted synergistic/additive interactions. Reviewed data could serve as a basis for clinical studies on the efficacy/safety of AEDs as analgesics/adjuvants in patients with inflammatory pain, and contribute to the improvement of the treatment of various inflammatory pain states.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Pharmacology & Therapeutics
T1  - Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence
VL  - 192
SP  - 42
EP  - 64
DO  - 10.1016/j.pharmthera.2018.06.002
ER  - 

@article{
author = "Tomić, Maja and Pecikoza, Uroš and Micov, Ana and Vučković, Sonja M. and Stepanović-Petrović, Radica",
year = "2018",
abstract = "Inflammatory pain is the most common type of pain that is treated clinically. The use of currently available treatments (classic analgesics - NSAID5, paracetamol and opioids) is limited by insufficient efficacy and/or side effects/ tolerance development. Antiepileptic drugs (AEDs) are widely used in neuropathic pain treatment, but there is substantial preclinical evidence on their efficacy against inflammatory pain, too. In this review we focus on gabapentinoids (gabapentin and pregabalin) and dibenzazepine AEDs (carbamazepine, oxcarbazepine, and recently introduced eslicarbazepine acetate) and their potential for relieving inflammatory pain. In models of somatic, visceral and trigeminal inflammatory pain, that have a translational value for inflammatory conditions in locomotor system, viscera and head/face, AEDs have demonstrated analgesic activity. This activity was mostly consistent, dependent on the dose and largely independent on the site of inflammation and method of its induction, nociceptive stimuli, species, specific drug used, its route of administration and dosing schedule. AEDs exerted comparable efficacy with classic analgesics. Effective doses of AEDs are lower than toxic doses in animals and, when expressed as equivalent human doses, they are largely overlapping with AEDs doses already used in humans for treating epilepsy/neuropathic pain. The main mechanism of antinociceptive/antihyperalgesic action of gabapentinoids in inflammatory pain models seems to be alpha 2 delta-dependent suppression of voltage -gated calcium channels in primary sensory neurons that leads to reduced release of neurotransmitters in the spinal/medullar dorsal horn. The suppression of NMDA receptors via co-agonist binding site primarily at spinal sites, activation of various types of K+ channels at spinal and peripheral sites, and activation of noradrenergic and serotonergic descending pain modulatory pathways may also contribute. Inhibition of voltage -gated sodium channels along the pain pathway is probably the main mechanism of antinociceptive/antihyperalgesic effects of dibenzazepines. The recruitment of peripheral adrenergic and purinergic mechanisms and central GABAergic mechanisms may also contribute. When co-administered with classic/other alternative analgesics, AEDs exerted synergistic/additive interactions. Reviewed data could serve as a basis for clinical studies on the efficacy/safety of AEDs as analgesics/adjuvants in patients with inflammatory pain, and contribute to the improvement of the treatment of various inflammatory pain states.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Pharmacology & Therapeutics",
title = "Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence",
volume = "192",
pages = "42-64",
doi = "10.1016/j.pharmthera.2018.06.002"
}

Tomić, M., Pecikoza, U., Micov, A., Vučković, S. M.,& Stepanović-Petrović, R.. (2018). Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence. in Pharmacology & Therapeutics
Pergamon-Elsevier Science Ltd, Oxford., 192, 42-64.
https://doi.org/10.1016/j.pharmthera.2018.06.002

Tomić M, Pecikoza U, Micov A, Vučković SM, Stepanović-Petrović R. Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence. in Pharmacology & Therapeutics. 2018;192:42-64.
doi:10.1016/j.pharmthera.2018.06.002 .

Tomić, Maja, Pecikoza, Uroš, Micov, Ana, Vučković, Sonja M., Stepanović-Petrović, Radica, "Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence" in Pharmacology & Therapeutics, 192 (2018):42-64,
https://doi.org/10.1016/j.pharmthera.2018.06.002 . .

TY  - JOUR
AU  - Pecikoza, Uroš
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Stepanović-Petrović, Radica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3061
AB  - Aims: Eslicarbazepine acetate (ESL) is a novel dibenzazepine antiepileptic, that has demonstrated efficacy against trigeminal pain, both in preclinical and clinical studies. However, ESL's mechanism of antinociceptive action remains uncertain. Here, we aimed to examine the contribution of adrenergic/cholinergic/opioid receptors to the antinociceptive effects of ESL in a trigeminal pain model, as these neurotransmitter systems are known to have an important role in the modulation of trigeminal nociception. Main methods: ESL's effects in the orofacial formalin test were examined following peroral and local peripheral administration (subcutaneous, into the perinasal region). The involvement of adrenergic/cholinergic/opioid receptors was evaluated by intraperitoneally pretreating mice with an appropriate antagonist immediately after peroral application of ESL. We used antagonists of alpha(1)-adrenergic (prazosin), alpha(2)-adrenergic (yohimbine), beta(3)-adrenergic (non-selective, propranolol and beta(1)-selective, metoprolol), muscarinic (atropine), nicotinic (mecamylamine) and opioid receptors (naloxone). Additionally, the role of peripheral alpha(2)-adrenergic, beta(1)-adrenergic, muscarinic and opioid receptors was evaluated by co-injecting ESL with an antagonist into the perinasal area. Key findings: ESL dose-dependently reduced formalin-induced nociceptive behavior after systemic and local peripheral application. Systemic administration of yohimbine, propranolol, metoprolol, atropine and naloxone inhibited ESL's antinociceptive effects in a dose-related manner. Prazosin and mecamylamine did not produce inhibitory effects. Local application of yohimbine, atropine and naloxone into the perinasal area also produced a dose-related inhibition of ESL's efficacy, whereas metoprolol failed to inhibit the local antinociceptive effects of ESL. Significance: This study suggests that ESL's efficacy against trigeminal nociception is mediated by peripheral (and possibly central) alpha(2)-adrenergic, muscarinic and opioid receptors, as well as central beta(1)-adrenergic receptors.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Life Sciences
T1  - Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors
VL  - 214
SP  - 167
EP  - 175
DO  - 10.1016/j.lfs.2018.10.059
ER  - 

@article{
author = "Pecikoza, Uroš and Micov, Ana and Tomić, Maja and Stepanović-Petrović, Radica",
year = "2018",
abstract = "Aims: Eslicarbazepine acetate (ESL) is a novel dibenzazepine antiepileptic, that has demonstrated efficacy against trigeminal pain, both in preclinical and clinical studies. However, ESL's mechanism of antinociceptive action remains uncertain. Here, we aimed to examine the contribution of adrenergic/cholinergic/opioid receptors to the antinociceptive effects of ESL in a trigeminal pain model, as these neurotransmitter systems are known to have an important role in the modulation of trigeminal nociception. Main methods: ESL's effects in the orofacial formalin test were examined following peroral and local peripheral administration (subcutaneous, into the perinasal region). The involvement of adrenergic/cholinergic/opioid receptors was evaluated by intraperitoneally pretreating mice with an appropriate antagonist immediately after peroral application of ESL. We used antagonists of alpha(1)-adrenergic (prazosin), alpha(2)-adrenergic (yohimbine), beta(3)-adrenergic (non-selective, propranolol and beta(1)-selective, metoprolol), muscarinic (atropine), nicotinic (mecamylamine) and opioid receptors (naloxone). Additionally, the role of peripheral alpha(2)-adrenergic, beta(1)-adrenergic, muscarinic and opioid receptors was evaluated by co-injecting ESL with an antagonist into the perinasal area. Key findings: ESL dose-dependently reduced formalin-induced nociceptive behavior after systemic and local peripheral application. Systemic administration of yohimbine, propranolol, metoprolol, atropine and naloxone inhibited ESL's antinociceptive effects in a dose-related manner. Prazosin and mecamylamine did not produce inhibitory effects. Local application of yohimbine, atropine and naloxone into the perinasal area also produced a dose-related inhibition of ESL's efficacy, whereas metoprolol failed to inhibit the local antinociceptive effects of ESL. Significance: This study suggests that ESL's efficacy against trigeminal nociception is mediated by peripheral (and possibly central) alpha(2)-adrenergic, muscarinic and opioid receptors, as well as central beta(1)-adrenergic receptors.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Life Sciences",
title = "Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors",
volume = "214",
pages = "167-175",
doi = "10.1016/j.lfs.2018.10.059"
}

Pecikoza, U., Micov, A., Tomić, M.,& Stepanović-Petrović, R.. (2018). Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors. in Life Sciences
Pergamon-Elsevier Science Ltd, Oxford., 214, 167-175.
https://doi.org/10.1016/j.lfs.2018.10.059

Pecikoza U, Micov A, Tomić M, Stepanović-Petrović R. Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors. in Life Sciences. 2018;214:167-175.
doi:10.1016/j.lfs.2018.10.059 .

