<p>Predviđena istraživanja u ovoj doktorskoj disertaciji su usmerena u pravcu&nbsp;<br />modifikacije klasičnih metoda i postupaka za transformaciju karboksilne grupe&nbsp;<br />prirodnih i sintetičkih karboksilnih kiselina. Modifikacije su rađene novim,&nbsp;<br />savremenim, ekonomski i ekolo&scaron;ki opravdanim metodama rada u&nbsp;<br />mikrotalasnom reaktoru. Modifikovanim sintetskim postupcima u&nbsp;<br />mikrotalasnom reaktoru urađena je sinteza amida, hidroksamskih&nbsp; derivata,&nbsp;<br />kao i redukcija individualnih naftnih kiselina i&nbsp; sme&scaron;e&nbsp; prirodnih naftnih kiselina&nbsp;<br />&bdquo;Velebit&ldquo; do alkohola. Prirodne naftne kiseline kori&scaron;ćene u ovom radu su prvo&nbsp;<br />izolovane iz gasne frakcije (interval destilacije 168-290 &deg;C) vojvođanske nafte&nbsp;<br />&bdquo;Velebit&ldquo; a potom preči&scaron;ćene i razdvojene na uže frakcije na osnovu različite&nbsp;<br />kiselosti. Nakon toga, izvr&scaron;ena je njihova karakterizacija GC-MS-EI analizom&nbsp;<br />(čime je potvrđeno da dolazi do strukturne diferencijacije kiselina). U radu je&nbsp;<br />takođe ispitana biolo&scaron;ka aktivnost sintetizovanih derivata. Proučavan je uticaj&nbsp;<br />prirodnih naftnih kiselina &bdquo;Velebit&ldquo; i njenih derivata na rast&nbsp; pet sojeva&nbsp;<br />Pseudomonas sp., kao i uticaj odabranih sintetisanih jedinjenja na proliferaciju&nbsp;<br />četiri ćelijske linije humanih tumora pri čemu je kao kontrola služila jedna&nbsp;<br />zdrava humana ćelijska linija.</p> / <p>The investigation of this doctoral dissertation is directed toward the modification of the &nbsp;transformation of the carboxylic group of natural and synthetic carboxylic acids. The dissertation takes into consideration the classical methods and procedures of the reaction and modifies them using microwave reactor. The synthesis of amides, hydroxamic derivatives, as well as the reduction&nbsp; of individual petroleum acids and acid mixtures of natural oil &quot;Velebit&quot; to alcohol were achieved&nbsp; by the modifications made to the synthetic methods in the microwave reactor. The natural oil acids used within this study were first isolated from the gas fraction (distillation interval 168-290 &deg;C) of the Vojvodina&#39;s crude oil &quot;Velebit&quot;, and then purified and separated by the narrow fractions under the different acidity. After that, their characterisation was made by the GC-MS-EI analysis which confirmed that the structural differentiation of&nbsp;&nbsp; acids had been achieved. Also, the biological activity of the synthesized derivatives are analysed. The impact of natural petroleum acids &quot;Velebit&quot; and its derivatives on the growth of five strains of&nbsp; Pseudomonas&nbsp; sp. was studied, as well as the impact of selected synthesized compounds on the proliferation of four human tumor cell lines wherein one healthy human cell lines used as the control.</p>

<p>U savremenoj hirurgiji imperativ je da hirur&scaron;ka procedura bude efikasna, ali i da obezbedi kvalitetan i brz oporavak. Najbitniji segment operativnog lečenja je obezbediti maksimalan učinak kako bi se osobi omogućio brz i potpun povratak aktivnostima dnevnog života. Posebno je pojačano&nbsp;&nbsp; interesovanje za rekonstrukciju prednjeg ukr&scaron;tenog ligamenta kod mlađe i sporsko aktivne populacije. Trendovi u medicini kao i u ortopedskoj hirurgiji idu u pravcu smanjenja postoperativnog krvarenja, bola i skraćenja postoperativnog oporavka. Supstancija sa antifibrinolitičkim delovanjem, kao &scaron;to je traneksamična kiselina, svakako je na&scaron;la svoje mesto u smanjenju postoperativnog krvarenja. Ciljevi istraživanja su se odnosili na utvrđivanje uticaja lokalno aplikovane traneksamične kiseline tokom rekonstrukcije prednjeg ukr&scaron;tenog ligamenta kolena na postoperativno krvarenje, posmatrane laboratorijske parametre, mere obima kolena, učestalosti postoperativnih komplikacija i kvaliteta postoperativnog oporavka između dve grupe ispitanika (ispitivana i kontrolna grupa). Studija je bila eksprimentalnog karaktera i sprovedena je u Kliničkom centru Vojvodine u Novom Sadu uz odobrenje etičke komisije. U istraživanje, metodom slučajnog izbora, bila su uključena 124 ispitanika oba pola raspoređena u dve grupe (ispitivana i kontrolna), a kod kojih je indikovana operativno zbrinjavanje prekida prednjeg ukr&scaron;tenog ligamenta kolena i koji su dali pristanak da budu uključeni u studiju. Svi prikupljeni podaci su beleženi u protokol, koji je za ovo istraživanje posebno dizajniran. Ispitanici su bili podvrgnuti operativnom zahvatu, uz primenu op&scaron;te ili spinalne anestezije, sa postavljenom pneumatskom poveskom na operisanom ekstremitetu. Ispitivanoj grupi bilo je lokalno aplikovano 20 ml traneksamične kiseline, dok je u kontolnoj grupi na isti način aplikovano 20 ml NaCl 0,9 % rastvora. Postoperativni gubici krvi su praćeni i beleženi tokom 24 h od operacije, dok su laboratorijki nalazi uzorkovani preoperativno i sedmog postoperativnog dana. U posmatranom periodu (preoperativno, sedmog postoperativnog dana, treće i &scaron;este postoperativne nedelje) kod ispitanika je praćen obim kolena i pojava komplikacija (hematom, hemartroza). Nakon sprovedenog istraživanje, prikupljeni podaci su dokumentovani i statistički obrađeni. Rezultati istraživanja jasno ukazuju da postoji statistički značajna razlika (t=7.181, p&lt;0.001) u količni postoperativnog krvarenja između grupa. Prosečno postoperativno krvarenje u ispitivanoj grupi je bilo 71.29&plusmn;40.76 ml, u odnosu na kontrolnu grupu gde je postoperativno krvarenje iznosilo 154.35&plusmn;81.45 ml. U kontrolnoj grupi, postoperativno se beleže niže vrednosti hemoglobina (t=9.608, p&lt;0.001) i hematokrita (t=8.325, p&lt;0.001), i vi&scaron;e vrednosti trombocita (t=2.201, p=0.032) nego u ispitivanoj grupi. Podaci o postoperativnom bolu ispitanika govore u prilog statistički značajnoj razlici u jačini bola prve nedelje nakon operacije između ispitivane i kontrolne grupe (t=2.405, p=0.018) i treće nedelje nakon operacije (t=3.700, p&lt;0.001). U ispitivanoj grupi zabeležena je ređa pojava hematoma 6.45% (n=4), dok je u kontrolnoj grupi 19.35% (n=12). Svi pacijenti u uzorku su popunili upitnik o postoperativnom kvalitetu oporavka. Nije zabeležena statistički značajna razlika u kvalitetu postoperativnog oporavka nakon operacije između dve analizirane grupe ispitanika. Dobijeni rezultati o postoperativnom krvarenju, nakon aplikovane traneksamične kiseline, ukazuju na efikasnost leka i pri lokalnoj primeni tokom rekonstrukcije prednjeg ukr&scaron;tenog ligamenta kolena. S obzirom na insuficijentnost podataka, ovo ispitivanje stvara &scaron;iru osnovu za dalja istraživanja.