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51. Evaluation of the stimulatory effect of Epimedium alpinum L. methanolic extract on the immune response in vivo

Author

Colić, M., Došlov-Kokoruš, Zvezdana, Backović, A., Stojanović, D., Antić-Stanković, Jelena, and Kovačević, Nada

Subjects
chemical and pharmacologic phenomena
Abstract

The effect of the methanolic extract of the underground parts of Epimedium alpinum L. (MEEA) on the immune response to Keyhole Limpet Hemocyanine (KLH) or alloantigens in vivo was studied in AO rats. Immunization of experimental animals with KLH or allogeneic lymphocytes together with MEEA was followed by an increase in cellularity of draining lymph nodes (LN) and enhanced proliferation of LN lymphocytes after their restimulation with specific antigens in vitro, compared to control rats immunized without MEEA. These effects correlated with an increase in relative values of B, MHC class II+, CD25(+) and CD71(+) cells, whereas percentages of T cells and both subsets of T cells (CD4(+) and CD8(+)) were not significantly altered. As a consequence of higher LN cellularity, total numbers of all cell subsets in the MEEA-treated group of rats were significantly increased, compared to the corresponding control. The addition of MEEA together with KLH in vitro to LN lymphocytes of rats immunized with KLH or KLH and MEEA in vivo was manifested by significant increase (0.1 mu g/ml of MEEA) and decrease (50 mu g/ml and 100 mu g/ml of MEEA) of cell proliferation, respectively. However, when LN lymphocytes from rats, immunized in vivo with KLH and MEEA, were stimulated in vitro with MEEA together with an anti-alpha beta T cell receptor monoclonal antibody (R73), their proliferation was siginificantly inhibited. Taken together, obtained results suggest that MEEA possesses immunostimulatory activity in vivo, but some components from the extract exert immunosuppressive effects in vitro on previously in vivo activated T cells.

Published
2007

54. Use of dietary supplements for children

Author

Stanković, Ivan and Antić-Stanković, Jelena

Subjects
dietary supplements, dijetetski suplementi, infants, vitamins and minerals, mala deca, small children, odojčad, vitamini i mineralne materije
Abstract

Dietary supplements are foodstuffs the purpose of which is to supplement the normal diet and which are concentrated sources of nutrients or other substances with a nutritional or physiological effect, marketed in dose forms (capsules, tablets, drops of liquid, etc) designed to be taken in measured small unit quantities. This food category is well regulated in USA, while in EU harmonization of the laws on food supplements of member states is not finished yet. In our regulations there is no category of dietary supplements and they are classified according to the quantities of nutrients other as dietetic foods or as drugs. Dietary supplements for children are specially prepared, concerning both specific composition and adequate pharmaceutical formulation. Information and education of parents about constituents of these products, as well as of importance of supplementation of particular nutrients is very important that they can, alone or with the help of pharmacist, choose most adequate dietary supplements that can fulfill specific nutritional requirements of their child. Dijetetski suplementi su namirnice koje dopunjuju normalnu ishranu i predstavljaju koncentrovane izvore nutrijenata (vitamina, minerala i drugih supstanci sa hranljivim ili fiziološkim efektom), a u prometu su u doziranim farmaceutskim oblicima dizajnirane da se uzimaju u odmerenim pojedinačnim količinama (kapsule, tablete, kapi i si). Ova kategorija namirnica je detaljno regulisana u SAD 1994. godine, a u EU harmonizacija propisa zemalja članica o dijetetskim suplementima još nije završena. U našoj regulativi ne postoji kategorija dijetetskih suplemenata. U zavisnosti od sadržaja vitamina, minerala ili drugih nutrimenata svrstavaju se u dijetetske namirnice, pomoćna lekovita sredstva ili terapeutska sredstva. Dijetetski suplementi za odojčad i decu su posebno pripremljeni u pogledu specifičnog sastava hranljivih sastojaka i u pogodnom farmaceutskom obliku prilagođenom uzrastu, da bi deca mogla lako da ih konzumiraju. Potrebno je da roditelji budu dovoljno edukovani i pravimo informisani o sastojcima preparata i značaju suplementacije pojedinih nutrimenata da bi sami ili uz pomoć farmaceuta u apoteci mogli da odaberu dijetetske suplemente koji će najadekvatnije da zadovolji specifične potrebe njihovog deteta.

Published
2005

55. Antimicrobial activity of essential oil from root of Carlina acaulis subsp. caulescens on clinical isolates of bacteria

Author

Đorđević, Sofija, Milenković, Marina, Petrović, Silvana, Antić-Stanković, Jelena, and Žižić, Slavica

Subjects
antimicrobial activity, clinical isolates of bacteria, koren, etarsko ulje, Carlina acaulis subsp. caulescens, antimikrobna aktivnost, klinički izolati bakterija, root, essential oil
Abstract

Intrahospital infections are great clinico-therapeutical problem because they are caused by strains of bacteria which are multiresistant. For the purpose of finding new natural raw materials with antimicrobial activity, in this study we tested antibacterial activity of essential oil from Carlina acaulis subsp. caulescens root on clinical isolates of bacteria which are the most common etiological agents of intrahospital infections. Investigation of antibacterial activity of 4% essential oil solution in absolute ethanol was performed by agar dilution technique and broth microdilution technique on different strains of bacteria: Streptococcus pyogenes, Escherichia colt, Klebsiella pneumoniue. Pseudomonas aeruginosa, Slaphylococcus aurews and Acinetobacter spp., isolated from wound swabs and urine of hospitalised patients. Tested solution of essential oil showed high antibacterial activity against Streptococcus pyogenes, medium against Acinetobacler spp., Staphylococcus aureus and Pseudomonas aeruginosa, and moderate against Escherichia coli and Klebsiella pneumoniae. Intrahospitalne infekcije predstavljaju veliki kliničko-terapijski problem, jer su izazvane sojevima bakterija koji pokazuju izrazitu rezistenciju na veći broj antibiotika sa različitim mehanizmima delovanja (multirezistentni sojevi). U cilju iznalaženja potencijalno novih prirodnih sirovina sa antimikrobnim dejstvom, u radu je ispitivano antibakterijsko delovanje etarskog ulja izolovanog iz korena vilinog sita, Carlina acaulis subsp. caulescens, na kliničke izolate bakterija koje poslednjih godina često dovode do intrahospitalnih infekcija. Ispitivanje antibakterijskog delovanja 4% rastvora etarskog ulja u apsolutnom etanolu izvršeno je agar-difuzionom i bujon-dilucionom metodom na različite sojeve bakterija: Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus i Acinetobacter spp., koji su izolovani iz briseva rana i urina hospitalizovanih bolesnika. Ispitivani rastvor etarskog ulja ispoljio je visoku antibakterijsku aktivnost prema Streptococcus pyogenes, znatnu na Acinetohacter spp., Staphvlococcus aureus i Pseudomonas aeruginosa, a umerenu na Escherichia coli i Klebsiella pneumoniae.

