Search

Uvod: Pojava SARS-Cov-2 virusa (Severe Acute Respiratory Sindrome Coronavirus 2) uzročnika Covid-19 infekcije (Corona virus disease 2019) dovela je do proglašenja globalne pandemije 11. marta 2020. godine od strane Svetske zdravstvene organizacije (SZO). Koronavirusi su nesegmentisani jednolančani RNK virusi, a jedinstvenost potiče od prisustva spajk proteina i RBD regiona preko kojeg se virus vezuje za ACE2 receptore domaćina. Najveći izazov za lekare predstavljaju kritično oboleli pacijenti sa Covid-19 infekcijom i razvijenom sepsom (čine oko 5% simptomatskih pacijenata). Bez obzira na veliki napredak medicine, sepsa predstavlja vodeći uzrok morbiditeta i mortaliteta u jedinicama intezivne nege (JIN). Od vitalnog značaja je rano prepoznavanje sepse u prvim satima njenog nastanka i preduzimanje adekvatnih terapijskih mera. Biomarkeri i bodovni sistemi: Prema definiciji biomarker je jasno definisana objektivno merljiva karakteristika koja je indikator biološkog i/ili patološkog procesa ili odgovora organizma na izloženost određenoj intervenciji. Biomarkeri i procena kliničkog ishoda mogu da se koriste kao endpoints (precizno definisana varijabla koja se prati kao primarni ishod istraživanja, npr. preživljavanje u određenom vremenskom roku) u kliničkoj medicini. Prognostički biomarkeri se koriste da identifikuju verovatnoću određenog kliničkog ishoda, rekurentnost i progresiju bolesti kod pacijenata sa određenom dijagnozom ili medicinskim stanjem od interesa. Bodovni sistemi za procenu i praćenje sepse u JIN predstavljaju različite setove koji obuhvataju niz parametara direktno povezanih sa funkcijom određenog organskog sistema. Ciljevi i hipoteze: Ciljevi su: Odrediti graničnu vrednost, specifičnost, senzitivnost, pozitivnu prediktivnu vrednost i negativnu prediktivnu vrednost biomarkera sepse (MDW, fibrinogen, D-dimer, LDH, laktat, CRP i prokalcitonin) u proceni 28-dnevnog mortaliteta kod kritično obolelih pacijenata sa Covid-19 infekcijom; Uporediti efikasnost RED, Introduction: The severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) caused a global pandemic health crisis by spreading rapidly across the world. Coronavirus disease (Covid-19) is a highly contagious infectious disease that affects mostly the respiratory system. Receptor-binding domain of spike protein plays most important role in viral attachment with ACE2 host receptors. One of the biggest challenges for medical workers were critically ill patients prone to develop sepsis or septic shock. Time is a crucial factor in treating sepsis in order to enable better overall survival. Biomarkers and scoring systems: According to definition biomarker is objectively measured characteristic which serves as indicator of physiological or patological process or response to specific treatment. Clinical outcome assessment and biomarkers can serve as endpoints in clinical trials (precisely defined variable oriented to outcome such as overall survival) in clinical medicine. Prognostic biomarkers are used to identify likelihood of certain outcome, recurrence and progression of disease. Scoring systems for assessment and monitoring of sepsis in ICU represent specifal set of parameters associated with the function of certain organic systems. Aims and hypotesis: Aims of this study is to determine cut-off, sensitivity, specificity, positive predictive value and negative predictive value of choosed biomarkers (D-dimer, fibrinogen, lactate, LDH, CRP, NLR and MDW) in prediction of 28-day mortality of critically ill patients with Covid-19 infection and sepsis. Second aim is to compare SOFA and REDS scoring system and their effectivness in prediction of 28-day mortality. Third aim is to estimate correlation between MDW and REDS score system. Material and methods: Descriptive, retrospective study was conducted on patients with confirmed Covid-19 infection and sepsis, admitted to the Intensive Care Units of the Institute for Pulmonary Diseases of Vojvodina in Sremska Kamenica in Serbi

Clinical laboratory practice represents an essential part of clinical decision-making, as it influences 60-70% of medical decisions at all levels of health care. Results of biochemical laboratory tests (BLTs) have a key role in establishment of adequate diagnosis as well as in evaluation of treatment progress and outcome. The prevalence of drug-laboratory test interactions (DLTIs) is up to 43% of patients who had laboratory results influenced by drugs. Unrecognized DLTIs may lead to misinterpreted BLTs results, incorrect or delayed diagnosis, extra costs for unnecessary additional tests or inadequate therapy, as all may cause false clinical decisions. The significance of timely and adequate recognition of DLTIs is to prevent common clinical consequences such as incorrectly interpreted test results, delayed or non-treated condition due to erroneous diagnosis or unnecessary extra tests or therapy. Medical professionals should be educated that it is essential to obtain patient data about medications especially for the drugs used in the last 10 days before biological material collection. Our mini-review aims to provide a comprehensive overview of the current state in this important domain of medical biochemistry with detailed analysis of the effect of drugs on BLTs and to give detailed information to medical specialists.