Pecikoza, Uroš, Micov, Ana, Tomić, Maja, Stepanović-Petrović, Radica, "Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors" in Life Sciences, 214 (2018):167-175,
https://doi.org/10.1016/j.lfs.2018.10.059 . .

TY  - JOUR
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Micov, Ana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3108
AB  - Pain is a symptom of most diseases that can significantly impair the patient's quality of life. In many diseases it is impossible to eliminate the cause of pain therefore the real goal of treatment is the removal of pain as a symptom, by application of analgesics. Contemporary pharmacotherapy employs conventional (opioid and non-opioid analgesics - NSAIDs and paracetamol) and adjuvant analgesics (antiepileptics, antidepressants and others). Analgesic effect of non-opioid analgesics is mainly the consequence of prostaglandin synthesis inhibition. They are effective for pain of mild/moderate intensity. In acute pain there is no difference in efficiency between NSAIDs and paracetamol, so the choice of the drug is individual. In chronic pain, when inflammation is present, NSAIDs are more effective than paracetamol. Long-term use of high doses of NSAIDs is often accompanied by side effects. In order to reduce their frequency, a careful assessment of risk for each patient should be made, a drug with a low risk of certain side effects should be chosen, the dose and duration of treatment should be limited and the possibility of topical application should be considered. The need for long-term use of NSAIDs should be reviewed periodically.
AB  - Bol je simptom većine oboljenja koji može značajno narušiti kvalitet života pacijenta. Kod mnogih oboljenja nemoguće je otkloniti uzrok bola, stoga je realni cilj lečenja uklanjanje bola kao simptoma, primenom analgetika. Savremena farmakoterapija raspolaže klasičnim (opioidni i ne-opiodini analgetici: NSAIL i paracetamol) i adjuvantnim analgeticima (antiepileptici, antidepresivi i drugi). Analgetičko dejstvo ne-opioidnih analgetika uglavnom je posledica inhibicije sinteze prostaglandina. Efikasni su kod bola blagog/umerenog intenziteta. Kod akutnog bola nema razlike u efikasnosti između NSAIL i paracetamola pa je izbor leka individualan. NSAIL su efikasniji kod hroničnih bolnih stanja u kojima je prisutna inflamacija, ali njihovu dugotrajnu primenu često prate neželjena dejstva. Kako bi se smanjila učestalost neželjenih efekata NSAIL, treba izvršiti pažljivu procenu rizika za svakog pacijenta, odabrati lek sa niskim rizikom za određeno neželjeno dejstvo, ograničiti dozu i trajanje tretmana i razmotriti mogućnost topikalne primene. Potrebu za dugotrajnom primenom NSAIL treba povremeno preispitivati.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Non-opioid analgesics in contemporary treatment of pain
T1  - Neopioidni analgetici u savremenom lečenju bola
VL  - 68
IS  - 6
SP  - 1021
EP  - 1031
DO  - 10.5937/ArhFarm1806021T
ER  - 

@article{
author = "Tomić, Maja and Pecikoza, Uroš and Micov, Ana",
year = "2018",
abstract = "Pain is a symptom of most diseases that can significantly impair the patient's quality of life. In many diseases it is impossible to eliminate the cause of pain therefore the real goal of treatment is the removal of pain as a symptom, by application of analgesics. Contemporary pharmacotherapy employs conventional (opioid and non-opioid analgesics - NSAIDs and paracetamol) and adjuvant analgesics (antiepileptics, antidepressants and others). Analgesic effect of non-opioid analgesics is mainly the consequence of prostaglandin synthesis inhibition. They are effective for pain of mild/moderate intensity. In acute pain there is no difference in efficiency between NSAIDs and paracetamol, so the choice of the drug is individual. In chronic pain, when inflammation is present, NSAIDs are more effective than paracetamol. Long-term use of high doses of NSAIDs is often accompanied by side effects. In order to reduce their frequency, a careful assessment of risk for each patient should be made, a drug with a low risk of certain side effects should be chosen, the dose and duration of treatment should be limited and the possibility of topical application should be considered. The need for long-term use of NSAIDs should be reviewed periodically., Bol je simptom većine oboljenja koji može značajno narušiti kvalitet života pacijenta. Kod mnogih oboljenja nemoguće je otkloniti uzrok bola, stoga je realni cilj lečenja uklanjanje bola kao simptoma, primenom analgetika. Savremena farmakoterapija raspolaže klasičnim (opioidni i ne-opiodini analgetici: NSAIL i paracetamol) i adjuvantnim analgeticima (antiepileptici, antidepresivi i drugi). Analgetičko dejstvo ne-opioidnih analgetika uglavnom je posledica inhibicije sinteze prostaglandina. Efikasni su kod bola blagog/umerenog intenziteta. Kod akutnog bola nema razlike u efikasnosti između NSAIL i paracetamola pa je izbor leka individualan. NSAIL su efikasniji kod hroničnih bolnih stanja u kojima je prisutna inflamacija, ali njihovu dugotrajnu primenu često prate neželjena dejstva. Kako bi se smanjila učestalost neželjenih efekata NSAIL, treba izvršiti pažljivu procenu rizika za svakog pacijenta, odabrati lek sa niskim rizikom za određeno neželjeno dejstvo, ograničiti dozu i trajanje tretmana i razmotriti mogućnost topikalne primene. Potrebu za dugotrajnom primenom NSAIL treba povremeno preispitivati.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Non-opioid analgesics in contemporary treatment of pain, Neopioidni analgetici u savremenom lečenju bola",
volume = "68",
number = "6",
pages = "1021-1031",
doi = "10.5937/ArhFarm1806021T"
}

Tomić, M., Pecikoza, U.,& Micov, A.. (2018). Non-opioid analgesics in contemporary treatment of pain. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 68(6), 1021-1031.
https://doi.org/10.5937/ArhFarm1806021T

Tomić M, Pecikoza U, Micov A. Non-opioid analgesics in contemporary treatment of pain. in Arhiv za farmaciju. 2018;68(6):1021-1031.
doi:10.5937/ArhFarm1806021T .

Tomić, Maja, Pecikoza, Uroš, Micov, Ana, "Non-opioid analgesics in contemporary treatment of pain" in Arhiv za farmaciju, 68, no. 6 (2018):1021-1031,
https://doi.org/10.5937/ArhFarm1806021T . .

TY  - JOUR
AU  - Popović, Višnja
AU  - Tomić, Maja
AU  - Stepanović-Petrović, Radica
AU  - Micov, Ana
AU  - Milenković, Marina
AU  - Petrović, Silvana
AU  - Ušjak, Ljuboš
AU  - Niketić, Marjan
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3026
AB  - Phenolic compounds and different biological activities of the dry MeOH extracts of the flowers and the herb (aerial parts without flowers) of Laserpitium zernyi HAYEK (Apiaceae) were investigated. The total phenolic contents in the extracts were determined spectrophotometrically using Folin-Ciocalteu reagent. In both extracts, apigenin, luteolin, their 7-O-glucosides, and chlorogenic acid were detected by HPLC. Identified phenolics were quantified in both extracts, except luteolin in L. zernyi herb extract. The extracts (p.o.) were tested for anti-edematous activity in a model of carrageenan (i.pl.) induced rat paw edema. Antioxidant activity of the extracts was assessed by FRAP assay and DPPH and OH radicals scavenging tests. Antimicrobial activity was investigated using broth microdilution test against five Gram-positive and three Gram-negative bacteria, as well as against two strains of Candida albicans. The polyphenol-richer flower extract exerted higher anti-edematous and antioxidant activities. The herb extract exhibited better antimicrobial effect against Micrococcus luteus, Enterococcus faecalis, Bacillus subtilis, and Pseudomonas aeruginosa, while against other tested microorganisms, the activity of both extracts was identical. Demonstrated biological activities of L. zernyi flower and herb extracts represent a good basis for their further investigation as potential new herbal medicinal raw materials.
PB  - Wiley-VCH Verlag GMBH, Weinheim
T2  - Chemistry & Biodiversity
T1  - Laserpitium zernyi Hayek Flower and Herb Extracts: Phenolic Compounds, and Anti-edematous, Antioxidant, and Antimicrobial Activities
VL  - 14
IS  - 5
DO  - 10.1002/cbdv.201600432
ER  - 