Published
2005

56. Metformin Effects on Malignant Cells and Healthy PBMC; The Influence of Metformin on the Phenotype of Breast Cancer Cells

Author

Damjanović, Ana, primary, Matić, Ivana Z., additional, Ðorđić, Marija, additional, Ðurović, Marina Nikolić, additional, Nikolić, Srđan, additional, Roki, Ksenija, additional, Milovanović, Zorka, additional, Antić-Stanković, Jelena, additional, Džodić, Radan, additional, Damjanović, Svetozar, additional, Kanjer, Ksenija, additional, Abu Rabi, Zaki, additional, and Juranić, Zorica, additional

Published
2014
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57. Antiproliferative activity of mixed-ligand Cu(II) complexes with pendant octaazamacrocycle in vitro

Author

Tanasković, Slađana, Tanasković, Slađana, Antić-Stanković, Jelena, Antonijević-Nikolić, Mirjana, Tanasković, Slađana, Tanasković, Slađana, Antić-Stanković, Jelena, and Antonijević-Nikolić, Mirjana

Abstract

Four cationic mixed-ligand complexes of Cu (II) with N, N', N'', N''' -tetrakis (2-pyridylmethyl) -1,4,8,11 -tetraazacyclotetradecane (tpmc) and aliphatic dicarboxylic acids: succinic, glutaric , adipic and sebacic were investigated in vitro on the human cervix adenocarcinoma (HeLa), human malignant melanoma (Fem-x), oestrogen-receptor-positive human breast cancer (MCF-7) cells and the human acute monocyte leukemia cell line (THP1), while free ligands, Cu(II) salt and solvent (used as a controls) were inactive on the same conditions. The metabolic activity of the cells was determined by tetrazolium MTS test. All complexes showed cytotoxicity toward the used cell lines, while free ligands, Cu(II) salt and solvent (used as a controls) were inactive on the same conditions. Increasing the number of - CH2- groups in homologous serie of aliphatic dicarboxylate ligands leads to the increasing cytotoxic activity of the complex. The highest cytotoxic effect of azamacrocycle Cu(II) complexes with glutarate, adipate, sebacinate ligand showed on the cell line MCF-7 and the worst on HeLa cells. A significant effect of sebacinate Cu(II)complex to all tested tumor cell lines applied in concentrations of 100 and 200 μM and up to HeLa cells., Četiri katjonska mešovito-ligandna kompleksa Cu(II) sa N,N',N'N''-tetrakis(2- piridilmetil)-1,4,8,11-tetraaza-ciklotetradekanom i alifatičnim dikarboksilatima: ćilibarnom, glutarnom, adipinskom i sebacinskom kiselinom su ispitivani na humanim malignim ćelijskim linijama: cervikalnog adenokarcinoma (HeLa), melanoma (Fem-X), estrogen pozitivnog karcinoma dojke (MCF-7) i akutne monocitne leukemjie (THP1). Uporedo su testirani i sami ligandi, proste soli i rastvarači. Metabolička aktivnost ćelija je određena MTS testom. Svi ispitivani kompleksi su pokazali citotoksični efekat prema testiranim ćelijskim linijama, dok su slobodni ligandi, Cu(II) so i rastvarač (koji su korišćeni kao kontrolni) pod istim uslovima, bili neaktivni. Sa povećanjem broja -CH2- grupa homologog niza alifatičnih dikarboksilato liganada dolazi i do povećane citotoksičnosti kompleksa. Najveći citotoksični efekat su pokazali makrociklični Cu(II) kompleksi sa glutarato, adipato i sebacinato ligandima prema MCF-7, a najslabiji prema HeLa ćelijama. Najveći antiproliferativni efekat pokazuje kompleks sa sebacinato ligandom prema svim testiranim linijama tumorskih ćelija u primenjenim koncentracijama od 100 i 200 μM, a najviše prema HeLa ćelijama.

Published
2013

58. Funkcionalna karakterizacija CmbT transportera odgovornog za višestruke rezistencije na strukturno različite supstrate u soju Lactococcus lactis subsp. cremoris MG1363

Author

Antić-Stanković, Jelena, Golić, Nataša, Kojić, Milan, Jovčić, Branko, Nikolić, Katarina, Filipić, Brankica V., Antić-Stanković, Jelena, Golić, Nataša, Kojić, Milan, Jovčić, Branko, Nikolić, Katarina, and Filipić, Brankica V.

Abstract

Lactococcus lactis pripada grupi bakterija mlečne kiseline (BMK) i ima dugotrajnu primenu u prehrambenoj industriji kao starter kultura, najviše u proizvodnji tvrdih i polutvrdih sireva. Kako L. lactis ima ključnu ulogu u formiranju ukusa i teksture finalnog proizvoda, a doprinosi i produženju trajnosti namirnica, veliki ekonomski i industrijski značaj doveo je do toga da su laktokoke predmet stalnog izučavanja. Iako se generalno smatraju bezbednim mikroorganizmima, mnogi istraživači ukazuju na činjenicu da laktokoke, kao i druge bakterije mlečne kiseline mogu biti rezervoar gena za rezistenciju. U cilju sprečavanja širenja ovakvih gena na druge bakterije intestinalnog trakta ili patogene bakterije prisutne u hrani, od velikog značaja je izučavanje mehanizama rezistencije, posebno kod laktokoka namenjenih za prehrambenu industriju. Analizom genoma L. lactis detektovano je prisustvo 40 potencijalnih gena za MDR (eng. multidrug resistance) transportere, od čega su svega dva ABC transportera, LmrA i LmrCD i jedan MFS transporter, LmrP funkcionalno okarakterisani. Istraživanja prikazana u ovom radu su imala za cilj da se okarakteriše CmbT (eng. Cysteine and Methionine Biosynthesis Transporter) protein, potencijalno novi MDR transporter u soju L. lactis. Gen cmbT identifikovan je po prvi put prilikom izučavanja regulacije metabolizma sumpora u L. lactis. Primenom različitih kompjuterskih programa, pokazano je da cmbT kodira transmembranski integralni efluks protein (veličine 454 aminokiseline) koji pokazuje homologiju sa članovima 2.A.1.3.X supstrat/H+ antiporter- 2 subfamilije. Prvi korak u funkcionalnoj karakterizaciji CmbT proteina bio je kloniranje i ekspresija cmbT gena pomoću precizno regulisanog NICE (eng. NIsin Controlled gene Expression) sistema..., Lactococcus lactis is a lactic acid bacterium (LAB) widely used as a constituent of many industrial and artisanal starter cultures in dairy industry, especially for fermentation of hard and semi hard cheeses. This organism plays a key role in the formation of flavour and texture of cheese and its preservation and because of the great industrial importance it has been the subject of numerous studies. Although they have acquired the „Generaly Regarded As Safe“ (GRAS) status, many investigators have speculated that lactococci as well as other LAB may act as reservoirs of antibiotic resistance genes. The main threat associated with these bacteria is that they can transfer resistance genes to intestinal microorganisms and food-associated pathogenic bacteria. In order to prevent and reduce the spreading of the resistance genes, more studies of multidrug resistance (MDR) transporters in lactococci intended for use in food systems are needed. The genome analysis of L. lactis indicated the presence of at least 40 putative drug transporter genes, but only two ABC transporters, LmrA, and LmrCD, and one MFS transporter, LmrP, have been studied in detail and all three have demonstrated MDR activity experimentally. The aim of this thesis was to investigate and characterize new MDR transporter CmbT (Cysteine and Methionine Biosynthesis Transporter) in L. lactis. The cmbT gene was originally identified from a random mutagenesis study of cysteine and methionine biosynthesis regulation in L. lactis. This gene is predicted to encode an integral membrane efflux protein (454 amino acids) with homology to members of the 2.A.1.3.X drug/H+ antiporter-2 subfamily of the major facilitator superfamily (MFS). In order to follow the transport function of the CmbT protein, the cmbT gene was cloned and over-expressed in L. lactis NZ9000 using the nisin controlled gene expression (NICE) system...