Breast cancer is the most prevalent malignancy in women worldwide. It is estimated that every eight women in the world will be diagnosed with breast cancer at some moment of life. The modern medical approaches have reshaped treatment and diagnostic strategies in management of patients with breast neoplasms, significantly improving quality of life and therapy outcomes. Despite these advances, breast cancer is currently the second leading cause of all cancer-related mortality. Two of the breast cancer subtypes, hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) positive breast cancers, have specific entities on their surface successfully employed in designing targeted therapies. Such treatments enable distinction between malignant and normal tissue, resulting in selective induction of apoptosis in cancer cells. Therefore, development of targeted therapies strongly advanced the prognosis for patients with these breast cancer subtypes. The third type of breast cancers, triplenegative breast cancer (TNBC) represents its most aggressive form, characterized by substantial metastatic potential and higher recurrence rates. In addition, thus far there are no known cell surface receptors that could differentiate the TNBC from normal cells which could be efficiently employed for targeted therapy desing. Thus, this subset is treated with non-specific approaches alone, such as chemotherapy, radiotherapy and surgical procedures. Therefore, TNBC represents a subset of breast cancers with the greatest need for further elucidation of the pathological mechanisms underlying the malignant behavior and investigation of the novel treatment strategies that could exploit this knowledge. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates the expression of genes involved in essential cellular processes including cell growth, survival, proliferation, differentiation, migration and immune response. Constitutive a, Karcinom dojke je na globalnom nivou najučestalije maligno oboljenje kod žena. Prema procenama, svakoj osmoj ženi će u nekom momentu života biti dijagnostikovan karcinom dojke. Savremeni medicinski pristupi su unapredili metode lečenja i dijagnostike u zbrinjavanju pacijenata sa neoplazmom dojke, značajno poboljšavajući kvalitet života i rezultate terapije. Uprkos napretku, karcinom dojke je trenutno drugi vodeći uzrok smrtnosti uzrokovane malignitetom. Dva molekularna podtipa karcinoma dojke, hormon receptor (HR) i humani epidermalni faktor rasta 2 (HER2) pozitivni karcinomi dojke, poseduju specifične strukture na površini maligne ćelije koje su uspešno iskorišćene za dizajniranje ciljanih terapija. Date terapije omogućavaju diferencijaciju između malignog i normalnog tkiva, što rezultira selektivnom indukcijom apoptoze u malignim ćelijama. Stoga je razvoj ciljanih terapija značajno doprineo poboljšanju prognoze za pacijente sa navedenim podtipovima maligniteta dojke. Treći tip karcinoma dojke, trostruko-negativni karcinom dojke (TNBC) predstavlja njegov najagresivniji oblik, koji karakteriše izražen metastatski potencijal i visoka stopa recidiva. Pored toga, trenutno nisu poznati receptori na površini ćelijske membrane koji bi mogli razlikovati TNBC od normalnih ćelija i efikasno bili upotrebljeni za razvoj ciljanih terapija. Stoga se ovaj maligni oblik leči isključivo nespecifičnim pristupima, kao što su hemioterapija, radioterapija i hirurški zahvati. Usled svega navedenog, TNBC predstavlja tip karcinoma dojke sa najvećom potrebom za daljim rasvetljavanjem patoloških mehanizama na kojima zasniva maligno ponašanje kao i istraživanje novih strategija lečenja koje bi mogle iskoristiti dato znanje. Prenosilac signala i aktivator transkripcije 3 (STAT3) je onkogeni transkripcioni faktor koji reguliše ekspresiju gena uključenih u esencijalne ćelijske procese, uključujući ćelijski rast, preživljavanje, proliferaciju, diferencijaciju, migraciju i imunološki odgovor. Kon