@article{
author = "Popović, Višnja and Tomić, Maja and Stepanović-Petrović, Radica and Micov, Ana and Milenković, Marina and Petrović, Silvana and Ušjak, Ljuboš and Niketić, Marjan",
year = "2017",
abstract = "Phenolic compounds and different biological activities of the dry MeOH extracts of the flowers and the herb (aerial parts without flowers) of Laserpitium zernyi HAYEK (Apiaceae) were investigated. The total phenolic contents in the extracts were determined spectrophotometrically using Folin-Ciocalteu reagent. In both extracts, apigenin, luteolin, their 7-O-glucosides, and chlorogenic acid were detected by HPLC. Identified phenolics were quantified in both extracts, except luteolin in L. zernyi herb extract. The extracts (p.o.) were tested for anti-edematous activity in a model of carrageenan (i.pl.) induced rat paw edema. Antioxidant activity of the extracts was assessed by FRAP assay and DPPH and OH radicals scavenging tests. Antimicrobial activity was investigated using broth microdilution test against five Gram-positive and three Gram-negative bacteria, as well as against two strains of Candida albicans. The polyphenol-richer flower extract exerted higher anti-edematous and antioxidant activities. The herb extract exhibited better antimicrobial effect against Micrococcus luteus, Enterococcus faecalis, Bacillus subtilis, and Pseudomonas aeruginosa, while against other tested microorganisms, the activity of both extracts was identical. Demonstrated biological activities of L. zernyi flower and herb extracts represent a good basis for their further investigation as potential new herbal medicinal raw materials.",
publisher = "Wiley-VCH Verlag GMBH, Weinheim",
journal = "Chemistry & Biodiversity",
title = "Laserpitium zernyi Hayek Flower and Herb Extracts: Phenolic Compounds, and Anti-edematous, Antioxidant, and Antimicrobial Activities",
volume = "14",
number = "5",
doi = "10.1002/cbdv.201600432"
}

Popović, V., Tomić, M., Stepanović-Petrović, R., Micov, A., Milenković, M., Petrović, S., Ušjak, L.,& Niketić, M.. (2017). Laserpitium zernyi Hayek Flower and Herb Extracts: Phenolic Compounds, and Anti-edematous, Antioxidant, and Antimicrobial Activities. in Chemistry & Biodiversity
Wiley-VCH Verlag GMBH, Weinheim., 14(5).
https://doi.org/10.1002/cbdv.201600432

Popović V, Tomić M, Stepanović-Petrović R, Micov A, Milenković M, Petrović S, Ušjak L, Niketić M. Laserpitium zernyi Hayek Flower and Herb Extracts: Phenolic Compounds, and Anti-edematous, Antioxidant, and Antimicrobial Activities. in Chemistry & Biodiversity. 2017;14(5).
doi:10.1002/cbdv.201600432 .

Popović, Višnja, Tomić, Maja, Stepanović-Petrović, Radica, Micov, Ana, Milenković, Marina, Petrović, Silvana, Ušjak, Ljuboš, Niketić, Marjan, "Laserpitium zernyi Hayek Flower and Herb Extracts: Phenolic Compounds, and Anti-edematous, Antioxidant, and Antimicrobial Activities" in Chemistry & Biodiversity, 14, no. 5 (2017),
https://doi.org/10.1002/cbdv.201600432 . .

TY  - JOUR
AU  - Stepanović-Petrović, Radica
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3023
AB  - Rationale We have reported that levetiracetam, a novel anticonvulsant with analgesic properties, synergizes with ibuprofen/aspirin/paracetamol in a model of diabetic painful neuropathy (DPN). Most guidelines recommend gabapentin, pregabalin, and duloxetine as first-or second-line agents for DPN. Objective We examined the effects of combination treatment of first-/second-line analgesics with levetiracetam in a model of DPN. Additionally, the levetiracetam's combinations with antioxidants, low dose of aspirin, coenzyme Q10, or alpha-lipoic acid were evaluated. Methods Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin. The antinociceptive effects of orally administered levetiracetam, gabapentin, pregabalin, duloxetine (acute treatment) and aspirin, coenzyme Q10, and alpha-lipoic acid (preventive 7-day treatment), as well as combinations of levetiracetam with individual drugs were examined in the tail-flick test. In combination experiments, the drugs were coadministered in fixed-dose fractions of single-drug ED50; the type of interaction was determined by isobolographic analysis. Results About 60-, 32-, 30-, 26-, 18-, and 6-fold reductions of doses of both drugs in levetiracetam combinations with pregabalin, gabapentin, coenzyme Q10, aspirin, duloxetine, and alpha-lipoic acid, respectively, were detected. Conclusions Combinations of levetiracetam with gabapentin/pregabalin/duloxetine that target different mechanisms/sites of action involved in DPN, as well as combinations of levetiracetam and low-dose aspirin/coenzyme Q10/alpha-lipoic acid that target underlying causes of DPN, produce marked synergistic interactions in reducing nociception in diabetic mice. This suggests that these combination treatments might be of great benefit for diabetic patients and should be explored further in clinical trials.
PB  - Springer, New York
T2  - QSAR & Combinatorial Science
T1  - Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model
VL  - 234
IS  - 11
SP  - 1781
EP  - 1794
DO  - 10.1007/s00213-017-4583-z
ER  - 

@article{
author = "Stepanović-Petrović, Radica and Micov, Ana and Tomić, Maja and Pecikoza, Uroš",
year = "2017",
abstract = "Rationale We have reported that levetiracetam, a novel anticonvulsant with analgesic properties, synergizes with ibuprofen/aspirin/paracetamol in a model of diabetic painful neuropathy (DPN). Most guidelines recommend gabapentin, pregabalin, and duloxetine as first-or second-line agents for DPN. Objective We examined the effects of combination treatment of first-/second-line analgesics with levetiracetam in a model of DPN. Additionally, the levetiracetam's combinations with antioxidants, low dose of aspirin, coenzyme Q10, or alpha-lipoic acid were evaluated. Methods Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin. The antinociceptive effects of orally administered levetiracetam, gabapentin, pregabalin, duloxetine (acute treatment) and aspirin, coenzyme Q10, and alpha-lipoic acid (preventive 7-day treatment), as well as combinations of levetiracetam with individual drugs were examined in the tail-flick test. In combination experiments, the drugs were coadministered in fixed-dose fractions of single-drug ED50; the type of interaction was determined by isobolographic analysis. Results About 60-, 32-, 30-, 26-, 18-, and 6-fold reductions of doses of both drugs in levetiracetam combinations with pregabalin, gabapentin, coenzyme Q10, aspirin, duloxetine, and alpha-lipoic acid, respectively, were detected. Conclusions Combinations of levetiracetam with gabapentin/pregabalin/duloxetine that target different mechanisms/sites of action involved in DPN, as well as combinations of levetiracetam and low-dose aspirin/coenzyme Q10/alpha-lipoic acid that target underlying causes of DPN, produce marked synergistic interactions in reducing nociception in diabetic mice. This suggests that these combination treatments might be of great benefit for diabetic patients and should be explored further in clinical trials.",
publisher = "Springer, New York",
journal = "QSAR & Combinatorial Science",
title = "Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model",
volume = "234",
number = "11",
pages = "1781-1794",
doi = "10.1007/s00213-017-4583-z"
}

Stepanović-Petrović, R., Micov, A., Tomić, M.,& Pecikoza, U.. (2017). Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model. in QSAR & Combinatorial Science
Springer, New York., 234(11), 1781-1794.
https://doi.org/10.1007/s00213-017-4583-z

Stepanović-Petrović R, Micov A, Tomić M, Pecikoza U. Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model. in QSAR & Combinatorial Science. 2017;234(11):1781-1794.
doi:10.1007/s00213-017-4583-z .

Stepanović-Petrović, Radica, Micov, Ana, Tomić, Maja, Pecikoza, Uroš, "Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model" in QSAR & Combinatorial Science, 234, no. 11 (2017):1781-1794,
https://doi.org/10.1007/s00213-017-4583-z . .