Published
2013

59. Funkcionalna karakterizacija CmbT transportera odgovornog za višestruke rezistencije na strukturno različite supstrate u soju Lactococcus lactis subsp. cremoris MG1363

Author

Filipić, Brankica, Antić-Stanković, Jelena, Golić, Nataša, Kojić, Milan, Jovčić, Branko, Nikolić, Katarina, Filipić, Brankica, Filipić, Brankica, Antić-Stanković, Jelena, Golić, Nataša, Kojić, Milan, Jovčić, Branko, Nikolić, Katarina, and Filipić, Brankica

Abstract

Lactococcus lactis pripada grupi bakterija mlečne kiseline (BMK) i imadugotrajnu primenu u prehrambenoj industriji kao starter kultura, najviše u proizvodnjitvrdih i polutvrdih sireva. Kako L. lactis ima ključnu ulogu u formiranju ukusa iteksture finalnog proizvoda, a doprinosi i produženju trajnosti namirnica, velikiekonomski i industrijski značaj doveo je do toga da su laktokoke predmet stalnogizučavanja. Iako se generalno smatraju bezbednim mikroorganizmima, mnogiistraživači ukazuju na činjenicu da laktokoke, kao i druge bakterije mlečne kiselinemogu biti rezervoar gena za rezistenciju. U cilju sprečavanja širenja ovakvih gena nadruge bakterije intestinalnog trakta ili patogene bakterije prisutne u hrani, od velikogznačaja je izučavanje mehanizama rezistencije, posebno kod laktokoka namenjenih zaprehrambenu industriju.Analizom genoma L. lactis detektovano je prisustvo 40 potencijalnih gena zaMDR (eng. multidrug resistance) transportere, od čega su svega dva ABC transportera,LmrA i LmrCD i jedan MFS transporter, LmrP funkcionalno okarakterisani.Istraživanja prikazana u ovom radu su imala za cilj da se okarakteriše CmbT(eng. Cysteine and Methionine Biosynthesis Transporter) protein, potencijalno noviMDR transporter u soju L. lactis.Gen cmbT identifikovan je po prvi put prilikom izučavanja regulacijemetabolizma sumpora u L. lactis. Primenom različitih kompjuterskih programa,pokazano je da cmbT kodira transmembranski integralni efluks protein (veličine 454aminokiseline) koji pokazuje homologiju sa članovima 2.A.1.3.X supstrat/H+ antiporter-2 subfamilije.Prvi korak u funkcionalnoj karakterizaciji CmbT proteina bio je kloniranje iekspresija cmbT gena pomoću precizno regulisanog NICE (eng. NIsin Controlled gene Expression) sistema..., Lactococcus lactis is a lactic acid bacterium (LAB) widely used as a constituentof many industrial and artisanal starter cultures in dairy industry, especially forfermentation of hard and semi hard cheeses. This organism plays a key role in theformation of flavour and texture of cheese and its preservation and because of the greatindustrial importance it has been the subject of numerous studies. Although they haveacquired the „Generaly Regarded As Safe“ (GRAS) status, many investigators havespeculated that lactococci as well as other LAB may act as reservoirs of antibioticresistance genes. The main threat associated with these bacteria is that they can transferresistance genes to intestinal microorganisms and food-associated pathogenic bacteria.In order to prevent and reduce the spreading of the resistance genes, more studies ofmultidrug resistance (MDR) transporters in lactococci intended for use in food systemsare needed.The genome analysis of L. lactis indicated the presence of at least 40 putativedrug transporter genes, but only two ABC transporters, LmrA, and LmrCD, and oneMFS transporter, LmrP, have been studied in detail and all three have demonstratedMDR activity experimentally.The aim of this thesis was to investigate and characterize new MDR transporterCmbT (Cysteine and Methionine Biosynthesis Transporter) in L. lactis.The cmbT gene was originally identified from a random mutagenesis study ofcysteine and methionine biosynthesis regulation in L. lactis. This gene is predicted toencode an integral membrane efflux protein (454 amino acids) with homology tomembers of the 2.A.1.3.X drug/H+ antiporter-2 subfamily of the major facilitatorsuperfamily (MFS).In order to follow the transport function of the CmbT protein, the cmbT genewas cloned and over-expressed in L. lactis NZ9000 using the nisin controlled gene expression (NICE) system...

Published
2013

60. Cinnamic Acid Derivatives Induce Cell Cycle Arrest in Carcinoma Cell Lines

Author

Sova, Matej, Sova, Matej, Žižak, Željko, Antić-Stanković, Jelena, Prijatelj, Matevz, Turk, Samo, Juranić, Zorica, Mlinarić-Rascan, Irena, Gobec, Stanislav, Sova, Matej, Sova, Matej, Žižak, Željko, Antić-Stanković, Jelena, Prijatelj, Matevz, Turk, Samo, Juranić, Zorica, Mlinarić-Rascan, Irena, and Gobec, Stanislav

Abstract

Cinnamic acid derivatives can be found in plant material, and they possess a remarkable variety of biological effects. In the present study, we have investigated the cytotoxic effects of representative cinnamic acid esters and amides. The cytotoxicity was determined by MTT test on human cervix adenocarcinoma (HeLa), myelogenous leukemia (K562), malignant melanoma (Fem-x), and estrogen-receptor-positive breast cancer (MCF-7) cells, versus peripheral blood mononuclear cells (PBMCs) without or with the addition of the plant lectin phytohemaglutinin (PHA). The compounds tested showed significant cytotoxicity (IC(50)s between 42 and 166 mu M) and furthermore selectivity of these cytotoxic effects on the malignant cell lines versus the PBMCs was also seen, especially when electron-withdrawing groups, such as a cyano group (compound 5), were present on the aromatic rings of the alcohol or amine parts of the cinnamic acid derivatives. The additional study on cell cycle phase distribution indicated that novel cinnamic acid derivatives inhibit cell growth by induction of cell death. Thus, cinnamic acids derivatives represent important lead compounds for further development of antineoplastic agents.