</p> / <p>In modern surgery, we need an effective surgical procedure, which provides quality and rapid recovery. The most important segment of surgical treatment is to provide maximum impact to allow a person to return quickly and fully to the activities of daily living. There has been particular interest in the reconstruction of the anterior cruciate ligament in the younger and sport active population. Trends in medicine, as well as in orthopedic surgery, are heading towards reducing postoperative bleeding, pain, and postoperative recovery. A substance with antifibrinolytic activity, such as tranexamic acid, has certainly found its place in reducing postoperative bleeding. The objectives of the study were to determine the effect of locally applied tranexamic acid during the reconstruction of the anterior cruciate knee ligament on postoperative bleeding, observed laboratory parameters, measures of knee circumference, frequency of postoperative complications, and quality of postoperative recovery between the two groups of subjects (study and control group). The study was prospective, conducted at the Clinical Center of Vojvodina in Novi Sad with the approval of the ethics committee. The study, by random selection method, included 124 subjects of both sexes, divided into two groups (tested and control), which indicated operative management of the anterior cruciate ligament rupture and gave informed consent for inclusion in the study. All data collected were recorded in a protocol, which was specifically designed for this research. Subjects underwent surgery, with general or spinal anesthesia, with pneumatic attachment placed on the extremity undergoing surgery. The test group was given topically 20 ml of tranexamic acid, while the control group was administered 20 ml in the same way. NaCl 0.9% solution. Postoperative blood losses were monitored and recorded within 24 h of surgery, while laboratory findings were sampled preoperatively and on the seventh postoperative day. During the observed period (preoperatively, on the seventh postoperative day, on the third and sixth postoperative weeks), the knee volume and the occurrence of complications (hematoma, hemarthrosis) were monitored in the subjects. Following the survey, the data collected were documented and statistically processed. The study results indicate that there was a statistically significant difference (t = 7.181, p &lt;0.001) in the amount of postoperative bleeding between groups. The mean postoperative bleeding in the study group was 71.29 &plusmn; 40.76 ml, compared to the control group where postoperative bleeding was 154.35 &plusmn; 81.45ml. In the control group, lower hemoglobin values (t = 9.608, p &lt;0.001) and hematocrit (t = 8.325, p &lt;0.001) were observed postoperatively, and higher platelet counts (t = 2.201, p = 0.032) than in the study group. The data on the postoperative pain of the respondents support a statistically significant difference in the severity of pain on the first week after surgery between the study and the control group (t = 2.405, p = 0.018) and the third week after surgery (t = 3.700, p &lt;0.001). In the study group, the incidence of hematoma was less than 6.45% (n = 4), while in the control group it was 19.35% (n = 12). All patients in the sample completed a questionnaire on postoperative quality of recovery. There was no statistically significant difference in the quality of postoperative recovery after surgery between the two analyzed groups of subjects. The results of post-operative bleeding, after administrated tranexamic acid, indicate the efficacy of the drug and at a local application during the reconstruction of the anterior cruciate ligament. Due to the insufficiency of data, this study creates a broad basis for further research.</p>

<p>Uvod: Učestalost akutne renalne insuficijencije, odnosno akutnog bubrežnog o&scaron;tećenja u jedinicama intenzivnog lečenja se kreće od 36 do 66 %. Akutno bubrežno o&scaron;tećenje povi&scaron;ava smrtnost, trajanje hospitalizacije i ukupne tro&scaron;kove lečenja. Ranije prepoznavanje prediktivnih faktora za nastanak akutnog bubrežnog o&scaron;tećenja može da ima značajan uticaj na pravovremeno započinjanje terapijskih mera i smanjivanje mortaliteta kod kritično obolelih. Cilj istraživanja: Utvrditi incidencu akutnog bubrežnog o&scaron;tećenja na Odeljenju reanimacije Urgentnog centra Kliničkog centra Vojvodine tokom 2011.godine, učestalost sepse kao etiolo&scaron;kog faktora i značajne prediktivne faktore za nastanak akutnog bubrežnog o&scaron;tećenja koji se javljaju u toku prvih 24 časa lečenja na odeljenju intenzivnog lečenja. Metodologija: Retrospektivno-prospektivna opservaciona studija uključila je uzorak od 251 ispitanika koji su se lečili na dva odeljenja intenzivnog lečenja u Kliničkom centru Vojvodine tokom 2010, 2011, i prvih 6 meseci 2012.godine. Iz medicinske dokumentacije (istorije bolesti, dnevne terapijske liste i liste vitalnih i laboratorijskih parametara) za svakog ispitanika je verifikovano prisutvo ili odsustvo potencijalnog prediktivnog faktora. Zatim je zabeležena pojava akutnog bubrežnog o&scaron;tećenja prema RIFLE kriterijumima. Statistička analiza je izvr&scaron;ena pomoću statističkog paketa IBM SPSS 20 Statistics. Podaci su predstavljeni tabelarno i grafički, a statistička značajnost određivana je na nivou p&lt; 0,05. Prikupljeni podaci su