TY  - CHAP
AU  - Tomić, Maja
AU  - Micov, Ana
AU  - Pecikoza, Uroš
AU  - Stepanović-Petrović, Radica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2967
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world. They act via inhibition of cyclooxygenase (COX) isoenzymes. The combined analgesic, anti-inflammatory, and antipyretic effects make NSAIDs especially useful for symptomatic relief of painful inflammatory conditions and fever. They are used for treating musculoskeletal disorders (chronic, like osteoarthritis and rheumatoid arthritis, and acute, like acute gout and injuries), headaches, dental and postoperative pain, and dysmenorrhea, and aspirin also for prevention of cardiovascular events. NSAIDs may cause serious gastrointestinal, cardiovascular, and renal adverse effects, which may be prevented by performing risk assessments for each patient, choosing a NSAID with low risk for the particular side effect, and limiting its dosage and treatment duration. Gastroprotective agents are recommended for gastroduodenal ulcers prevention. Topical NSAIDs application offers a possibility for minimization of all systemic NSAIDs side effects, as well as drug-drug interactions. Evidence supports topical NSAIDs use in hands and knees osteoarthritis, and probably also in acute musculoskeletal pain. They can cause local skin irritation. Modified-release oral preparations improve patient compliance, and are especially important for short-acting NSAIDs. Topical modified-release preparations could improve efficacy and tolerability of NSAIDs topical treatment, and patient compliance.
PB  - Elsevier Inc.
T2  - Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs: Formulation Challenges a
T1  - Clinical Uses of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Potential Benefits of NSAIDs Modified-Release Preparations
SP  - 1
EP  - 29
DO  - 10.1016/B978-0-12-804017-1.00001-7
ER  - 

@inbook{
author = "Tomić, Maja and Micov, Ana and Pecikoza, Uroš and Stepanović-Petrović, Radica",
year = "2017",
abstract = "Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world. They act via inhibition of cyclooxygenase (COX) isoenzymes. The combined analgesic, anti-inflammatory, and antipyretic effects make NSAIDs especially useful for symptomatic relief of painful inflammatory conditions and fever. They are used for treating musculoskeletal disorders (chronic, like osteoarthritis and rheumatoid arthritis, and acute, like acute gout and injuries), headaches, dental and postoperative pain, and dysmenorrhea, and aspirin also for prevention of cardiovascular events. NSAIDs may cause serious gastrointestinal, cardiovascular, and renal adverse effects, which may be prevented by performing risk assessments for each patient, choosing a NSAID with low risk for the particular side effect, and limiting its dosage and treatment duration. Gastroprotective agents are recommended for gastroduodenal ulcers prevention. Topical NSAIDs application offers a possibility for minimization of all systemic NSAIDs side effects, as well as drug-drug interactions. Evidence supports topical NSAIDs use in hands and knees osteoarthritis, and probably also in acute musculoskeletal pain. They can cause local skin irritation. Modified-release oral preparations improve patient compliance, and are especially important for short-acting NSAIDs. Topical modified-release preparations could improve efficacy and tolerability of NSAIDs topical treatment, and patient compliance.",
publisher = "Elsevier Inc.",
journal = "Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs: Formulation Challenges a",
booktitle = "Clinical Uses of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Potential Benefits of NSAIDs Modified-Release Preparations",
pages = "1-29",
doi = "10.1016/B978-0-12-804017-1.00001-7"
}

Tomić, M., Micov, A., Pecikoza, U.,& Stepanović-Petrović, R.. (2017). Clinical Uses of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Potential Benefits of NSAIDs Modified-Release Preparations. in Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs: Formulation Challenges a
Elsevier Inc.., 1-29.
https://doi.org/10.1016/B978-0-12-804017-1.00001-7

Tomić M, Micov A, Pecikoza U, Stepanović-Petrović R. Clinical Uses of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Potential Benefits of NSAIDs Modified-Release Preparations. in Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs: Formulation Challenges a. 2017;:1-29.
doi:10.1016/B978-0-12-804017-1.00001-7 .

Tomić, Maja, Micov, Ana, Pecikoza, Uroš, Stepanović-Petrović, Radica, "Clinical Uses of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Potential Benefits of NSAIDs Modified-Release Preparations" in Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs: Formulation Challenges a (2017):1-29,
https://doi.org/10.1016/B978-0-12-804017-1.00001-7 . .

TY  - JOUR
AU  - Pecikoza, Uroš
AU  - Tomić, Maja
AU  - Micov, Ana
AU  - Stepanović-Petrović, Radica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2925
AB  - BACKGROUND: Metformin is a widely used and safe antidiabetic drug that has recently been shown to possess analgesic properties in models of inflammatory pain. Because various arthritic inflammatory disorders are highly prevalent in diabetic patients, we aimed to examine the type of interaction between metformin and several conventional and adjuvant analgesic drugs (ibuprofen, aspirin, tramadol, and pregabalin) in a rat model of somatic inflammatory hyperalgesia. METHODS: Inflammation of the rat hind paw was induced by an intraplantar injection of carrageenan (0.1 mL, 1%). The antihyperalgesic effects of metformin (intraperitoneally), analgesics (orally or intraperitoneally), and 2-drug metformin-analgesic combinations were assessed with an electronic Von Frey anesthesiometer, by measuring the change in paw withdrawal thresholds induced by carrageenan (n = 6 rats in drug/drug combination treated groups). First, we determined the doses of individual drugs needed to produce an antihyperalgesic effect of 50% (ED50 values). In combination experiments, drugs were coadministered in fixed-dose fractions (1/16, 1/8, 1/4, and 1/2) of their individual ED50 values and the type of interaction between components was determined by isobolographic analysis. RESULTS: Metformin (50-200 mg/kg)sign ificantlyand dose-dependently reduced carrageenan-induced hyperalgesia with a maximal antihyperalgesic effect (mean SEM) of 62 6% (all P  lt = .024). Ibuprofen (25-150 mg/kg), aspirin (100-400 mg/kg), tramadol (0.5-5 mg/kg), and pregabalin (2.5-20 mg/kg) also produced significant and dose-dependent antihyperalgesic effects (all P  lt = .042) of similar magnitude to metformin (the maximal antihyperalgesic effects were 73 +/- 4% for ibuprofen, 62 +/- 4.2% for aspirin, 69 +/- 5.9% for tramadol, and 56 +/- 3.9% for pregabalin). In combination experiments, administration of 2-drug metformin-analgesic combinations led to a significant and dose-dependent reduction of carrageenan-induced hyperalgesia (all P  lt = .027). The isobolographic analysis revealed that metformin interacted synergistically with the examined analgesics (experimental ED50 values of 2-drug combinations were significantly lower than theoretical additive ED50 values; all P  lt  .05) and that there was a similar, approximately 5-fold, reduction of doses of both drugs in all tested combinations. CONCLUSIONS:.Our results suggest that in patients who are already receiving metformin therapy, lower doses of ibuprofen/aspirin/tramadol/pregabalin might be sufficient for achieving satisfactory pain relief. Metformin-aspirin combination might be particularly useful because it may achieve multiple therapeutic goals (glucoregulation, pain relief, and cardioprotection).
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Anesthesia and Analgesia
T1  - Metformin Synergizes With Conventional and Adjuvant Analgesic Drugs to Reduce Inflammatory Hyperalgesia in Rats
VL  - 124
IS  - 4
SP  - 1317
EP  - 1329
DO  - 10.1213/ANE.0000000000001561
ER  - 

@article{
author = "Pecikoza, Uroš and Tomić, Maja and Micov, Ana and Stepanović-Petrović, Radica",
year = "2017",
abstract = "BACKGROUND: Metformin is a widely used and safe antidiabetic drug that has recently been shown to possess analgesic properties in models of inflammatory pain. Because various arthritic inflammatory disorders are highly prevalent in diabetic patients, we aimed to examine the type of interaction between metformin and several conventional and adjuvant analgesic drugs (ibuprofen, aspirin, tramadol, and pregabalin) in a rat model of somatic inflammatory hyperalgesia. METHODS: Inflammation of the rat hind paw was induced by an intraplantar injection of carrageenan (0.1 mL, 1%). The antihyperalgesic effects of metformin (intraperitoneally), analgesics (orally or intraperitoneally), and 2-drug metformin-analgesic combinations were assessed with an electronic Von Frey anesthesiometer, by measuring the change in paw withdrawal thresholds induced by carrageenan (n = 6 rats in drug/drug combination treated groups). First, we determined the doses of individual drugs needed to produce an antihyperalgesic effect of 50% (ED50 values). In combination experiments, drugs were coadministered in fixed-dose fractions (1/16, 1/8, 1/4, and 1/2) of their individual ED50 values and the type of interaction between components was determined by isobolographic analysis. RESULTS: Metformin (50-200 mg/kg)sign ificantlyand dose-dependently reduced carrageenan-induced hyperalgesia with a maximal antihyperalgesic effect (mean SEM) of 62 6% (all P  lt = .024). Ibuprofen (25-150 mg/kg), aspirin (100-400 mg/kg), tramadol (0.5-5 mg/kg), and pregabalin (2.5-20 mg/kg) also produced significant and dose-dependent antihyperalgesic effects (all P  lt = .042) of similar magnitude to metformin (the maximal antihyperalgesic effects were 73 +/- 4% for ibuprofen, 62 +/- 4.2% for aspirin, 69 +/- 5.9% for tramadol, and 56 +/- 3.9% for pregabalin). In combination experiments, administration of 2-drug metformin-analgesic combinations led to a significant and dose-dependent reduction of carrageenan-induced hyperalgesia (all P  lt = .027). The isobolographic analysis revealed that metformin interacted synergistically with the examined analgesics (experimental ED50 values of 2-drug combinations were significantly lower than theoretical additive ED50 values; all P  lt  .05) and that there was a similar, approximately 5-fold, reduction of doses of both drugs in all tested combinations. CONCLUSIONS:.Our results suggest that in patients who are already receiving metformin therapy, lower doses of ibuprofen/aspirin/tramadol/pregabalin might be sufficient for achieving satisfactory pain relief. Metformin-aspirin combination might be particularly useful because it may achieve multiple therapeutic goals (glucoregulation, pain relief, and cardioprotection).",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Anesthesia and Analgesia",
title = "Metformin Synergizes With Conventional and Adjuvant Analgesic Drugs to Reduce Inflammatory Hyperalgesia in Rats",
volume = "124",
number = "4",
pages = "1317-1329",
doi = "10.1213/ANE.0000000000001561"
}