Published
2013

61. Uticaj povećane ekspresije CmbT MDR transportera na rast Lactococcus lactis

Author

Filipić, Brankica, Jovčić, Branko, Uzelac, Gordana, Miljković, Marija, Antić-Stanković, Jelena, Topisirović, Ljubiša, Golić, Nataša, Filipić, Brankica, Jovčić, Branko, Uzelac, Gordana, Miljković, Marija, Antić-Stanković, Jelena, Topisirović, Ljubiša, and Golić, Nataša

Abstract

U ovom radu je izučavan uticaj povećane ekspresije cmbT gena, odgovornog za sintezu CmbT MDR transportera, na rast Lactococcus lactis. L. lactis pripada grupi bakterija mlečne kiseline (BMK) i ima veliku primenu u prehrambenoj industriji kao starter kultura. CmbT transporter je nedavno okarakterisan MDR protein soja L. lactis, koji doprinosi rezistenciji na različite toksične agense kao i na neke klinički značajne antibiotike. U ovom radu je cmbT gen višestruko eksprimiran u soju L. lactis NZ9000 dodavanjem nizina kao inducera. Povećana ekspresija cmbT gena je praćena metodom reverzne transkripcije (RT-PCR). Pokazano je da se nakon dodatka subinhibitornih koncentracija nizina u medijum za rast povećava količina sintetisane informacione RNK specifične za cmbT gen. Rast soja L. lactis NZ9000/pCT50, u kome je višestruko eksprimiran cmbT gen i L. lactis NZ9000 kontrolnog soja praćen je u bogatom i hemijski definisanom medijumu u prisustvu samo metionina (0.084 mM) ili kombinacije metionina i cisteina (8.4 mM i 8.2 mM). Praćene su krive rasta oba soja, a nakon izračunavanja odgovarajućih vremena generacije, rezultati su pokazali da L. lactis NZ9000/pCT50, brže raste u odnosu na kontrolni soj. Uočena razlika je najverovatnije posledica aktivnosti CmbT transportera koji doprinosi izbacivanju toksičnih agenasa iz ćelije i na taj način poboljšava adaptivne sposobnosti bakterije koja ga eksprimira i daje joj selektivnu prednost., The influence of the over-expression of CmbT multidrug resistance transporter on the growth rate of Lactococcus lactis NZ9000 was studied. L. lactis is a lactic acid bacteria (LAB) widely used as a starter culture in dairy industry. Recently characterized CmbT MDR transporter in L. lactis confers resistance to a wide variety of toxic compounds as well as to some clinically relevant antibiotics. In this study, the cmbT gene was over-expressed in the strain L. lactis NZ9000 in the presence of nisin inducer. Over-expression of the cmbT gene in L. lactis NZ9000 was followed by RT-PCR. The obtained results showed that the cmbT gene was successfully over-expressed by addition of sub-inhibitory amounts of nisin. Growth curves of L. lactis NZ9000/pCT50 over-expressing the cmbT gene and L. lactis NZ9000 control strain were followed in the rich medium as well as in the chemically defined medium in the presence solely of methionine (0.084 mM) or mix of methionine and cysteine (8.4 mM and 8.2 mM, respectively). Resulting doubling times revealed that L. lactis NZ9000/pCT50 had higher growth rate comparing to the control strain. This could be a consequence of the CmbT efflux activity, which improves the fitness of the host bacterium through the elimination of toxic compounds from the cell.

Published
2013

62. Differentiation and function of human monocyte-derived dendritic cells under the influence of leflunomide

Author

Stojić-Vukanić, Zorica, Stojić-Vukanić, Zorica, Čolić, Miodrag, Backović, A., Antić-Stanković, Jelena, Bufan, Biljana, Dimitrijević, M., Stojić-Vukanić, Zorica, Stojić-Vukanić, Zorica, Čolić, Miodrag, Backović, A., Antić-Stanković, Jelena, Bufan, Biljana, and Dimitrijević, M.

Abstract

Leflunomide is an immunosuppressive drug effective in experimental models of transplantation and autoimmune diseases and in the treatment of active rheumatoid arthritis (RA). Having in mind that it has been shown that some other immunosuppressive drugs (glucocorticoids, mycophenolate mofetil, sirolimus etc.) impair dendritic cell (DC) phenotype and function, we investigated the effect of A77 1726, an active metabolite of leflunomide, on the differentiation and function of human monocyte-derived dendritic cells (MDDC) in vitro. Immature MDDC were generated by cultivating monocytes in medium supplemented with GM-CSF and IL-4. To induce maturation, immature MDDC were cultured for 2 additional days with LPS. A77 1726 (100 μM) was added at the beginning of cultivation. Flow cytometric analysis showed that MDDC differentiated in the presence of A77 1726 exhibited an altered phenotype, with a down-regulated surface expression of CD80, CD86, CD54 and CD40 molecules. Furthermore, the continuous presence of A77 1726 during differentiation and maturation prevented successful maturation, judging by the decreased expression of maturation marker CD83, costimulatory and adhesive molecules on A77 1726-treated mature MDDC. In addition, A77 1726-pretreated MDDC exhibited a poor stimulatory capacity of the allogeneic T cells and a low production of IL-10 and IL-18. These data suggest that leflunomide impairs the differentiation, maturation and function of human MDDC in vitro, which is an additional mechanism of its immunosuppressive effect.

Published
2011

63. Beneficial effects of dimethyl sulfoxide on tungstates hepatoprotecitve activity

Author

Uskoković-Marković, Snežana, Uskoković-Marković, Snežana, Milenković, Marina, Topić, Aleksandra, Kotur-Stevuljević, Jelena, Stefanović, Aleksandra, Antić-Stanković, Jelena, Holclajtner-Antunović, Ivanka, Uskoković-Marković, Snežana, Uskoković-Marković, Snežana, Milenković, Marina, Topić, Aleksandra, Kotur-Stevuljević, Jelena, Stefanović, Aleksandra, Antić-Stanković, Jelena, and Holclajtner-Antunović, Ivanka