obrađeni standardnim statističkim testovima. Za izvođenje modela predviđanja primenjena je multivarijatna logistička regresija. Određene su granične tačke na osnovu ROC analize za dobijene značajne prediktore iz multivarijacione logističke regresije i izračunati su pridruženi bodovi koji bi činili skoring sistem za utvrđivanje rizika od nastanka akutnog bubrežnog o&scaron;tećenja. Rezultati: Incidenca akutnog bubrežnog o&scaron;tećenja na Odeljenju reanimacije Urgentnog centra Kliničkog centra Vojvodine u Novom Sadu kod bolesnika koji su hospitalizovani najkraće 48 časova u toku 2011.godine je 32 %. Rezna tačka (cut off value) zapremine provocirane diureze jedan čas nakon intravenskog davanja bolusa furosemida od 0,165 ml/kg telesne mase/čas/po miligramu datog furosemida ima najvi&scaron;u senzitivnost (82,3 %) i specifičnost (67,5 %) u diferenciranju bolesnika koji će razviti ABO. Konačni model predloženog skoring sistema sa ulogom predikcije nastanka ABO nakon 24 časa lečenja bolesnika na odeljenju intenzivnog lečenja sadrži sledeće varijable: starost vi&scaron;u od 53 godine, vrednost APACHE skora vi&scaron;u od 16, prosečnu diurezu prvih 6 časova hospitalizacije nižu od 0,875 ml/kg/h, primenu vazopresora, kalijemiju vi&scaron;u od 4,5 mmol/l i koncentraciju laktata iznad 2 mmol/l. Zaključak: Incidenca akutnog bubrežnog o&scaron;tećenja na Odeljenju reanimacije Urgentnog centra Kliničkog centra Vojvodine je slična literaturnim podacima. Bolesnici koji su stariji, imaju vi&scaron;e vrednosti APACHE II skora, nižu prosečnu zapreminu diureze u toku prvih 6 časova po prijemu, koji primaju vazopresorne medikamente, imaju vi&scaron;u koncentraciju kalijuma i vi&scaron;e koncentracije laktata u toku prvih 24 časa lečenja imaju veću &scaron;ansu da razviju akutno bubrežno o&scaron;tećenje.</p> / <p>Introduction: The incidence of acute renal insufficiency (acute kidney injury) in intensive care unit is between 36 and 66 %. Acute kidney injury is responsible for higher mortality, longer hospitalization and higher costs. Earlier recognition of acute kidney injury predictive factors could have important impact on right timing of therapeutic measures and lower mortality in critically ill patients. Aims: investigate the incidence of acute kidney injury during 2011. in patients who are hospitalized at Department of reanimation of Emergency centre, Clinical centre of Vojvodina, incidence of acute kidney injury caused by sepsis in the same period and detect acute kidney injury occurrence predicitive factors Methodology: This retrospective-prospective observational study investigated 251 critically ill patients-study subjects who were treated at two intensive care departments in Clinical centre of Vojvodina during 2010, 2011 and first six months of 2012. Potential predictive factors were identified out of medical records (patient history, daily therapeutic lists, vital parameters and laboratory values lists); the occurrence of acute kidney injury was noted according to RIFLE criteria. IBM SPSS version 20 was used for statistical analysis, standard statystical test were applied. The results were presented in tables and graphs, statystical significance was set at p value of less than 0,05. Multivariate logistic regression model was used for potential predictive factors. Statystically important factors were identified and their best sensitivity and specificity cut-off values were found using ROC curve analysis.; These cut-off values were used for creating a scoring system that determines the risk for acute kidney injury occurrence. Results: The incidence of acute kidney injury at Department of reanimation, Clinical centre of Vojvodina in patients who were hospitalized at least 48 hours was 32 % during 2011. The cut off value of provoked hourly urine output during first hour after furosemide intravenous bolus of 0.165 ml/kg body weight/h/miligram of administered furosemide has the highest sensitivity (82.3 %) and specifity (67.5 %) in differentiation of patients who would develop acute kidney injury and those who would not. The final suggested model of scoring system with the role of acute kidney injury prediction after 24 hours of treatment contains the next variables: age higher than 53 years, APACHE II score higher than 16, avarage hourly urine output during first 6 hours after ICU admission less than 0,875 ml/kg BW/h, vasopressor medication administration, blood potassium concentration higher than 4,5 mmol/l, lactates higher than 2 mmol/l after 24 hours of treatment. Conclusion: The incidence of acute kidney injury at Department of reanimation of Emergency centre, Clinical centre of Vojvodina is similar to world literature references. Critically ill patients who are more likely to develop acute kidney injury are older, have higher APACHE II score values, lower avarage urine output in the first 6 hours after ICU admission, are administered vasopressor medication, have higher blood potassium and lactate concentration in the first 24 hours of their treatment.</p>

<p>Cilj istraživanja u ovom radu bilo je ispitivanje uticaja<br />različitih vidova ekstrakcije (konvencionalna ekstrakcija<br />organskim rastvaračem i superkritična ekstrakcija ugljendioksidom)<br />na kvalitet oleorizina začinske paprike u pogledu<br />kvalitativnog i kvantitativnog sadržaja bojenih materija,<br />sastava masnih kiselina i antioksidativnih svojstava. Po&scaron;to u<br />Vojvodini postoje značajni kapaciteti za proizvodnju i preradu<br />začinske paprike, smatramo da će rezultati ovih ispitivanja<br />dati uvid u kinetiku različitih tipova ekstrakcije i pružiti<br />informacije o uslovima potrebnim za dobijanje proizvoda<br />vrhunskog kvaliteta.</p> / <p>The aim of the work was to investigate the influence of<br />different extraction methods (conventional extraction using<br />organic solvent and supercritical carbon-dioxide extraction)<br />to qualitative and quantitative pigment content, fatty acid<br />content and antioxidant properties of oleoresins. As there<br />have been significant production and processing capacities of<br />spice pepper in Vojvodina, the results of these investigations<br />will give a closer insight into the kinetics of different types of<br />extraction and conditions for obtaining the high quality<br />product.</p>