Pecikoza, U., Tomić, M., Micov, A.,& Stepanović-Petrović, R.. (2017). Metformin Synergizes With Conventional and Adjuvant Analgesic Drugs to Reduce Inflammatory Hyperalgesia in Rats. in Anesthesia and Analgesia
Lippincott Williams & Wilkins, Philadelphia., 124(4), 1317-1329.
https://doi.org/10.1213/ANE.0000000000001561

Pecikoza U, Tomić M, Micov A, Stepanović-Petrović R. Metformin Synergizes With Conventional and Adjuvant Analgesic Drugs to Reduce Inflammatory Hyperalgesia in Rats. in Anesthesia and Analgesia. 2017;124(4):1317-1329.
doi:10.1213/ANE.0000000000001561 .

Pecikoza, Uroš, Tomić, Maja, Micov, Ana, Stepanović-Petrović, Radica, "Metformin Synergizes With Conventional and Adjuvant Analgesic Drugs to Reduce Inflammatory Hyperalgesia in Rats" in Anesthesia and Analgesia, 124, no. 4 (2017):1317-1329,
https://doi.org/10.1213/ANE.0000000000001561 . .

TY  - JOUR
AU  - Samardžić, Stevan
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Stepanović-Petrović, Radica
AU  - Maksimović, Zoran
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2691
AB  - Ethnopharmacological relevance: Meadowsweet (Filipendula ulmaria (L.) Maxim.), and dropwort (Filipendula vulgaris Moench) flowers are traditionally used to treat various ailments, including inflammatory conditions. The aim of the present study was to validate the aforementioned ethnomedicinal claim by assessing antihyperalgesic and antiedematous activities and toxicity of orally administered lyophilized flower infusions (LFIs) of F. ulmaria and F. vulgaris in experimental animals. Materials and methods: The phytochemical analysis of LFIs was performed by HPLC-DAD. Antihyperalgesic and antiedematous activities were estimated in a rat model of inflammation induced by intraplantar injection of carrageenan using Von Frey anesthesiometer and plethysmometer, respectively. Moreover, acute oral toxicity of LFIs in mice was evaluated by observing changes in animal behavior and mortality for a period of 14 days following the treatment. Results: HPLC-DAD analysis revealed the presence of phenolic acids and flavonoids in LFIs, among which spiraeoside was identified as the principal component (56.27 +/- 1.03 and 55.67 +/- 1.82 mg/g of LFI in F. ulmaria and F. vulgaris, respectively). The LFIs of F. ulmaria and F. vulgaris (100-300 mg/kg; p.o.) produced significant and dose-dependent antihyperalgesic effects: ED50 +/- SEM values were 164.8 +/- 15.4 mg/kg (110.3-246.3 mg/kg) and 172.2 +/- 6.2 mg/kg (147.4-201.3 mg/kg) for F. ulmaria and F. vulgaris, respectively. On the other hand, LFIs of both species (100-300 mg/kg; p.o.) did not significantly reduce edema. Good safety profiles were evidenced in the toxicological study. The median lethal dose (LD50) of the tested extracts is likely to be greater than 2000 mg/kg. Conclusion: The results of the present study support the use of F. ulmaria and F. vulgaris flowers in folk medicine for relieving pain in diseases with an inflammatory component.
PB  - Elsevier Ireland Ltd, Clare
T2  - Journal of Ethnopharmacology
T1  - Antihyperalgesic activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris Moench in a rat model of inflammation
VL  - 193
SP  - 652
EP  - 656
DO  - 10.1016/j.jep.2016.10.024
ER  - 

@article{
author = "Samardžić, Stevan and Tomić, Maja and Pecikoza, Uroš and Stepanović-Petrović, Radica and Maksimović, Zoran",
year = "2016",
abstract = "Ethnopharmacological relevance: Meadowsweet (Filipendula ulmaria (L.) Maxim.), and dropwort (Filipendula vulgaris Moench) flowers are traditionally used to treat various ailments, including inflammatory conditions. The aim of the present study was to validate the aforementioned ethnomedicinal claim by assessing antihyperalgesic and antiedematous activities and toxicity of orally administered lyophilized flower infusions (LFIs) of F. ulmaria and F. vulgaris in experimental animals. Materials and methods: The phytochemical analysis of LFIs was performed by HPLC-DAD. Antihyperalgesic and antiedematous activities were estimated in a rat model of inflammation induced by intraplantar injection of carrageenan using Von Frey anesthesiometer and plethysmometer, respectively. Moreover, acute oral toxicity of LFIs in mice was evaluated by observing changes in animal behavior and mortality for a period of 14 days following the treatment. Results: HPLC-DAD analysis revealed the presence of phenolic acids and flavonoids in LFIs, among which spiraeoside was identified as the principal component (56.27 +/- 1.03 and 55.67 +/- 1.82 mg/g of LFI in F. ulmaria and F. vulgaris, respectively). The LFIs of F. ulmaria and F. vulgaris (100-300 mg/kg; p.o.) produced significant and dose-dependent antihyperalgesic effects: ED50 +/- SEM values were 164.8 +/- 15.4 mg/kg (110.3-246.3 mg/kg) and 172.2 +/- 6.2 mg/kg (147.4-201.3 mg/kg) for F. ulmaria and F. vulgaris, respectively. On the other hand, LFIs of both species (100-300 mg/kg; p.o.) did not significantly reduce edema. Good safety profiles were evidenced in the toxicological study. The median lethal dose (LD50) of the tested extracts is likely to be greater than 2000 mg/kg. Conclusion: The results of the present study support the use of F. ulmaria and F. vulgaris flowers in folk medicine for relieving pain in diseases with an inflammatory component.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Journal of Ethnopharmacology",
title = "Antihyperalgesic activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris Moench in a rat model of inflammation",
volume = "193",
pages = "652-656",
doi = "10.1016/j.jep.2016.10.024"
}

Samardžić, S., Tomić, M., Pecikoza, U., Stepanović-Petrović, R.,& Maksimović, Z.. (2016). Antihyperalgesic activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris Moench in a rat model of inflammation. in Journal of Ethnopharmacology
Elsevier Ireland Ltd, Clare., 193, 652-656.
https://doi.org/10.1016/j.jep.2016.10.024

Samardžić S, Tomić M, Pecikoza U, Stepanović-Petrović R, Maksimović Z. Antihyperalgesic activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris Moench in a rat model of inflammation. in Journal of Ethnopharmacology. 2016;193:652-656.
doi:10.1016/j.jep.2016.10.024 .

Samardžić, Stevan, Tomić, Maja, Pecikoza, Uroš, Stepanović-Petrović, Radica, Maksimović, Zoran, "Antihyperalgesic activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris Moench in a rat model of inflammation" in Journal of Ethnopharmacology, 193 (2016):652-656,
https://doi.org/10.1016/j.jep.2016.10.024 . .