Abstract

Tungstates and polyoxotungstates have been known to be bioactive compounds for a long time. Based on our previous work about sodium tungstate (ST) and 12-tungstophosphoric acid (WPA) as hepatoprotective agents, we performed a seven week long experiment in rats, using ST and WPA pretreatments in thioacetamide (TAA) induced acute liver necrosis. The possible influences of dimethyl sulfoxide (DMSO), given orally for 3 consecutive days before inducing hepatic lesions, were also investigated. The effects were evaluated by the activity of serum enzymes, oxidative stress parameters, antioxidative defense markers, and histopathology in Wistar rats. The obtained results suggest that oral pretreatment with tungstates, especially ST, in combination with DMSO, before the TAA inducted liver necrosis, could be useful for the prevention of hepatic injury in rats., Volframati i polioksovolframati su decenijama poznati kao biološki aktivna jedinjenja. Kao nastavak prethodnog istraživanja hepatoprotektivnog efekta natrijum volframata (ST) i 12-volframfosforne kiseline (WPA), izveden je eksperiment na Wistar pacovima, koji su pretretirani sa ST i WPA tokom sedam nedelja a nakon tog perioda im je intraperitonealno ubrizgan tioacetamid (TAA) u cilju indukovanja akutne nekroze jetre. Ispitivan je uticaj dimetil sulfoksida (DMSO), koji je primenjivan per os u toku 3 konsekutativna dana pre indukcije hepatične nekroze. Efekti su evaluirani praćenjem aktivnosti serumskih enzima, parametara oksidativnog stresa, antioksidativnog odbrambenog markera, kao i histopatološkom analizom tkiva jetre. Dobijeni rezultati ukazuju da oralni pretretman pacova sa volframatima, pre svega ST, u kombinaciji sa DMSO, može biti koristan u prevenciji nekroze jetre indukovane tioacetamidom.

Published
2009

64. Chemical Composition and Antimicrobial Activity of the Essential Oil from Chaerophyllum aureum L. (Apiaceae)

Author

Lakušić, Branislava, Lakušić, Branislava, Slavkovska, Violeta, Drobac, Milica, Milenković, Marina, Antić-Stanković, Jelena, Couladis, Maria, Lakušić, Branislava, Lakušić, Branislava, Slavkovska, Violeta, Drobac, Milica, Milenković, Marina, Antić-Stanković, Jelena, and Couladis, Maria

Abstract

The essential oils of the aerial parts and fruits of Chaerophyllum aureum L., collected from two Mountains in Serbia, were analyzed by GC and GUMS. Sabinene (18.5-31.6%), p-cymene (7.9-25.4%) and limonene (1.9-10.9%) were characterized as the main constituents. The oils were tested against six bacterial strains and one strain of yeast, Candida albicans. The highest antimicrobial activity was observed against the Gram-positive bacteria Staphylococcus aureus, S. epidermidis and Micrococcus luteus, while of the Gram-negative strains, Escherichia coli was the most sensitive.

Published
2009

65. Chemical composition and antimicrobial activity of the essential oil from Satureja horvatii Šilić (Lamiaceae)

Author

Lakušić, Branislava, Lakušić, Branislava, Ristić, Mihailo, Slavkovska, Violeta, Antić-Stanković, Jelena, Milenković, Marina, Lakušić, Branislava, Lakušić, Branislava, Ristić, Mihailo, Slavkovska, Violeta, Antić-Stanković, Jelena, and Milenković, Marina

Abstract

The present paper describes the chemical composition and antimicrobial activity of the essential oil of the endemic species Satureja horvatii Šilić, collected in Montenegro. The essential oil was obtained from the aerial parts of the plant by hydrodistillation and analyzed by GC-MS. From the 34 compounds representing 100 % of the oil, the major compound was the phenolic monoterpene thymol (63.37 %). The oil contained smaller amounts of g-terpinene (7.49 %), carvacrol methyl ether (4.92 %), carvacrol (4.67 %), p-cymene (4.52%), a-terpinene (1.81 %), borneol (1.58 %), a-thujene (1.56 %), b-caryophyllene (1.55 %) and b-myrcene (1.44 %). The antimicrobial activity of the essential oil of S. horvatii was evaluated using the agar diffusion and broth microdilution methods. The essential oil exhibited antimicrobial activity to varying degrees against all the tested strains. The maximum activity of S. horvatii oil was observed against Gram-positive bacteria (Micrococcus luteus, Staphylococcus epidermidis, Staphylococcus aureus and Enterococcus faecalis) and against the yeast (Candida albicans). The oil exhibited moderate activity against the Gram-negative bacteria Escherichia coli and Klebsiella pneumoniae and weak activity against Pseudomonas aeruginosa. This study confirms that the essential oil of S. horvatii possesses antimicrobial activities in vitro against medically important pathogens., U radu je dat hemijski sastav i antimikrobna aktivnost etarskog ulja, endemične vrste Satureja horvatii Šilić, sakupljane u Crnoj Gori. Etarsko ulje je destilacijom vodenom parom izolovano iz nadzemnog dela biljke i analizirano metodom GC-MS. 34 komponente čine 100 % ulja, a glavna komponenta je timol (63,37 %). Ulje je sadržalo i manji procenat g-terpinena (7,49 %), karvakrol-metil-etra (4,92 %), karvakrola (4,67 %), p-cimena (4,52 %), a-terpinena (1,81 %), borneola (1,58 %), a-tujena (1,56 %), b-kariofilena (1,55 %) i b-mircena (1,44 %). Antimikrobna aktivnost etarskog ulja S. horvatii je ispitivana korišćenjem agar difuzione i bujon mikrodilucione metode. Etarsko ulje je pokazalo različit stepen anti- mikrobne aktivnosti na testirane organizme. Ulje S. horvatii je ispoljilo maksimalnu aktivnost na gram-pozitivne bakterije Micrococcus luteus, Staphylococcus epidermidis, Staphylococcus aureus i Enterococcus faecalis i na gljivicu Candida albicans. Ulje je pokazalo umerenu aktivnost na gram-negativne bakterije Escherichia coli i Klebsiella pneumoniae i slabu na Pseudomonas aeruginosa. Istraživanjem je utvrđeno da etarsko ulje endemične vrste S. horvatii poseduje antimikrobnu aktivnost u in vitro uslovima na značajne medicinske patogene. .