Hirurško vađenje impaktiranih donjih umnjaka veoma je česta oralnohirurška intervencija, koja je, u postoperativnom toku, obično praćena neprijatnim tegobama (bol, edem i trizmus), a nekad i potencijalno ozbiljnim komplikacijama (alveolitis i postoperativna infekcija). Stoga se savetuje primena različitih medikamenata i postupaka kojima bi se pojava ovih tegoba i komplikacija predupredila ili ublažila. S tim u vezi, u stručnoj i naučnoj literaturi vodi se rasprava o svsishodnosti profilaktičke primene antibiotika. Interesantno je da se mogu naći brojni radovi u kojima se preporučuje profilaktička primena antibiotika prilikom hirurškog vađenja impaktiranih donjih umnjaka, ali i radovi kojima se obrazlaže neslaganje sa takvim pristupom, potkrepljujući sumnju u odnos koristi spram rizika od uzgrednih efekata antibiotika, tim pre što je rastuća rezistencija mikroorganizama na antibiotike potencijalno ozbiljna pretnja globalnom zdravlju. Po pitanju profilaktičke primene antibiotika u ovoj indikaciji još nije postignut konsenzus, a nijedan od dva suprostavljena stava nije verifikovan ubedljivim naučno potvrđenim dokazima. Cilj. Imajući sve napred rečeno u vidu, osnovni cilj istraživanja bio je da se utvrdi opravdanost profilaktičke primene antibiotika u cilju ublažavanja osnovnih tegoba i komplikacija nakon hirurškog vađenja impaktiranih donjih umnjaka i da se, istovremeno, ispita efikasnost novijih vrsta antibiotika (moksifloksacin i cefiksim) primenjenih na taj način. Pri tom, izvršena su i laboratorijska (mikrobiološka) istraživanja senzitivnosti izolovanih mikroorganizama na antibiotike korišćene u istraživanju, koja bi mogla korisno da verifikuju klinički dobijene rezultate. Imajući to u vidu, na osnovu naučno verifikovanih rezultata, mogu se očekivati dve velike koristi od planiranog istraživanja: (1) potvrda ili negiranje opravdanosti profilaktičke primene antibiotika radi suzbijanja bilo koje od tegoba ili komplikacija posle hirurškog vađenja impaktiranih donjih u, Surgical removal of impacted mandibular wisdom teeth is a frequent intervention, usually accompanied by unpleasant sequelae (pain, oedema and trismus) in the postoperative period, sometimes even with possibly serious complications (dry socket and postoperative infection). It is therefore advisable to use various medications and procedures to prevent or alleviate the occurrence of these sequelae and complications. Accordingly, there is a debate in the literature on the expedience of prophylactic use of antibiotics. It is interesting that numerous articles recommending prophylactic antibiotic use to patients undergoing the impacted mandibular third molar surgerymay be found, as well as those providing arguments for the disagreement with such an approach, considering that its benefits do not outweigh the risks of adverse side effects, especially due to growing resistance of microorganisms towards antibiotics, which is a possible serious threat to global health. Concerning the prophylactic use of antibiotics for this indication, consensus has not yet been reached, and neither of the views has been verified by convincing scientific evidence. Aim. Having the aforementioned dilemma in mind, the main goal of the study was to determine the validity of prophylactic use of antibiotics as to alleviate customary sequelae and possible complications after surgical removal of impacted mandibular third molars and, at the same time, the effectiveness of newer antibiotics (moxifloxacin and cefixime) when used for this purpose. Moreover, microbiological investigations of sensitivity of the isolated microorganisms to antibiotics used in this research were performed, which could verify the clinically obtained results.With this in mind, two major contributions, based on scientifically verified results, could be expected from the research: (1) confirmation or refuting the validity of prophylactic antibiotic use to controlsequelae or complications that could follow the impacted mandibular t