TY  - JOUR
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Ugrešić, Nenad
AU  - Stepanović-Petrović, Radica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2435
AB  - Painful diabetic neuropathy is difficult to treat. Single analgesics often have insufficient efficacy and poor tolerability. Combination therapy may therefore be of particular benefit, because it might provide optimal analgesia with fewer adverse effects. This study aimed to examine the type of interaction between levetiracetam, a novel anticonvulsant with analgesic properties, and commonly used analgesics (ibuprofen, aspirin and paracetamol) in a mouse model of painful diabetic neuropathy. Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin, applied intraperitoneally (150 mg/kg). Thermal (tail-flick test) and mechanical (electronic von Frey test) nociceptive thresholds were measured before and three weeks after diabetes induction. The antinociceptive effects of orally administered levetiracetam, analgesics, and their combinations were examined in diabetic mice that developed thermal/mechanical hypersensitivity. In combination experiments, the drugs were co-administered in fixed-dose fractions of single drug ED50 and the type of interaction was determined by isobolographic analysis. Levetiracetam (10-100 mg/kg), ibuprofen (2-50 mg/kg), aspirin (5-75 mg/kg), paracetamol (5-100 mg/kg), and levetiracetam-analgesic combinations produced significant, dose-dependent antinociceptive effects in diabetic mice in both tests. In the tail-flick test, isobolographic analysis revealed 15-, and 19-fold reduction of doses of both drugs in the combination of levetiracetam with aspirin/ibuprofen, and paracetamol, respectively. In the von Frey test, approximately 7- and 9-fold reduction of doses of both drugs was detected in levetiracetam-ibuprofen and levetiracetam-aspirin/levetiracetam-paracetamol combinations, respectively. These results show synergism between levetiracetam and ibuprofen/aspirin/paracetamol in a model of painful diabetic neuropathy and might provide a useful approach to the treatment of patients suffering from painful diabetic neuropathy.
PB  - Academic Press Ltd- Elsevier Science Ltd, London
T2  - Pharmacological Research
T1  - Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy
VL  - 97
SP  - 131
EP  - 142
DO  - 10.1016/j.phrs.2015.04.014
ER  - 

@article{
author = "Micov, Ana and Tomić, Maja and Pecikoza, Uroš and Ugrešić, Nenad and Stepanović-Petrović, Radica",
year = "2015",
abstract = "Painful diabetic neuropathy is difficult to treat. Single analgesics often have insufficient efficacy and poor tolerability. Combination therapy may therefore be of particular benefit, because it might provide optimal analgesia with fewer adverse effects. This study aimed to examine the type of interaction between levetiracetam, a novel anticonvulsant with analgesic properties, and commonly used analgesics (ibuprofen, aspirin and paracetamol) in a mouse model of painful diabetic neuropathy. Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin, applied intraperitoneally (150 mg/kg). Thermal (tail-flick test) and mechanical (electronic von Frey test) nociceptive thresholds were measured before and three weeks after diabetes induction. The antinociceptive effects of orally administered levetiracetam, analgesics, and their combinations were examined in diabetic mice that developed thermal/mechanical hypersensitivity. In combination experiments, the drugs were co-administered in fixed-dose fractions of single drug ED50 and the type of interaction was determined by isobolographic analysis. Levetiracetam (10-100 mg/kg), ibuprofen (2-50 mg/kg), aspirin (5-75 mg/kg), paracetamol (5-100 mg/kg), and levetiracetam-analgesic combinations produced significant, dose-dependent antinociceptive effects in diabetic mice in both tests. In the tail-flick test, isobolographic analysis revealed 15-, and 19-fold reduction of doses of both drugs in the combination of levetiracetam with aspirin/ibuprofen, and paracetamol, respectively. In the von Frey test, approximately 7- and 9-fold reduction of doses of both drugs was detected in levetiracetam-ibuprofen and levetiracetam-aspirin/levetiracetam-paracetamol combinations, respectively. These results show synergism between levetiracetam and ibuprofen/aspirin/paracetamol in a model of painful diabetic neuropathy and might provide a useful approach to the treatment of patients suffering from painful diabetic neuropathy.",
publisher = "Academic Press Ltd- Elsevier Science Ltd, London",
journal = "Pharmacological Research",
title = "Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy",
volume = "97",
pages = "131-142",
doi = "10.1016/j.phrs.2015.04.014"
}

Micov, A., Tomić, M., Pecikoza, U., Ugrešić, N.,& Stepanović-Petrović, R.. (2015). Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy. in Pharmacological Research
Academic Press Ltd- Elsevier Science Ltd, London., 97, 131-142.
https://doi.org/10.1016/j.phrs.2015.04.014

Micov A, Tomić M, Pecikoza U, Ugrešić N, Stepanović-Petrović R. Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy. in Pharmacological Research. 2015;97:131-142.
doi:10.1016/j.phrs.2015.04.014 .

Micov, Ana, Tomić, Maja, Pecikoza, Uroš, Ugrešić, Nenad, Stepanović-Petrović, Radica, "Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy" in Pharmacological Research, 97 (2015):131-142,
https://doi.org/10.1016/j.phrs.2015.04.014 . .

TY  - JOUR
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Micov, Ana
AU  - Popović, Božidar V.
AU  - Stepanović-Petrović, Radica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2385
AB  - BACKGROUND: Levetiracetam is an antiepileptic drug with analgesic efficacy shown in pain models and small clinical trials. Sumatriptan is used in acute migraine treatment. Caffeine is widely consumed in some beverages/foods and is also an adjuvant in analgesic formulations. We examined the effects of systemic levetiracetam, sumatriptan, and caffeine and their interactions in 2-component combinations in the rat orofacial formalin test, a model of trigeminal pain. METHODS: Rats received a subcutaneous injection of formalin solution into the perinasal area, and the total time spent in nociceptive behavior (face rubbing) was quantified. The antinociceptive effect of drugs/drug combinations was assessed 1 hour after per os administration. The type of interaction between levetiracetam/sumatriptan and caffeine was examined by comparing the effects of a fixed, effective dose of levetiracetam/sumatriptan alone with the effects of the same dose applied with increasing, subeffective doses of caffeine. The type of interaction between levetiracetam and sumatriptan was determined by isobolographic analysis. RESULTS: Levetiracetam (1-50 mg/kg) and sumatriptan (0.5-5 mg/kg) produced significant and dose-dependent antinociceptive effects in both phases of the orofacial formalin test (P = 0.001). Caffeine (7.5-100 mg/kg) produced significant antinociception in the second phase of the test (P = 0.04). Caffeine (1-7.5 mg/kg) significantly reduced the antinociceptive effects of levetiracetam (25 mg/kg) (first phase P = 0.002, second phase P  lt  0.001) and sumatriptan (2.5 mg/kg) (first phase P = 0.014, second phase P = 0.027); dose-dependent inhibition was observed in the second phase. Levetiracetam and sumatriptan exerted an additive interaction in the second phase of the orofacial formalin test. CONCLUSIONS: Results indicate that levetiracetam may be useful for treatment of pain in the trigeminal region. Dietary caffeine might decrease the effects of levetiracetam and sumatriptan; this needs to be considered in clinical settings. A levetiracetam-sumatriptan combination could also be useful in trigeminal pain treatment. Its efficacy and adverse effects should be examined clinically.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Anesthesia and Analgesia
T1  - The Effects of Levetiracetam, Sumatriptan, and Caffeine in a Rat Model of Trigeminal Pain: Interactions in 2-Component Combinations
VL  - 120
IS  - 6
SP  - 1385
EP  - 1393
DO  - 10.1213/ANE.0000000000000640
ER  - 

@article{
author = "Tomić, Maja and Pecikoza, Uroš and Micov, Ana and Popović, Božidar V. and Stepanović-Petrović, Radica",
year = "2015",
abstract = "BACKGROUND: Levetiracetam is an antiepileptic drug with analgesic efficacy shown in pain models and small clinical trials. Sumatriptan is used in acute migraine treatment. Caffeine is widely consumed in some beverages/foods and is also an adjuvant in analgesic formulations. We examined the effects of systemic levetiracetam, sumatriptan, and caffeine and their interactions in 2-component combinations in the rat orofacial formalin test, a model of trigeminal pain. METHODS: Rats received a subcutaneous injection of formalin solution into the perinasal area, and the total time spent in nociceptive behavior (face rubbing) was quantified. The antinociceptive effect of drugs/drug combinations was assessed 1 hour after per os administration. The type of interaction between levetiracetam/sumatriptan and caffeine was examined by comparing the effects of a fixed, effective dose of levetiracetam/sumatriptan alone with the effects of the same dose applied with increasing, subeffective doses of caffeine. The type of interaction between levetiracetam and sumatriptan was determined by isobolographic analysis. RESULTS: Levetiracetam (1-50 mg/kg) and sumatriptan (0.5-5 mg/kg) produced significant and dose-dependent antinociceptive effects in both phases of the orofacial formalin test (P = 0.001). Caffeine (7.5-100 mg/kg) produced significant antinociception in the second phase of the test (P = 0.04). Caffeine (1-7.5 mg/kg) significantly reduced the antinociceptive effects of levetiracetam (25 mg/kg) (first phase P = 0.002, second phase P  lt  0.001) and sumatriptan (2.5 mg/kg) (first phase P = 0.014, second phase P = 0.027); dose-dependent inhibition was observed in the second phase. Levetiracetam and sumatriptan exerted an additive interaction in the second phase of the orofacial formalin test. CONCLUSIONS: Results indicate that levetiracetam may be useful for treatment of pain in the trigeminal region. Dietary caffeine might decrease the effects of levetiracetam and sumatriptan; this needs to be considered in clinical settings. A levetiracetam-sumatriptan combination could also be useful in trigeminal pain treatment. Its efficacy and adverse effects should be examined clinically.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Anesthesia and Analgesia",
title = "The Effects of Levetiracetam, Sumatriptan, and Caffeine in a Rat Model of Trigeminal Pain: Interactions in 2-Component Combinations",
volume = "120",
number = "6",
pages = "1385-1393",
doi = "10.1213/ANE.0000000000000640"
}

Tomić, M., Pecikoza, U., Micov, A., Popović, B. V.,& Stepanović-Petrović, R.. (2015). The Effects of Levetiracetam, Sumatriptan, and Caffeine in a Rat Model of Trigeminal Pain: Interactions in 2-Component Combinations. in Anesthesia and Analgesia
Lippincott Williams & Wilkins, Philadelphia., 120(6), 1385-1393.
https://doi.org/10.1213/ANE.0000000000000640

Tomić M, Pecikoza U, Micov A, Popović BV, Stepanović-Petrović R. The Effects of Levetiracetam, Sumatriptan, and Caffeine in a Rat Model of Trigeminal Pain: Interactions in 2-Component Combinations. in Anesthesia and Analgesia. 2015;120(6):1385-1393.
doi:10.1213/ANE.0000000000000640 .