Published
2008

67. Anti-inflammatory and antimicrobial activity of Sideritis scardica extracts

Author

Tadić, Vanja M., Tadić, Vanja M., Đorđević, S., Arsić, I, Dobrić, Silva, Milenković, Marina, Antić-Stanković, Jelena, Tadić, Vanja M., Tadić, Vanja M., Đorđević, S., Arsić, I, Dobrić, Silva, Milenković, Marina, and Antić-Stanković, Jelena

Published
2007

68. Protective effects of tungstophosphoric acid and sodium tungstate on chemically induced liver necrosis in wistar rats

Author

Uskoković-Marković, Snežana, Uskoković-Marković, Snežana, Milenković, Marina, Topić, Aleksandra, Kotur-Stevuljević, Jelena, Stefanović, Aleksandra, Antić-Stanković, Jelena, Uskoković-Marković, Snežana, Uskoković-Marković, Snežana, Milenković, Marina, Topić, Aleksandra, Kotur-Stevuljević, Jelena, Stefanović, Aleksandra, and Antić-Stanković, Jelena

Abstract

Purpose. Many chemical compounds and infectious agents such as viruses induce liver damage like necrosis or fulminant hepatic failure which is sometimes difficult to manage by medical therapies. The induced liver necrosis by carbon tetrachloride (CCl4) and thioacetamide (TAA) are exemplary models for experimental liver necrosis caused by oxygen free radicals. The aim of this study was to investigate the effects of tungstophosphoric acid (TPA) and sodium tungstate (ST) on liver injury induced by CCl4 or TAA. Methods. Hepatoprotective effects of TPA and ST on acute liver necrosis, chemically induced, were evaluated by the activity of serum enzymes (alkaline phosphatase, alanine transaminase and aspartate transaminase), oxidative stress parameters (activity of xanthine oxidase, concentrations of malondialdehyde and production of superoxide anion), antioxidative defence markers (concentration of reduced glutathione), and histopathology in Wistar rats. Liver necrosis was induced by administering a single intraperitoneal (i.p.) injection of CCl4 (1.0 ml/kg b.wt. of 80% CCl4 in corn oil) or a single i.p. injection of TAA (400 mg/kg b.w. dissolved in normal saline). TPA and ST were administrated to rats orally for 7 weeks (50 mg/kg b.wt.) prior to induction of liver necrosis. Results. Induced liver necrosis caused significant elevation of activity of liver enzymes, parameters of oxidative stress and marked changes in histopathology, like necrosis of hepatocytes, hepatocyte degeneration and infiltration of inflammatory cells. In TPA and ST pretreated rats histopathological changes were almost absent, serum enzymes and oxidative stress parameters were decreased, while at the same time the concentration of reduced gluthathione was increased. Conclusion. The present findings suggest that treatment with TPA and ST for 7 weeks could be useful for the prevention of hepatic injury in rats.

Published
2007

69. Composition and antimicrobial activity of essential oil of Stachys plumosa Griseb.

Author

Petrović, Silvana, Petrović, Silvana, Ristić, Mihailo, Milenković, Marina, Kukić, Jelena, Antić-Stanković, Jelena, Niketić, Marjan, Petrović, Silvana, Petrović, Silvana, Ristić, Mihailo, Milenković, Marina, Kukić, Jelena, Antić-Stanković, Jelena, and Niketić, Marjan

Abstract

The essential oil of Balkan endemic Stachys plumosa Griseb. obtained by steam distillation was analysed by GC and GC-MS. Essential oil yield was 0.15% (v/w) and 45 components were identified (86.9% of the total amount). Dehydroabietane was identified as the most prominent component (61.2%), while other constituents were present in much lower quantity, predominantly diterpenes kaurene and biformene (3.2% and 3.0%, respectively). The antimicrobial activity was tested on six bacterial strains and two fungal strains, using the agar diffusion method. Diameters of growth inhibition zones were measured. The most sensitive microorganisms were, in order: Pseudomonas aeruginosa > Bacillus subtilis > Enterococcus faecalis > Klebsiella pneumoniae > Candida albicans (ATCC 10259) > Candida albicans (ATCC 24433) > Escherichia coli > Staphylococcus aureus. Copyright

Published
2006

70. Differentiation of human dendritic cells from monocytes in vitro using granulocyte-macrophage colony stimulating factor and low concentration of interleukin-4

Author

Čolić, Miodrag, Čolić, Miodrag, Jandrić, Dušan, Stojić-Vukanić, Zorica, Antić-Stanković, Jelena, Popović, Petar, Vasilijić, Saša, Milosavljević, Petar, Balint, Bela, Čolić, Miodrag, Čolić, Miodrag, Jandrić, Dušan, Stojić-Vukanić, Zorica, Antić-Stanković, Jelena, Popović, Petar, Vasilijić, Saša, Milosavljević, Petar, and Balint, Bela

Abstract

Several laboratories have developed culture systems that allow the generation of large numbers of human dendritic cells (DC) from monocytes using granulocyte-macrophage colony stimulating factor (GM-CSF), and interleukin-4 (IL-4). In this work we provided evidence that GM-CSF (100 ng/ml) in combination with a low concentration of IL-4 (5 ng/ml) was efficient in the generation of immature, non-adherent, monocyte-derived DC as the same concentration of GM-CSF, and ten times higher concentration of IL-4 (50 ng/ml). This conclusion was based on the similar phenotype profile of DC such as the expression of CD1a, CD80, CD86, and HLA-DR, down-regulation of CD14, and the absence of CD83, as well as on their similar allostimulatory activity for T cells. A higher number of cells remained adherent in cultures with lower concentrations of IL-4 than in cultures with higher concentrations of the cytokine. However, most of these adherent cells down-regulated CD14 and stimulated the proliferation of alloreactive T cells. In contrast adherent cells cultivated with GM-CSF alone were predominantly macrophages as judged by the expression of CD14 and the inefficiency to stimulate alloreactive T cells. DC generated in the presence of lower concentrations of IL-4 had higher proapoptotic potential for the Jurkat cell line than DC differentiated with higher concentrations of IL-4, suggesting their stronger cytotoxic, anti-tumor effect., U više laboratorija su uspostavljeni sistemi za kultivaciju velikog broja humanih dendritičnih ćelija (DĆ) od monocita korišćenjem faktora stimulacije granulocitno--makrofagnih kolonija (GM-CSF) i interleukina-4 (IL-4). U ovom radu je pokazano da je kombinacija GM-CSF (100 ng/ml) i mala koncentracija IL-4 (5 ng/ml) podjednako efikasna za dobijanje nezrelih, neadherentnih, DĆ monocitnog porekla kao i kombinacija GM-CSF sa deset puta većom koncentracijom IL-4 (50 ng/ml). Ovaj zaključak izveden je na osnovu sličnog fenotipskog profila DĆ (ispoljavanje CD1a, CD80, CD86 i HLA-DR, smanjenje ekspresije CD14 i odsustva CD83), kao i slične alostimulatorne aktivnosti ovih ćelija za limfocite T. U kulturama sa nižim koncentracijama IL-4 prisutan je bio veći broj adherentnih ćelija nego u kulturama sa većim koncentracijama IL-4. Međutim, većina ovih ćelija je smanjivala ekspresiju CD14 i stimulisala proliferaciju aloreaktivnih limfocita T. Nasuprot njima adherentne ćelije, diferentovane samo u prisustvu GM-CSF, koje su ispoljavale CD14 i nisu imale sposobnost stimulacije aloreakativnih limfocita T pokazivale su karakteristike makrofaga. DĆ obrazovane u prisustvu manjih koncentracija IL-4 imale su veći potencijal za indukciju apoptoze Jurkat ćelijske linije, a time i snažniji citotoksični, antitumorski efekat nego DĆ diferentovane u prisustvu većih koncentracija IL-4.