<p>&nbsp;&nbsp; Cilj ove doktorske disertacije predstavljao je ispitivanje fitohemijskog sastava i biolo&scaron;ke aktivnosti vodenih i metanolnih ekstrakata svežih i suvih plodova, kao&nbsp; i pekmeza&nbsp; pripremljenog&nbsp; po tradicionalnoj recepturi od plodova&nbsp; četiri (od kojih se jedna javlja u dve forme)&nbsp; samonike&nbsp; vrsta&nbsp; roda&nbsp; <em>Sorbus</em>&nbsp; L.:&nbsp; S.<em> aucuparia</em>, S.<em> domestica</em>, S. <em>torminalis</em>&nbsp; f.&nbsp; t<em>orminalis</em>, S. <em>torminalis</em>&nbsp; f. <em>semitorminalis</em>&nbsp; i&nbsp; S. intermedia Ispitivanje fitohemijskog sastava obuhvatalo je LC-MS/MS analizu&nbsp; 44 odabrana fenolna jedinjenja&nbsp; i&nbsp; hinske kiseline (organska&nbsp; kiselina). Takođe, spektrofotometrijski je&nbsp; određen&nbsp; sadržaj&nbsp; ukupnih fenolnih i flavonoidnih jedinjenja, kao i&nbsp; sadržaj askorbinske kiseline. Evaluacija biolo&scaron;ke aktivnosti obuhvatala je&nbsp; <em>in vitro&nbsp; </em>ispitivanja antioksidantne aktivnosti, kao i ispitivanje uticaja ekstrakata odabranih vrsta&nbsp; roda&nbsp;<em> Sorbus</em>&nbsp; na aktivnost enzima acetilholinesteraze, antimikrobni, kao i antiproliferativni potencijal.</p><p>&nbsp;&nbsp; Sumiranjem dobijenih rezultata može se zaključiti da sveži i suvi plodovi ispitivanih vrsta&nbsp; <em>Sorbus</em>,&nbsp; kao i&nbsp; pekmezi&nbsp; predstavljaju&nbsp; umeren izvor&nbsp; fenolnih jedinjenja.&nbsp; Kao najzastupljenije fenolne kiseline izdvojile su se protokatehinska i&nbsp; ferulna, a među flavonoidima amentoflavon i kvercetin-3<em>-O-</em>glukozid.&nbsp; Pored toga, hinska kiselina je zabeležena u značajnoj količini u svim analiziranim ekstraktima.</p><p>&nbsp;&nbsp;&nbsp; Ekstrakti ispitivanih vrsta pokazali su&nbsp; umeren&nbsp; antioksidantni potencijal koji se ogleda u njihovoj sposobnosti neutralizacije nekoliko radikalskih vrsta, redukcionom potencijalu i sposobnosti inhibicije lipidne peroksidacije.&nbsp; Ispitivanjem uticaja ekstrakata odabranih vrsta&nbsp;<em> Sorbus</em>&nbsp; naaktivnost&nbsp; enzima&nbsp; acetilholinesteraze&nbsp; dokazana&nbsp; je&nbsp; jedino&nbsp; umerena aktivnost&nbsp; ekstrakata vrste&nbsp; <em>S. aucuparia</em>.&nbsp; Takođe, ispitivani ekstrakti&nbsp; vrsta roda&nbsp; <em>Sorbus</em>&nbsp; ispoljili su umerenu&nbsp; antimikrobnu&nbsp; aktivnost u pogledu inhibicije&nbsp; rasta Gram pozitivne bakterije,&nbsp; <em>Staphylococcus aureus</em>, i Gram negativne bakterije,&nbsp;<em> Escherichia coli</em>.&nbsp; Vodeni i metanolni ekstrakti svežih i suvih plodova vrste&nbsp; <em>S. aucuparia</em>&nbsp; pokazali su umeren i inhibitorni potencijal prema rastu tumorskih (HeLa, MCF7, HT-29), ali i netumorskih ćelijskih linija (MRC-5).&nbsp; Rezultati dobijeni u ovoj doktorskoj distertaciji&nbsp; ukazuju na značajan&nbsp; biopotencijal plodova i pekmeza&nbsp; ispitivanih vrsta&nbsp;<em> Sorbus</em>&nbsp; i ukazuju na njihovu primenu u prehrambenoj industriji u vidu funkcionalne hrane.</p> / <p>The aim of presented&nbsp; PhD&nbsp; thesis was investigation of phytochemical composition and biological activity of water and methanol extracts of fresh and air-dried&nbsp; fruits, as&nbsp;&nbsp; well&nbsp; as&nbsp; jam,&nbsp; made according to traditional recipe,&nbsp; of fruits&nbsp; of four&nbsp; (one of them occurs in two forms)&nbsp; wild growing&nbsp; <em>Sorbus</em>&nbsp; L. species:&nbsp; <em>S. aucuparia, S. domestica, S. torminalis&nbsp; f. torminalis, S. torminalis f. semitorminalis</em> and <em>S. intermedia</em>. Examination of phytochemical composition included LC-MS/MS analysis of 44 selected phenolic compounds&nbsp; and&nbsp; quinic acid (organic acid).&nbsp; Also, total phenolic and flavonoid contents, as well as&nbsp; ascorbic acid&nbsp; content,&nbsp; were determined spectrophotometrically. Biological activity evaluation of extracts of<em>&nbsp; Sorbus</em>&nbsp; species included&nbsp;<em> in vitro&nbsp;</em> investigation of antioxidant, anti-acetylcholinesterase, antimicrobial&nbsp; and cytotoxic activity.</p><p>&nbsp;&nbsp; According to obtained results, fresh and air-dried&nbsp; fruits, as well as jam&nbsp; present&nbsp; moderate&nbsp; source of phenolic compounds. Amongs examined phenolic acids protocatechuic&nbsp; and ferulic acids were the most abundant, and amongs investigated flavonoids amentoflavone and quercetin-3-<em>O</em>-glucoside wete present in noticeable amount.&nbsp; Furthermore, high concentration of quinic acid was present in all examined extracts.</p><p>&nbsp;&nbsp; Extracts of all examined species showed&nbsp; moderate&nbsp;&nbsp; antioxidant activity in terms of radical scavenging ability, reduction potential and inhibition of lipid peroxidation.&nbsp; Also, investigation of&nbsp; anti-acetylcholinesterase activity revealed moderate activity only of extracts of <em>S. aucuparia</em>. Furthermore, examinated extracts of<em> Sorbus</em> species showedmoderate antimicrobial activity against Gram&ndash;positive bacteria, <em>Staphylococcus aureus</em>, and Gram-negative bacteria,&nbsp;<em> Escherichia coli</em>.&nbsp; In addition, water&nbsp; and methanol&nbsp; extracts of fresh and air-dried&nbsp; fruits of&nbsp;<em> S.aucuparia</em>&nbsp; showed&nbsp; inhibitory activity toward&nbsp; tumor (HeLa, MCF7, HT-29), and also non-tumor (MRC-5) cell lines. Presented results indicate significant&nbsp; biopotential of examined&nbsp; fruits of&nbsp; <em>Sorbus&nbsp;</em> species&nbsp; and&nbsp; support their use in food industry as functional food.</p>