Tomić, Maja, Pecikoza, Uroš, Micov, Ana, Popović, Božidar V., Stepanović-Petrović, Radica, "The Effects of Levetiracetam, Sumatriptan, and Caffeine in a Rat Model of Trigeminal Pain: Interactions in 2-Component Combinations" in Anesthesia and Analgesia, 120, no. 6 (2015):1385-1393,
https://doi.org/10.1213/ANE.0000000000000640 . .

TY  - JOUR
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Micov, Ana
AU  - Stepanović-Petrović, Radica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2304
AB  - BACKGROUND: Many clinical pain states that are difficult to treat share a common feature of sensitization of nociceptive pathways. Drugs that could normalize hyperexcitable neural activity (e.g., antiepileptic drugs) may be useful in relieving these pain states. Eslicarbazepine acetate (ESL) is a novel antiepileptic drug derived from carbamazepine/oxcarbazepine with a more favorable metabolic profile and potentially better tolerability. We examined the efficacy of ESL in models of inflammatory and neuropathic pain and the potential mechanism involved in its action. METHODS: The antinociceptive effects of ESL were assessed in mice models of trigeminal (orofacial formalin test), neuropathic (streptozotocin-induced diabetic neuropathy model), and visceral pain (writhing test). The influence of 5-HT1B/1D serotonin receptor (GR 127935) and CB1 (AM251) and CB2 cannabinoid receptor (AM630) antagonists on the antinociceptive effect of ESL was tested in the model of trigeminal pain. RESULTS: ESL exhibited significant and dose-dependent antinociceptive effects in the second phase of the orofacial formalin test (P 0.011), in the tail-flick test in diabetic mice (P 0.013), and in the writhing test (P 0.003). GR 127935 (P 0.038) and AM251 and AM630 (P 0.013 for both antagonists) significantly inhibited the antinociceptive effect of ESL in a dose-related manner. CONCLUSIONS: ESL exhibited efficacy in models of trigeminal, neuropathic, and visceral pain. In the trigeminal pain model, the antinociceptive effect of ESL is, at least in part, mediated by 5-HT1B/1D serotonin and CB1/CB2 cannabinoid receptors. This study indicates that ESL could be useful in the clinical treatment of inflammatory and neuropathic pain.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Anesthesia and Analgesia
T1  - The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors
VL  - 121
IS  - 6
SP  - 1632
EP  - 1639
DO  - 10.1213/ANE.0000000000000953
ER  - 

@article{
author = "Tomić, Maja and Pecikoza, Uroš and Micov, Ana and Stepanović-Petrović, Radica",
year = "2015",
abstract = "BACKGROUND: Many clinical pain states that are difficult to treat share a common feature of sensitization of nociceptive pathways. Drugs that could normalize hyperexcitable neural activity (e.g., antiepileptic drugs) may be useful in relieving these pain states. Eslicarbazepine acetate (ESL) is a novel antiepileptic drug derived from carbamazepine/oxcarbazepine with a more favorable metabolic profile and potentially better tolerability. We examined the efficacy of ESL in models of inflammatory and neuropathic pain and the potential mechanism involved in its action. METHODS: The antinociceptive effects of ESL were assessed in mice models of trigeminal (orofacial formalin test), neuropathic (streptozotocin-induced diabetic neuropathy model), and visceral pain (writhing test). The influence of 5-HT1B/1D serotonin receptor (GR 127935) and CB1 (AM251) and CB2 cannabinoid receptor (AM630) antagonists on the antinociceptive effect of ESL was tested in the model of trigeminal pain. RESULTS: ESL exhibited significant and dose-dependent antinociceptive effects in the second phase of the orofacial formalin test (P 0.011), in the tail-flick test in diabetic mice (P 0.013), and in the writhing test (P 0.003). GR 127935 (P 0.038) and AM251 and AM630 (P 0.013 for both antagonists) significantly inhibited the antinociceptive effect of ESL in a dose-related manner. CONCLUSIONS: ESL exhibited efficacy in models of trigeminal, neuropathic, and visceral pain. In the trigeminal pain model, the antinociceptive effect of ESL is, at least in part, mediated by 5-HT1B/1D serotonin and CB1/CB2 cannabinoid receptors. This study indicates that ESL could be useful in the clinical treatment of inflammatory and neuropathic pain.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Anesthesia and Analgesia",
title = "The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors",
volume = "121",
number = "6",
pages = "1632-1639",
doi = "10.1213/ANE.0000000000000953"
}

Tomić, M., Pecikoza, U., Micov, A.,& Stepanović-Petrović, R.. (2015). The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors. in Anesthesia and Analgesia
Lippincott Williams & Wilkins, Philadelphia., 121(6), 1632-1639.
https://doi.org/10.1213/ANE.0000000000000953

Tomić M, Pecikoza U, Micov A, Stepanović-Petrović R. The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors. in Anesthesia and Analgesia. 2015;121(6):1632-1639.
doi:10.1213/ANE.0000000000000953 .

Tomić, Maja, Pecikoza, Uroš, Micov, Ana, Stepanović-Petrović, Radica, "The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors" in Anesthesia and Analgesia, 121, no. 6 (2015):1632-1639,
https://doi.org/10.1213/ANE.0000000000000953 . .

TY  - JOUR
AU  - Tomić, Maja
AU  - Popović, Višnja
AU  - Petrović, Silvana
AU  - Stepanović-Petrović, Radica
AU  - Micov, Ana
AU  - Drobac, Milica
AU  - Couladis, Maria
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2234
AB  - From the dried flower heads of Matricaria recutita L., essential oil was isolated by hydrodistillation, and in the obtained blue oil, -bisabolol oxide A (21.5%), -bisabolol oxide B (25.5%) and (Z)-spiroether (cis-en-yn-spiroether) (10.3%) were identified as the main compounds, by gas chromatography (GC) and GC-mass spectrometry analyses. The antihyperalgesic effects of this oil were examined in a rat model of inflammation induced by carrageenan, through a modified paw-pressure' test. Antiedematous effects were examined in a rat model of inflammation induced by carrageenan, dextran and histamine, through plethysmometry. Matricaria oil (25, 50 and 100mg/kg, p.o.) exhibited a significant dose-dependent reduction of hyperalgesia and edema induced by carrageenan in both prophylactic and therapeutic treatment schemes. It was more efficacious in the prophylactic treatment scheme, and the corresponding median effective dose (ED50)+/- standard error of the mean (SEM) values were 49.8 +/- 6.0 and 42.4 +/- 0.2mg/kg for antihyperalgesic and antiedematous effects, respectively. Prophylactic treatments with matricaria oil (25, 50 and 100mg/kg, p.o.) caused a significant dose-dependent antiedematous effect in dextran-induced edema with lower efficacy than in the carrageenan model. In a dose of 100mg/kg, p.o., matricaria oil caused a slight reduction of histamine-induced edema. These results suggest that bisabolol-oxide-rich matricaria oil may be effective against pain and edema present in various inflammatory conditions, which supports matricaria traditional uses. Copyright
PB  - Wiley-Blackwell, Hoboken
T2  - Phytotherapy Research
T1  - Antihyperalgesic and Antiedematous Activities of Bisabolol-Oxides-Rich Matricaria Oil in a Rat Model of Inflammation
VL  - 28
IS  - 5
SP  - 759
EP  - 766
DO  - 10.1002/ptr.5057
ER  - 