Žučne kiseline deluju kao signalni molekuli u organizmu i uključene su u regulaciju brojnih metaboličkih, inflamatornih i imunomodulatornih procesa. Ova endogena jedinjenja ostvaruju svoje efekte najvećim delom putem nuklearnih receptora. Farnezoid X receptor (FXR) je glavni regulator homeostaze žučnih kiselina, a pokazano je da je značajno uključen i u procese inflamacije i kancerogeneze, prevashodno u jetri i intestinalnom traktu. Aktivacija FXR receptora predstavlja značajnu farmakološku strategiju za terapiju holestatskih bolesti jetre, inflamatorne bolesti creva i karcinoma kolona. Definisana je uloga žučnih kiselina u signalnim putevima koji regulišu ćelijski ciklus i doprinose razvoju ili regresiji maligniteta, ali je malo poznat uticaj ovih jedinjenja na epigenetske mehanizme regulacije ključnih ćelijskih procesa. Imajući u vidu da su efekti žučnih kiselina determinisani njihovom polarnošću, cilj istraživanja je bio da se ispita uticaj sintetski dobijenog keto derivata holne kiseline, 12-monoketoholne kiseline (MKH), u komparaciji sa prirodnim žučnim kiselinama, hidrofobnom henodeoksiholnom kiselinom (HDH) i hidrofilnom ursodeoksiholnom kiselinom (UDH), na ćelijske procese apoptoze, oksidativnog stresa i inflamacije, koji su od značaja za hemoprevenciju i terapiju karcinoma kolona, u in vitro i in vivo sistemima. Cilj istraživanja je takođe obuhvatao i ispitivanje uloge odabranih žučnih kiselina u epigenetskoj regulaciji ovih procesa u ćelijama karcinoma kolona. Na in vivo modelu intrahepatične holestaze kod eksperimentalnih životinja, pokazano je da UDH i MKH ispoljavaju antiapoptotski, antioksidativni i antiinflamatorni efekat u jetri i intestinumu. Utvrđeno je da UDH i MKH sprečavaju mitohondrijalni put aktivacije apoptoze u jetri, dok UDH ispoljava antiapoptotski efekat i u intestinumu eksperimentalnih životinja sa holestazom. Ove dve žučne kiseline su u značajnoj meri modulirale ekspresiju gena uključenih u antioksidativnu zaštitu, kao i aktivnost antio, Bile acids act as signaling molecules in the organism and they are involved in the regulation of numerous metabolic, inflammatory and immunomodulatory processes. These endogenous compounds exert their effects mostly by binding and activation of nuclear receptors. Farnesoid X receptor (FXR) is the main regulator of bile acid homeostasis, and has been shown to be significantly involved in processes of inflammation and carcinogenesis, primarily in the liver and intestinal tract. Activation of FXR receptor represents a significant pharmacological strategy for the treatment of cholestatic liver disease, inflammatory bowel disease, and colon carcinoma. The role of bile acids in signaling pathways regulating the cell cycle and contributing to the development or regression of malignancies is well determined, but the effects of these compounds on epigenetic mechanisms of key cellular processes regulation is yet to be elucidated. Given that the effects of bile acids are mostly determined by their polarity, the aim of our study was to investigate in vitro and in vivo effects of semi-synthetic keto derivative of cholic acid, 12-monoketocholic acid (MKC), in comparison to natural