<p style="text-align: justify;">U ovom radu sintetisani su hidrogelovi na osnovu akrilamida i akrilne kiseline, radikalnom polimerizacijom, primenom konvencionalne i mikrotalasne metode sinteze. Varirani su početni odnosi monomera i udeo umreživača, u cilju ispitivanja uticaja sastava reakcione sme&scaron;e na svojstva dobijenih hidrogelova. Optimizovani su uslovi sinteze u mikrotalasnom polju kao brže, jednostavnije i ekonomičnije metode. U cilju uspostavljanja korelacije između mehanizma sinteze, strukture i svojstava dobijenih hidrogelova, primenom relevantnih metoda karakterizacije, upoređena su apsorpciona, reolo&scaron;ka, toplotna i strukturna svojstva hidrogelova dobijenih dvema metodama.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Ustanovljeno je da se mikrotalasnom metodom sinteze na brži i jednostavniji način uz smanjen utro&scaron;ak vremena i energije dobijaju hidrogelovi konkurentni onima koji se dobijaju konvencionalnim zagrevanjem u vodenom rastvoru. Drugi deo doktorata obuhvata sintezu hidrofilnih polimernih mreža na osnovu natrijum karboksimetilceluloze (NaCMC) i karboksilnih kiselina, od kojih je jedna serija sintetisana prožimanjem linearnim kopolimerima akrilamida i akrilne kiseline u cilju povećanja potencijala primene u floku-lacione svrhe. Rezultati ispitivanja svojstava bubrenja, strukturnih toplotnih i flokulacionih svojstava pokazali su međusobno slaganje. Dobijeni rezultati pokazali su da od primenjenih karboksilnih kiselina, linunska kiselina u udelu od 15% u odnosu na masu NaCMC daje hidrogelove najboljih svojstava. Kombinacijom ove mreže sa kopolimerom akrilamida i akrilne kiseline u masenom odnosu 10/90, stvara se teorijska platforma za dobijanja flokulanta koji bi mogao da pokaže visoku efikasnost u preči&scaron;ćavanju vode u kojoj dominiraju pozitivno naelektrisane čestice, pravilnim izborom parametara flokulacije.</p> / <p>In this paper, hydrogels based on acrylamide and acrylic acid were synthesized using conventional and microwave synthetic methods via free-radical polymerization. The initial monomers ratio and amount of crosslinking agent were varied in order to investigate the effect of the composition of the reaction mixture on the properties of the obtained hydrogels. The conditions of synthesis in the microwave field as faster simpler and more economical method have been optimized. In order to establish a correlation between the mechanism of synthesis, structure and properties of the obtained hydrogels using the relevant methods of characterization, the absorption, rheological, thermal and structural properties of the hydrogels obtained by the two methods were compared. It has been found that the microwave synthesis is a faster and simpler method, which enables reduced consumption of time and energy and produces hydrogels competitive to those ones obtained by conventional heating in aqueous solution. The second part of the thesis includes the synthesis of hydrophilic polymer networks based on sodium carboxymethylcellulose (NaCMC) and carboxylic acids, whereby one series is synthesized by interpenetration of the network using the linear acrylamide and acrylic acid copolymers in order to increase the potential application of hydrogels for flocculation purposes. The results of measurements of swelling, structural, thermal and flocculation properites have shown mutual agreement. The obtained results have shown that among applied carboxylic acids, citric acid in the amount of 15% per mass of NaCMC, has given the hydrogels with the best properties. The Combination of this network with a copolymer of acrylamide and acrylic acid in a mass ratio of 10/90 has created a theoretical platform for the production of flocculant which could show high efficacy in purifying of water dominated by positively charged particles.</p>

<p>Danas, u raznim analitičkim laboratorijama postoji veći broj analitičkih protokola,<br />zasnovanih bilo na izuzetno sofisticiranim ili jednostavnijim tehnikama, koji služe za<br />određivanje različitih ciljnih analita od farmakolo&scaron;kog značaja. Među tim grupama ciljnih analita pripadaju i antibiotici koji predstavljaju veliko otkriće u oblasti medicine i zahvaljujući njima spa&scaron;eno je vi&scaron;e od sedam miliona života, ali pored navedenih koristi, antibiotici mogu da izazovu&nbsp; veliki broj neželjenih efekata i žučne kiseline zajedno sa svojim derivatima, koji su fiziolo&scaron;ki deterdženti, mogu biti citotoksične za organizam ako se njihova koncentracija ne kontroli&scaron;e. U ovoj doktorskoj disertaciji prikazan je razvoj analitičkih metoda pre svega voltametrijskihmetoda u kombinaciji sa jednostavnim i savremenim elektrodama/senzorima za određivanje&nbsp; odabranih analita kao &scaron;to je antraciklični antibiotik doksorubicin (DOX), makrolidni antibiotici<br />eritromicin-etilsukcinata (EES), azitromicina (AZI), klaritromicina (CLA) i roksitromicina&nbsp; (ROX) i 3-dehidro-deoksiholne kiseline.</p><p>Voltametrijska karakterizacija i određivanje gore navedenih antibiotika primenom obnovljive srebro-amalgam film elektrode (Hg(Ag)FE)rađena je direktnom katodnom&nbsp; voltametrijom sa pravougaonim talasima (SWV) i visoko osetljivom adsorptivnom voltametrijom sa pravougaonim talasima (SW-AdSV) u Briton-Robinson puferu, kao pomoćnom elektrolitu, obuhvatajući &scaron;irok opseg pH vrednosti. Odgovor DOX-a primenom&nbsp; Hg(Ag)FE&nbsp;praćen je u intervalu potencijala od -0,20 do -0,80 V.&nbsp; Za analizu tragova, optimizacija metode ukazuje da su optimalni parametri za analitički pik na potencijalu (Ep ) -0,57 V u odnosu na zasićenu kalomelovu elektrodu (ZKE): pH 6,0, potencijal&nbsp; akumulacije -0,20 V i vreme&nbsp; akumulacije 140 s. U model rastvoru, DOX je određivan u koncentracionom opsegu 4,99-59,64&nbsp; ng mL^-1. Razvijena SW-AdSV metoda je primenjena za određivanje DOX-a u obogaćenom uzorku humanog urina. Niža koncentracija DOX-a 9,89ng mL^-1&nbsp;u voltametrijskoj&nbsp; ćeliji je određivana sa relativnom standardnom devijacijom (RSD) manjom od 6,0%. &Scaron;to se ispitivanih makrolida tiče oni su pokazali redukcione signale u dalekoj negativnoj oblasti potencijala. Ispitivanja direktnom katodnom SWV rađena su u opsegu potencijala od -0,75 V do -2,00 V u odnosu na ZKE, pri čemu su dobijena jedan ili dva redukciona pika u opsegu potencijala od -1,5 V do -1,9 V. Oblik i intenzitet signala zavisi od