Published
2003

72. Facile and Low‐Cost Electrochemical Synthesis of Zinc Alginate Hydrogel Films for Biomedical Applications.

Author

Rupar, Jelena, Marković, Mihajlo, Božić, Dragana, Antić‐Stanković, Jelena, Mijailović, Nataša R., Gavrilov, Nemanja, Bajuk‐Bogdanović, Danica, Milojević‐Rakić, Maja, and Janošević Ležaić, Aleksandra

Subjects
*CELL metabolism, *ALGINIC acid, *HYDROGELS, *ANTI-infective agents, *ZINC
Abstract

ABSTRACT Electrochemical synthesis and characterization of Zn‐alginate hydrogel films and their antioxidant and antimicrobial activity are evaluated. Swelling properties, zinc concentration and spectroscopic and morphological features were characterized and related to their antimicrobial and antioxidant activity. These results indicate a dependence of swelling on the degree of cross‐linking, which, in turn, can be adjusted by manipulating the synthesis time, initial alginate concentration and/or zinc leaching. Hydrogel films with zinc showed remarkable antibacterial properties, especially against gram‐positive bacteria. The absence of Zn resulted in less inhibition of gram‐positive strains, although it had a positive effect on the inhibition of gram‐negative strains, which was attributed to the degradation of alginate chains, affecting cell metabolism. Nitrogen‐doped samples synthesized in rivanol‐containing solution exhibited globular morphology and higher antioxidant activity. The electrochemical synthesis enables the facile preparation of highly active alginate hydrogels for biomedical applications. [ABSTRACT FROM AUTHOR]

Published
2024
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73. Analysis of diagnostic procedures improvement by introducing liquid biopsy in lung adenocarcinoma

Author

Obradović, Anđela, Antić-Stanković, Jelena, and Damjanović-Veličković, Ana

Subjects
liquid biopsy, EGFR, T790M, non-small cell lung cancer
Abstract

Рак плућа је један од водећих узрока смртности међу свим малигним болестима у Србији. Мутације у EGFR гену су често присутне и ови пацијенти су кандидати за терапију 1. и 2. генерацијом инхибитора тирозин киназе (EGFR-TKIs). Међутим, већина пацијената развија резистенцију и прогредира на терапију. Детектовање мутације T790M битне за развој резистенције представља основу за терапију 3. генерацијом EGFR-TKIs. Lung cancer is one of the leading causes of death among all malignant diseases in Serbia. Mutations in the EGFR gene are common and these patients are candidates for first/second generation of tyrosine kinase inhibitors (EGFR-TKIs). However, most patients develop resistance and progress on the therapy. Detection of T790M mutation, which is essential for resistance development, is the basis for treatment with the third generation of EGFR-TKIs.

Published
2023

74. In vitro investigation of antitumor and antimicrobial activities of extracts of mahonia, Mahonia aquifolium (Pursh) Nutt

Author

Damjanović, Ana B., Antić Stanković, Jelena, Stanojković, Tatjana, and Zdunić, Gordana

Subjects
glycocalycs, glikokaliks, invasiveness, berberine type alkaloids, apoptosis, Mahonia aquifolium, biofilm, alkaloidi tipa berberina, invazivnost, antimicrobial effect, cytotoxicity, citotoksičnost, antimikrobni efekat, apoptoza
Abstract

Na osnovu podataka o upotrebi vrste Mahonia aquifolium u tradicionalnoj medicini definisan je cilj našeg istraživanja, ispitivanje antitumorske i antimikrobne aktivnosti ekstrakata kore mahonije. Ispitivanjem citotoksičnosti vodenog i etanolnog ekstrakta na humanim malignim ćelijskim linijama je dokazano da ekstrakti imaju selektivnu citotoksičnu aktivnost, a najviši intenzitet dejstva su pokazali na HeLa ćelijama adenokarcinoma cerviksa. Fluorescentnom mikroskopijom i analizom faza ćelijskog ciklusa je pokazano da ekstrakti indukuju apoptozu u HeLa ćelijama. Primenom inhibitora kaspaza pokazano je da ekstrakti indukuju apoptozu preko spoljašnjeg puta aktivacije. Ispitivanja na endotelijalnim EA.hy926 ćelijama pokazala su antiangiogenetski i antimigratorni efekat ekstrakata. Primena tretmana doksorubicin/ekstrakt ukazala je na izraženo sinergističko dejstvo ekstrakta sa doksorubicinom na A549 ćelijama karcinoma pluća. Ekstrakti povećavaju zadržavanje leka u ćeliji i pojačavaju efekat doksorubicina na smanjenje migracije A549 ćelija i njihovo grupisanje u kolonije. Antimetastatski potencijal kombinacije doksorubicin/ekstrakt potvrđen je analizom ekspresije gena odgovornih za invazivnost. Oba ekstrakta ispoljavaju antimikrobni efekat, koji je najizraženiji na bakterijskoj vrsti Staphylococcus aureus. Ekstrakti dovode do smanjenja produkcije biofilma i glikokaliksa. Sa antibioticima i antimikoticima ekstrakti su delovali sinergistički. Hemijskom analizom potvrđeno je da su za aktivnost ekstrakata M. aquifolium odgovorni alkaloidi tipa berberina. Na intenzitet citotoksičnosti najviše utiču berberin, palmatin i berbamin. Rezultati su pokazali da M. aquifolium može naći svoje mesto u terapiji malignih ili infektivnih oboljenja, pojedinačno i u kombinaciji sa postojećim lekovima. The goal of our research was investigation of antitumor and antimicrobial activities of Mahonia aquifolium extracts and it was based on its use in traditional medicine. Water and ethanol extract exerted selective cytotoxic activity on examined malignant cell lines, and the best activity was observed against cervical adenocarcinoma, HeLa, cells. Fluorescence microscopy and cell cycle analysis showed that both extracts induce apoptosis in HeLa cells. Experiments with caspase inhibitors showed that extracts induce a caspase-dependent apoptosis through extrinsic pathway. Both extracts inhibit the migration of EA.hy926 cells, and exerted anti-angiogenic effect. The investigation of the doxorubicine/extract treatment showed synergistic effect of extracts with doxorubicine against lung carcinoma A549, cells. Extracts were shown to prolong doxorubicin retention time in A549 cells. A549 cells treated with doxorubicin/extract were shown to have lower migratory and colony formation potentials than the cells treated with doxorubicin alone. Antimetastatic effect of the treatment was confirmed with analysis of expression of genes responsible for malignant cells invasiveness. Extracts exerted antimicrobial effect. The best effect was observed against Staphylococcus aureus. Extracts showed potential to inhibit production of biofilm and glycocalycs. The use of extracts with antibiotics and antimycotics showed synergistic effect. Chemical analysis confirmed that berberine type alkaloids are the most responsible for activities of M. aquifolium. The compounds with the highest cytotoxic activity are: berberine, palmatine, and berbamine. The results of our research suggested that M. aquifolium may be used in therapy of malignant or infective diseases, alone or in combination with other drugs.