@article{
author = "Tomić, Maja and Popović, Višnja and Petrović, Silvana and Stepanović-Petrović, Radica and Micov, Ana and Drobac, Milica and Couladis, Maria",
year = "2014",
abstract = "From the dried flower heads of Matricaria recutita L., essential oil was isolated by hydrodistillation, and in the obtained blue oil, -bisabolol oxide A (21.5%), -bisabolol oxide B (25.5%) and (Z)-spiroether (cis-en-yn-spiroether) (10.3%) were identified as the main compounds, by gas chromatography (GC) and GC-mass spectrometry analyses. The antihyperalgesic effects of this oil were examined in a rat model of inflammation induced by carrageenan, through a modified paw-pressure' test. Antiedematous effects were examined in a rat model of inflammation induced by carrageenan, dextran and histamine, through plethysmometry. Matricaria oil (25, 50 and 100mg/kg, p.o.) exhibited a significant dose-dependent reduction of hyperalgesia and edema induced by carrageenan in both prophylactic and therapeutic treatment schemes. It was more efficacious in the prophylactic treatment scheme, and the corresponding median effective dose (ED50)+/- standard error of the mean (SEM) values were 49.8 +/- 6.0 and 42.4 +/- 0.2mg/kg for antihyperalgesic and antiedematous effects, respectively. Prophylactic treatments with matricaria oil (25, 50 and 100mg/kg, p.o.) caused a significant dose-dependent antiedematous effect in dextran-induced edema with lower efficacy than in the carrageenan model. In a dose of 100mg/kg, p.o., matricaria oil caused a slight reduction of histamine-induced edema. These results suggest that bisabolol-oxide-rich matricaria oil may be effective against pain and edema present in various inflammatory conditions, which supports matricaria traditional uses. Copyright",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Phytotherapy Research",
title = "Antihyperalgesic and Antiedematous Activities of Bisabolol-Oxides-Rich Matricaria Oil in a Rat Model of Inflammation",
volume = "28",
number = "5",
pages = "759-766",
doi = "10.1002/ptr.5057"
}

Tomić, M., Popović, V., Petrović, S., Stepanović-Petrović, R., Micov, A., Drobac, M.,& Couladis, M.. (2014). Antihyperalgesic and Antiedematous Activities of Bisabolol-Oxides-Rich Matricaria Oil in a Rat Model of Inflammation. in Phytotherapy Research
Wiley-Blackwell, Hoboken., 28(5), 759-766.
https://doi.org/10.1002/ptr.5057

Tomić M, Popović V, Petrović S, Stepanović-Petrović R, Micov A, Drobac M, Couladis M. Antihyperalgesic and Antiedematous Activities of Bisabolol-Oxides-Rich Matricaria Oil in a Rat Model of Inflammation. in Phytotherapy Research. 2014;28(5):759-766.
doi:10.1002/ptr.5057 .

Tomić, Maja, Popović, Višnja, Petrović, Silvana, Stepanović-Petrović, Radica, Micov, Ana, Drobac, Milica, Couladis, Maria, "Antihyperalgesic and Antiedematous Activities of Bisabolol-Oxides-Rich Matricaria Oil in a Rat Model of Inflammation" in Phytotherapy Research, 28, no. 5 (2014):759-766,
https://doi.org/10.1002/ptr.5057 . .

TY  - JOUR
AU  - Popović, Višnja
AU  - Petrović, Silvana
AU  - Tomić, Maja
AU  - Stepanović-Petrović, Radica
AU  - Micov, Ana
AU  - Drobac, Milica
AU  - Couladis, Maria
AU  - Niketić, Marjan
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2167
AB  - In this paper antinociceptive and anti-edematous effects are examined of the essential oils of the underground parts of two Balkan endemic Laserpitium species (Apiaceae), L. zernyi and L. ochridanum. Furthermore, the essential oil of the underground parts of L. ochridanum is chemically characterised by GC and GC-MS. Antinociceptive and anti-edematous effects were measured in a rat model of localized inflammation, induced by carrageenan, using apparatus for the modified paw-pressure test, and plethysmometer, respectively. The effects of both Laserpitium essential oils were measured after oral gavage administration to male Wistar rats in doses of 25, 50 and 100 mg/kg. The main constituents of L. ochridanum essential oil were: alpha-pinene (33.2%), alpha-bisabolol (10.3%) and chamazulene (14.9%). The essential oil of L. zernyi was previously shown to be rich in alpha-pinene (31.6%) and alpha-bisabolol (30.9%). Both examined essential oils produced a significant dose-dependent antinociceptive effect. The corresponding ED50 +/- SEM in producing antinociception were 45.9 +/- 4.9 mg/kg and 42.4 +/- 2.1 mg/kg for L. zernyi and L. ochridanum oil, respectively. Both essential oils also significantly reduced paw edema in a dose-dependent manner. The estimated ED50 +/- SEM values for the anti-edematous effect were 36.3 +/- 4.5 mg/kg for L. zernyi oil and 45.1 +/- 11.3 mg/kg for L. ochridanum oil. These results suggest that the essential oils of both investigated Laserpitium species may be effective against pain and edema present in various inflammatory conditions.
PB  - Natural Products Inc, Westerville
T2  - Natural Product Communications
T1  - Antinociceptive and Anti-edematous Activities of the Essential Oils of Two Balkan Endemic Laserpitium Species
VL  - 9
IS  - 1
SP  - 125
EP  - 128
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2167
ER  - 

@article{
author = "Popović, Višnja and Petrović, Silvana and Tomić, Maja and Stepanović-Petrović, Radica and Micov, Ana and Drobac, Milica and Couladis, Maria and Niketić, Marjan",
year = "2014",
abstract = "In this paper antinociceptive and anti-edematous effects are examined of the essential oils of the underground parts of two Balkan endemic Laserpitium species (Apiaceae), L. zernyi and L. ochridanum. Furthermore, the essential oil of the underground parts of L. ochridanum is chemically characterised by GC and GC-MS. Antinociceptive and anti-edematous effects were measured in a rat model of localized inflammation, induced by carrageenan, using apparatus for the modified paw-pressure test, and plethysmometer, respectively. The effects of both Laserpitium essential oils were measured after oral gavage administration to male Wistar rats in doses of 25, 50 and 100 mg/kg. The main constituents of L. ochridanum essential oil were: alpha-pinene (33.2%), alpha-bisabolol (10.3%) and chamazulene (14.9%). The essential oil of L. zernyi was previously shown to be rich in alpha-pinene (31.6%) and alpha-bisabolol (30.9%). Both examined essential oils produced a significant dose-dependent antinociceptive effect. The corresponding ED50 +/- SEM in producing antinociception were 45.9 +/- 4.9 mg/kg and 42.4 +/- 2.1 mg/kg for L. zernyi and L. ochridanum oil, respectively. Both essential oils also significantly reduced paw edema in a dose-dependent manner. The estimated ED50 +/- SEM values for the anti-edematous effect were 36.3 +/- 4.5 mg/kg for L. zernyi oil and 45.1 +/- 11.3 mg/kg for L. ochridanum oil. These results suggest that the essential oils of both investigated Laserpitium species may be effective against pain and edema present in various inflammatory conditions.",
publisher = "Natural Products Inc, Westerville",
journal = "Natural Product Communications",
title = "Antinociceptive and Anti-edematous Activities of the Essential Oils of Two Balkan Endemic Laserpitium Species",
volume = "9",
number = "1",
pages = "125-128",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2167"
}

Popović, V., Petrović, S., Tomić, M., Stepanović-Petrović, R., Micov, A., Drobac, M., Couladis, M.,& Niketić, M.. (2014). Antinociceptive and Anti-edematous Activities of the Essential Oils of Two Balkan Endemic Laserpitium Species. in Natural Product Communications
Natural Products Inc, Westerville., 9(1), 125-128.
https://hdl.handle.net/21.15107/rcub_farfar_2167

Popović V, Petrović S, Tomić M, Stepanović-Petrović R, Micov A, Drobac M, Couladis M, Niketić M. Antinociceptive and Anti-edematous Activities of the Essential Oils of Two Balkan Endemic Laserpitium Species. in Natural Product Communications. 2014;9(1):125-128.
https://hdl.handle.net/21.15107/rcub_farfar_2167 .

Popović, Višnja, Petrović, Silvana, Tomić, Maja, Stepanović-Petrović, Radica, Micov, Ana, Drobac, Milica, Couladis, Maria, Niketić, Marjan, "Antinociceptive and Anti-edematous Activities of the Essential Oils of Two Balkan Endemic Laserpitium Species" in Natural Product Communications, 9, no. 1 (2014):125-128,
https://hdl.handle.net/21.15107/rcub_farfar_2167 .