primenjene pH vrednosti u &scaron;irokoj pH oblasti. Za analitičke svrhe, radi razvoja direktne katodne SWV i adsorptivne inverzne/striping SWV metode, pogodnim su se pokazale neutralna i slabo alkalna sredina tj. pH 7,0 sa&nbsp; E_p na -1,67 V u odnosu na ZKE za ROX i EES i pH 7,2 sa E_p na -1,85 V u odnosu na ZKE za AZI i pH 7,4 sa E_p na -1,64 V u odnosu na ZKE za CLA. Na osnovu snimljenih cikličnih voltamograma na&nbsp; optimalnim pH vrednostima, može se predložiti adsorptivno-kontrolisan kinetički proces na elektrodi u slučaju sva&nbsp; četiri ispitivana jedinjenja. Takođe,&nbsp; ¹H NMR merenja uz potiskivanje&nbsp; signala vode u pH oblasti između pH 6,0 i 10,5 ukazuju na to da su makrolidni molekuli pri optimalnim analitičkim uslovima predominantno u protonovanoj formi preko tercijerne amino grupe &scaron;to potpomaže, u sva&nbsp; četiri slučaja, njihovu adsorpciju na odgovarajuće polarizovanoj Hg(Ag)FE. Optimizovane direktne katodne SWV metode&nbsp; pokazuju dobru linearnost u koncentracionom opsegu 4,81-23,3&nbsp; &micro;g mL^-1 , 4,53-29,8&nbsp; &micro;g mL^-1 , 1,96-28,6&nbsp; &micro;g mL^-1 i 1,48-25,9 &micro;g mL^-1 za AZI, EES, CLA odnosno ROX. Razvijene SW-AdSV metode rezultiraju u linearnom odgovoru pri nižim koncentracionim intervalima 1,0-2,46 &micro;g mL^-1 ,&nbsp; 0,69-2,44&nbsp; &micro;g mL^-1, 0,05-0,99 &micro;g mL^-1 i 0,10-0,99&nbsp; &micro;g mL^-1 , za AZI, EES, CLA i ROX. RSD za sve razvijene metode nije veća od 1,5% izuzev SWV metode u slučaju AZI-a gde je 4,5%. Direktna katodna SWV metoda&nbsp; je uspe&scaron;no primenjena za određivanje EES-a u farmaceutskom proizvodu Eritromicin^&reg; dok SW-AdSV metoda je primenjena u slučaju određivanja EES-a u obogaćenom uzorku humanog urina i&nbsp;za određivanje ROX-a u farmaceutskom proizvodu Runac^&reg; . U svim pomenutim slučajevima, primenjena je metoda standardnog dodatka. Pouzdanost i tačnost elaboriranih procedura u slučaju određivanja EES-a u model sistemu i&nbsp; farmaceutskom proizvodu Eritromicin^&reg; su potvrđena poređenjem sa rezultatima dobijenim primenom HPLC-DAD metode.</p><p>Nakon preliminarnih studija 3-dehidro-deoksiholne&nbsp; kiseline/3-dehidro-deoksiholata primenom elektrode od staklastog ugljenika (GCE), gde je uočeno da ne dolazi do formiranja redukcionog signala u Briton-Robinson puferu između pH 5,0 i 11,8 primenom direktne katodne SWV, bizmut-film je izdvojen&nbsp; <em>ex situ</em> na povr&scaron;ini iste elektrode od staklastog ugljenika (BiF-GCE) iz uobičajeno kori&scaron;ćenog rastvora za elektrodepoziciju (0,02 mol L^-1 Bi(NO₃)₃, 1,0 mol L^-1 HCl i 0,5 mol L^-1 KBr) i tako pripremljena elektroda je primenjena za karakterizaciju i određivanje pomenutog jedinjenja u alkalnoj sredini. Redukcioni signal ispitivanog analita od analitičkog značaja je uočen jedino primenom BiF-GCE u Briton-Robinson puferusa pH vrednostima između 9,5 i 11,8 u režimu adsorptivne inverzne/stripingvoltametrije sa pravougaonim talasima, dok u slučaju direktnih katodnih SWV eksperimentalnih uslova uočen je slab redukcioni pik sa niskom strujom maksimuma pika. Optimizovani eksperimentalni uslovi za određivanje 3-dehidro-deoksiholata obuhvataju odgovarajuće kondicioniranje elektrode uključujući kondicioniranje&nbsp; <em>ex situ</em> pripremljene BiF-GCE u Briton-Robinson pomoćnom elektrolitu pH 11,8 do stabilizacije struje bazne linije elektrohemijskim cikliranjem potencijala radne elektrode u potencijalskom opsegu između -1,00 i -2,00 V u odnosu na ZKE (blizu 15 puta) i primenu dva ključna parametara adsorptivne voltametrije sa pravougaonim talasima: vreme akumulacije od 30 s i potencijal akumulacije&nbsp; -1,00 V u odnosu na ZKE. Zbog relativne asimetričnosti dobijenih redukcionih signala ispitivanog analita sa&nbsp; E_p na -1,35 V u odnosu na ZKE, &scaron;to je takođe prisutno i u slučaju primene SW-AdSV, određivanje ispitivanog analita je zasnovano na linearnoj zavisnosti između povr&scaron;ine pika redukcionog signala&nbsp; spitivanog analita i njegove odgovarajuće koncentracije i postignuta granica detekcije je 1,43 &micro;g mL^-1 sa dva linearna opsega kalibracione krive od 4,76 &micro;g mL^-1 do 13,0 &micro;g mL^-1 i od 13,0 &micro;g mL^-1 do 23,1 &micro;g mL^-1 za razvoj analitičke metode. RSD metode je 3,22%. Dodatni eksperimenti, elektroliza ispitivanog analita na potencijalu -1,55 V (blizu maksimuma pika ciljnog analita) u odnosu na ZKE su rađeni primenom GCE u obliku ploče (povr&scaron;ina 33,52 cm 2 ) modifikovane sa&nbsp; <em>ex situ&nbsp;</em>pripremljenim bizmut-filmom. Rastvor od interesa uzorkovan je na početku eksperimenta, nakon 2,5 h i nakon 4,5 h tretmana. Ovakvi uzorci su analizirani primenom ¹H NMR merenja uz potiskivanje signala vode u puferskom rastvoru pH 11,8. Može se pretpostaviti da tokom elektrolize 3-dehidro-deoksiholata dolazi do redukcije keto grupe prisutne u strukturi ispitivanog analita.</p><p>Na osnovu literaturnih podataka da neki od ciljnihmakrolidnih antibiotika kao &scaron;to je npr. azitromicin pokazuju oksidativno pona&scaron;anje na elektrodi od ugljenične paste i elektrodi od zlata deteljna karakterizacija i određivanje&nbsp; četiri makrolidna antibiotika rađena je primenom&nbsp; asične&nbsp;elektrode od ugljenične paste (CPE) koja se sastoji samo od grafitnog praha i parafinskog ulja sa optimizovanih direktnih anodnih SWV metoda. U slučaju EES-a i AZI-a diferencijalna pulsna voltametrija (DPV) je testirana za iste svrhe. Ključni&nbsp; parametar u slučaju razvoja analitičkih voltametrijskih metoda je odabir pH vrednosti pomoćnog elektrolita gde je oblik/simetričnost i intenzitet oskidacionog pika glavni kriterijum prilikom odabira. Kao odgovarajuće pH vrednosti za voltametrijsko određivanje EES-a primenom SWV metode odabrana je pH 8,0 sa E_p na 0,83<br />V u odnosu na ZKE, dok u slučaju DPV metode pH 12,0 sa&nbsp; E_p na 0,55 V u odnosu na ZKE je bila najpogodnija za analitičke svrhe. Za određivanje AZI-a, u slučaju obe SWV i DPV metode pH 7,0 se pokazala najpogodnijom sa E_p analitičkog signala na 0,85 V odnosno 0,80 V u odnosu na ZKE, dok u slučaju CLA