Published
2018

75. Functional characterization of the CmbT transporter responsible for multidrug resistance on structurally different substrates of the strain Lactococcus lactis subsp. cremoris MG1363

Author

Filipić, Brankica V., Antić-Stanković, Jelena, Golić, Nataša, Kojić, Milan, Jovčić, Branko, and Nikolić, Katarina

Subjects
Lactococcus lactis, CmbT transporter, metabolizam sumpora, QSAR, multidrug resistance, višestruka rezistencija, krive rasta, sulphur metabolism, growth curves
Abstract

Lactococcus lactis pripada grupi bakterija mlečne kiseline (BMK) i ima dugotrajnu primenu u prehrambenoj industriji kao starter kultura, najviše u proizvodnji tvrdih i polutvrdih sireva. Kako L. lactis ima ključnu ulogu u formiranju ukusa i teksture finalnog proizvoda, a doprinosi i produženju trajnosti namirnica, veliki ekonomski i industrijski značaj doveo je do toga da su laktokoke predmet stalnog izučavanja. Iako se generalno smatraju bezbednim mikroorganizmima, mnogi istraživači ukazuju na činjenicu da laktokoke, kao i druge bakterije mlečne kiseline mogu biti rezervoar gena za rezistenciju. U cilju sprečavanja širenja ovakvih gena na druge bakterije intestinalnog trakta ili patogene bakterije prisutne u hrani, od velikog značaja je izučavanje mehanizama rezistencije, posebno kod laktokoka namenjenih za prehrambenu industriju. Analizom genoma L. lactis detektovano je prisustvo 40 potencijalnih gena za MDR (eng. multidrug resistance) transportere, od čega su svega dva ABC transportera, LmrA i LmrCD i jedan MFS transporter, LmrP funkcionalno okarakterisani. Istraživanja prikazana u ovom radu su imala za cilj da se okarakteriše CmbT (eng. Cysteine and Methionine Biosynthesis Transporter) protein, potencijalno novi MDR transporter u soju L. lactis. Gen cmbT identifikovan je po prvi put prilikom izučavanja regulacije metabolizma sumpora u L. lactis. Primenom različitih kompjuterskih programa, pokazano je da cmbT kodira transmembranski integralni efluks protein (veličine 454 aminokiseline) koji pokazuje homologiju sa članovima 2.A.1.3.X supstrat/H+ antiporter- 2 subfamilije. Prvi korak u funkcionalnoj karakterizaciji CmbT proteina bio je kloniranje i ekspresija cmbT gena pomoću precizno regulisanog NICE (eng. NIsin Controlled gene Expression) sistema... Lactococcus lactis is a lactic acid bacterium (LAB) widely used as a constituent of many industrial and artisanal starter cultures in dairy industry, especially for fermentation of hard and semi hard cheeses. This organism plays a key role in the formation of flavour and texture of cheese and its preservation and because of the great industrial importance it has been the subject of numerous studies. Although they have acquired the „Generaly Regarded As Safe“ (GRAS) status, many investigators have speculated that lactococci as well as other LAB may act as reservoirs of antibiotic resistance genes. The main threat associated with these bacteria is that they can transfer resistance genes to intestinal microorganisms and food-associated pathogenic bacteria. In order to prevent and reduce the spreading of the resistance genes, more studies of multidrug resistance (MDR) transporters in lactococci intended for use in food systems are needed. The genome analysis of L. lactis indicated the presence of at least 40 putative drug transporter genes, but only two ABC transporters, LmrA, and LmrCD, and one MFS transporter, LmrP, have been studied in detail and all three have demonstrated MDR activity experimentally. The aim of this thesis was to investigate and characterize new MDR transporter CmbT (Cysteine and Methionine Biosynthesis Transporter) in L. lactis. The cmbT gene was originally identified from a random mutagenesis study of cysteine and methionine biosynthesis regulation in L. lactis. This gene is predicted to encode an integral membrane efflux protein (454 amino acids) with homology to members of the 2.A.1.3.X drug/H+ antiporter-2 subfamily of the major facilitator superfamily (MFS). In order to follow the transport function of the CmbT protein, the cmbT gene was cloned and over-expressed in L. lactis NZ9000 using the nisin controlled gene expression (NICE) system...

Published
2013

76. Protective effects of tungstophosphoric acid and sodium tungstate on chemically induced liver necrosis in wistar rats.

Author

Uskoković-Marković S, Milenković M, Topić A, Kotur-Stevuljević J, Stefanović A, and Antić-Stanković J

Subjects
Acute Disease, Administration, Oral, Animals, Carbon Tetrachloride, Disease Models, Animal, Female, Glutathione metabolism, Liver drug effects, Liver Function Tests, Necrosis chemically induced, Necrosis drug therapy, Necrosis physiopathology, Oxidative Stress drug effects, Rats, Rats, Wistar, Thioacetamide, Antioxidants pharmacology, Liver pathology, Phosphoric Acids pharmacology, Tungsten Compounds pharmacology
Abstract

Purpose: Many chemical compounds and infectious agents such as viruses induce liver damage like necrosis or fulminant hepatic failure which is sometimes difficult to manage by medical therapies. The induced liver necrosis by carbon tetrachloride (CCl4) and thioacetamide (TAA) are exemplary models for experimental liver necrosis caused by oxygen free radicals. The aim of this study was to investigate the effects of tungstophosphoric acid (TPA) and sodium tungstate (ST) on liver injury induced by CCl4 or TAA., Methods: Hepatoprotective effects of TPA and ST on acute liver necrosis, chemically induced, were evaluated by the activity of serum enzymes (alkaline phosphatase, alanine transaminase and aspartate transaminase), oxidative stress parameters (activity of xanthine oxidase, concentrations of malondialdehyde and production of superoxide anion), antioxidative defence markers (concentration of reduced glutathione), and histopathology in Wistar rats. Liver necrosis was induced by administering a single intraperitoneal (i.p.) injection of CCl4 (1.0 ml/kg b.wt. of 80% CCl4 in corn oil) or a single i.p. injection of TAA (400 mg/kg b.w. dissolved in normal saline). TPA and ST were administrated to rats orally for 7 weeks (50 mg/kg b.wt.) prior to induction of liver necrosis., Results: Induced liver necrosis caused significant elevation of activity of liver enzymes, parameters of oxidative stress and marked changes in histopathology, like necrosis of hepatocytes, hepatocyte degeneration and infiltration of inflammatory cells. In TPA and ST pretreated rats histopathological changes were almost absent, serum enzymes and oxidative stress parameters were decreased, while at the same time the concentration of reduced gluthathione was increased., Conclusion: The present findings suggest that treatment with TPA and ST for 7 weeks could be useful for the prevention of hepatic injury in rats.

Published
2007

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