i ROX koji su ispitivani samo primenom SWV metode za analitičke svrhe pH 12,0 je bila najpogodnija sredina sa E_p analitičkog signala na 0,65 V odnosno na 0,63 V&nbsp;u odnosu na ZKE. Postignute granice detkcije primenom nemodifikovane CPE i direktne anodne SWV su uglavnom u submikrogramskom koncentracionom opsegu 0,17 &micro;g mL^-1 , 0,32&nbsp; &micro;g mL^-1 i 0,30&nbsp; &micro;g mL^-1, u slučaju EES-a, AZI-a i ROX-a i u niskom mikrogramskom koncentracionom opsegu 1,43&nbsp; &micro;g mL^-1 za CLA. Razvijena SWV metoda sa jednostavnom CPE pokazala se pogodnom za određivanje ROX-a u komercijalnom proizvodu Runac^&reg; tableti. U slučaju optimizovanih DPV metoda postignute granice detekcije za EES i AZI su u niskom mikrogramskom&nbsp; koncentracionom opsegu 1,03&nbsp; &micro;g mL^-1 odnosno 1,53&nbsp; &micro;g&nbsp; mL^-1 . U želji da se&nbsp;postigne niža granica detekcije za AZI, DPV metoda&nbsp; je testirana u kombinaciji sa&nbsp; CPE radnom elektrodom povr&scaron;inski modifikovanom sa zlatnim nanočesticama&nbsp; prečnika 10 nm (Au-CPE) i&nbsp; postignuta granica detekcije je 0,95&nbsp; &micro;g mL^-1 sa&nbsp; E_p analitičkog signala na 0,80 V u odnosu na&nbsp; ZKE. RSD metode u slučaju Au-CPE je 3,5%, dok je u slučaju nemodifikovane CPE 6,0%.&nbsp; Linearnost analitičke metode zasnovane na primeni Au-CPE je dva puta &scaron;ira nego u slučaju&nbsp; primene nemodifikovane CPE.</p><p>Na osnovu dobijenih rezultata može se zaključiti da&nbsp; odgovarajuće kombinacije&nbsp; optimizovanih voltametrijskih tehnika sa ekolo&scaron;ki prihvatljivim i lako primenljivim radnim&nbsp; elektrodama, kao &scaron;to su Hg(Ag)FE, BiF-GCE i CPE zajedno sa Au-CPE, rezultuju razvojem&nbsp; pouzdanih analitičkih metoda, kako u oksidacionim tako i u redukcionim proučavanjima, koje&nbsp; često omogućuju&nbsp; određivanje tragova analita od farmakolo&scaron;kog značaja u jednostavnim, a u&nbsp;nekim slučajevima i u složenim sistemima.&nbsp;</p> / <p>Nowadays in different analytical laboratories there is the increasing number of analytical protocols, either based on highly sophisticated or simpler measurements techniques, which serving for determination of different target analytes of pharmacological importance. Among such target groups of the analyte belongs the antibiotics which present a great discovery in the field of medicine and thanks to them were saved more than seven million people but beside to the mentioned great benefits, antibiotics can cause a large number of side effects and bile acids together with their derivatives which are physiological detergents but if their concentration is not<br />controlled they can be cytotoxic to the body. In the present doctoral dissertation the development of analytical methods, primarily analytical voltammetric methods in combination with simple and contemporary electrodes/sensors, for the determination of selected analytes as antracycline antibiotic doxorubicin (DOX), macrolide antibiotics erythromycin ethylsuccinate (EES), azithromycin (AZI), clarithromycin (CLA) and roxithromycin (ROX) and 3-dehydrodeoxycholic acid were performed.</p><p>Voltammetric characterization and determination of the above mentioned antibiotics using a renewable silver-amalgam film electrode (Hg(Ag)FE) was performed by direct cathodic square-wave voltammetry (SWV) and by highly sensitive adsorptive square-wave voltammetry (SW-AdSV) in aqueous Britton-Robinson buffer solutions as supporting electrolyte covering the wider pH range. The Hg(Ag)FE response of DOX was monitored in the potential range between -0.20 and -0.80 V. For the trace level analysis the method optimization showed that the optimal conditions for the analytical peak with peak potential (E_p) at -0.57 V vs. SCE were: the pH 6.0, the accumulation potential -0.20 V, and the accumulation time 140 s. In the model solutions, DOX was determined in the concentration range of 4.99-59.64 ng mL^-1. The developed SWAdSV method was applied for the determination of DOX in spiked human urine sample. The lowest concentration of DOX of 9.89 ng mL^-1 in voltammetric vessel was determined with the relative standard deviation (RSD) less than 6%. As for the investigated macrolides, they showed reduction signals in fairly negative potential range. During direct cathodic SWV investigations conducted over the potential range from -0.75 V to -2.00 V vs. SCE, either one or two reduction peaks were obtained in the&nbsp; potential range from -1.5 to -1.9 V. For analytical purposes concerning the development of direct cathodic SWV and adsorptive stripping SWV methods the neutral&nbsp; and slightly alkaline media were suitable as pH 7.0 with E_p at -1.67 V vs.&nbsp; SCE for ROX and EES and pH 7.2 and pH 7.4 with E_p at -1.85 V and -1.64 V vs. SCE for AZI and CLA, respectively. Based on the cyclic voltammograms recorded at these pH values, adsorptioncontrolled electrode kinetics process can be proposed for all four investigated compounds. The water suppressed ¹H NMR measurements in the pH range between 6.0 and 10.5 indicated that the macrolide molecules at the optimal analytical conditions are predominantly in protonated form via their tertiary amino groups which supported in all four cases their adsorption on the appropriately polarized Hg(Ag)FE electrode. The optimized direct cathodic SWV methods showed good linearity in concentration ranges 4.81-23.3 &mu;g mL^-1, 4.53-29.8 &mu;g mL^-1, 1.96-28.6&nbsp; &mu;g mL^-1, and 1.48-25.9 &mu;g mL^-1 for AZI, EES, CLA and ROX, respectively. The SW-AdSV methods resulted in the linear responses at lower concentration ranges as 1.0-2.46 &mu;g mL^-1, 0.69- 2.44 &mu;g mL^-1, 0.05-0.99 &mu;g mL^-1 and 0.10-0.99 &mu;g mL^-1, for AZI, EES, CLA and ROX, respectively. The RSD for all developed methods was not higher than 1.5% except the SWV method for AZI with 4.7%. The direct cathodic SWV method was successfully applied for the determination of EES in the pharmaceutical preparation Eritromicin^&reg;, while SW-AdSV was tested in the case of the spiked urine sample and for determination of ROX in pharmaceutical preparation Runac^&reg;. In all above cases, the standard addition method was used. The reliability and accuracy of the above procedures in the case of EES determination in model system and pharmaceutical preparation Eritromicin^&reg; were validated by comparing them with those obtained by means of HPLC-DAD measurements.</p><p>After initial study of 3-dehydro-deoxycholic acid/3-dehydro-deoxycholate by glassy carbon electrode, where the absence of any reduction peak was observed in the Britton-Robinson buffer solutions between pH 5.0 and 11.8 by direct cathodic SWV, a bismuth-film was electrodeposited ex situ on the same glassy carbon electrode surface (BiF-GCE) from the usually used plating solution (0.02 mol L^-1 Bi(NO₃)₃, 1.0 mol L^-1 HCl and 0.5 mol L^-1 KBr) and such prepared film-electrode was applied for the characterization and determination of the the target analyte in alkaline media. The reduction signal of analytical importance was observed only by BiF-GCE in Britton-Robinson buffer solutions with pH values between 9.5 and 11.8 in adsorptive stripping square-wave voltammetry working regime, while in the case of the direct cathodic SWV experimental protocol only a very poor reduction peak was obtained. The optimized experimental conditions for the 3-dehydro-deoxycholate determination consist of the optimized electrode conditioning including the electrochemical cycling of the <em>ex situ </em>prepared BiF-GCE potentials in the potential span between -1.0 and -2.0 V vs. SCE (nearly 15 times) in the Britton-Robinson supporting electrolyte pH 11.8 till the stabilization of the baseline current, and the application of two key parameters of the adsorptive square-wave voltammetric protocol: the accumulation time as 30 s and accumulation potential as -1.0 V vs. SCE. Because of the relative asymmetry of the obtained reduction signals of the target analyte with peak E_p at -1.35 V vs. SCE, which is still present in the case of the SW-AdSV, the quantification of the target analyte was based on the linear correlation between peak area of the reduction signal and its appropriate concentrations, and reached limit of detection is 1.43 &mu;g mL^-1 and with two linear ranges of calibration curve from 4,76 &mu;g mL^-1 to 13.0 &mu;g mL^-1 and from 13,0 &mu;g mL^-1 to 23,1 &mu;g mL^-1 for the development of analytical method. The RSD of the method&nbsp; was 3.22%. Additional experiments were performed applying GCE with rectangular form (area 35.32 cm²) modified with ex situ prepared bismuth-film for the electrolysis of the target analyte which was performed at the potential -1.55 V (nearly the peak maxima of the target analyte) vs. SCE. The solution of interest was sampled at the beginning of the experiment, after 2.5 h and after 4.5 h of treatment. Such samples were analysed by simply water suppressing ¹H NMR measurements in the buffered solution at pH 11.8. It can be assumed that during electrolysis of 3-dehydrodeoxycholate the reduction of the keto group present in the structure of the target analyte can be occurred.</p><p>Driven by earlier literature data about the fact that some of the target macrolide antibiotics as e.g. azithromycin showed oxidation behavior at a carbon paste and gold working electrodes detailed characterization and determination of four target macrolide antibiotics were performed on classical carbon paste electrode (CPE) constituted only from graphite powder and paraffin oil with optimized direct anodic SWV methods. In the cases of EES and AZI differential pulse voltammetric (DPV) methods were tested for the same purpose as well. The key parameter in the case of the development of the analytical voltammetric methods is the selection of the pH value of the supporting electrolyte where the shape/simmetry and intensity of the oxidation peak were the criteria. As the appropriate pH value for determination of EES by SWV method the pH 8.0 was selected with E_p at 0.83 V vs. SCE while in the case of the DPV method the pH 12.0 with E_p at 0.55 V vs. SCE was the most suitable for analytical&nbsp; purpose. As for AZI determination, in the case of both SWV and DPV methods the pH 7.0 was the most appropriate supporting electrolyte with the Ep of analytical signal at 0.85 V and 0.80 V vs. SCE, respectively, while in the case of CLA and ROX which were investigated only with SWV method for the analytical purposes the pH 12.0 was the most suitable with E_p at 0.65 V and at 0.63 V vs. SCE. The obtained detection limits applying the bare CPE and the direct anodic SWV are mainly&nbsp; in submicrogram concentration range as 0.17 &mu;g mL^-1; 0.32 &mu;g mL^-1 and 0.30 &mu;g mL^-1 for EES, AZI, and ROX and in the low microgram concentration range as 1.43 &mu;g mL^-1 for the CLA, respectively. The developed method succesfully tested for the determination of ROX in the commercial formulation, Runac^&reg; tablet. In the case of the optimized DPV methods the obtained detection limits for EES and AZI are in the low microgram concentration range 1.03 &mu;g mL^-1 and 1.53 &mu;g mL^-1, respectively. For the improvement of the sensitivity for AZI the DPV method was tested in combination with a&nbsp; CPE working electrode surface modified with gold nanoparticles with diameter of 10 nm (Au-CPE) and reached the limit of detection was 0.95 &mu;g mL^-1 at E_p of 0.80 V vs. SCE. The RSD of the method in the case of the Au-CPE is 3.5% while in the case of the native CPE 6.0%. The linearity of the Au-CPE based analytical method is twice wider then it is case with the bare CPE applying protocol.</p><p>Based on the obtained results it can be conclude that the appropriate combination of the optimized voltammetric pulse techniques and the environmentally friendly and easy to use working electrodes as Hg(Ag)FE, BiF-GCE and CPE together with Au-CPE resulted in the development of reliable analytical method either in the oxidation or reduction studies, often allowing trace level determination of pharmacological importance target analytes in simpler and in some case complexes systems.</p>