bile acids, hydrophobic chenodeoxycholic acid (CDC) and hydrophilic ursodeoxycholic acid (UDC), on processes of apoptosis, oxidative stress and inflammation, which are significant for both chemoprevention and therapy of colon cancer. Besides, the aim of our study was to examine the role of selected bile acids in the epigenetic regulation of these processes in colon cancer cells. In in vivo model of intrahepatic cholestasis in experimental animals, it has been demonstrated that UDC and MKC exhibit antiapoptotic, antioxidant, and antiinflammatory effects in the liver and intestine. It was shown that UDC and MKC prevent the mitochondrial pathway of apoptosis activation in the liver, while UDC exhibits an antiapoptotic effect in the intestine of experimental animals with cholestasis as well. These two bile

Ugljenične nanocevi (UNC) imaju sve veću primenu u elektronici, kompjuterskoj i optičkoj industriji, kao i u biomedicini. Dok proizvodnja jednoslojnih UNC nanocevi beleži sve veći rast poslednjih godina, rizik koji nosi izlaganje ovom nanomaterijalu ostaje nerazjašnjen. Oskudni i često kontradiktorni podaci o toksičnim efektima jednoslojnih UNC ukazuju na potrebu za daljim ispitivanjima. U našim istraživanjima ispitivane su promene u ćelijskom odgovoru kao i morfološke promene nakon delovanja jednoslojnih ugljeničnih nanocevi na ćelijskoj liniji humanih fetalnih fibroblasta pluća MRC-5 i ćelijskoj liniji humanog adenokarcinoma pluća A549. U ovoj studiji korišćene su jednoslojne ugljenične nanocevi koje su sadržale rezidualne nečistoće poput gvožđa. Citotoksičnost jednoslojnih UNC (engl. single-walled carbon nanotubes – SWCNT) je ispitivana kolorimetrijskim MTT testom. Tokom 24 i 48h niske koncentracije jednoslojnih ugljeničnih nanocevi (<250 μg/mL) pokazale su nisku toksičnost na proliferaciju i vijabilnost u obe ispitivane ćelijske linije. Ipak, pri visokim koncentracijama UNC (250-750 μg/mL) antiproliferativni efekat je bio blizu IC50 vrednostima. Na osnovu rezultata dobijenih MTT testom može se zaključiti da su maligne A549 ćelije osetljivije na delovanje jednoslojnih UNC u odnosu na normalne MRC-5 ćelije. Kombinacija ugljeničnih nanocevi sa prirodnim polifenolima (resveratrolom i proantocijanidolima) nije značajno uticala na citotoksičnost u MRC-5 ćelijama, za razliku od A549 ćelija gde je tretman kombinacijama umanjio toksičnost ugljeničnih nanocevi. Transmisionom elektronskom mikroskopijom ispitivan je efekat jednoslojnih ugljeničnih nanocevi na ćelijsku morfologiju i preživljavanje. Intracelularni agregati ugljeničnih nanocevi primećeni su u obe ćelijske linije, čime je potvrđeno da ugljenične nanocevi ulaze u ćelije. Imajući u vidu da nanomaterijali poput ugljeničnih nanocevi indukuju oksidativni stres i njime posredovanu apoptozu, na protočnom citometru je, Carbon nanotubes are being actively introduced in electronics, computer science, and optics as well as for various biomedical applications. While production of single-walled carbon nanotubes (SWCNT) has escalated in recent years, the knowledge on risk associated with exposure remains unclear. Contradictory data on the toxic effects of single-walled carbon nanotubes highlights the urgent need for further studies. In this study we investigated the alterations in cellular response along with morphological changes induced by single-walled carbon nanotubes in human lung fibroblast cell line MRC-5 and adenocarcinoma human alveolar basal epithelial cells A549. In this study we used SWCNT containing large amounts of residual metallic impurities such is iron, and the iron concentration increased in dose dependent manner in cells exposed to SWCNT. Cytotoxicity was evaluated by MTT assay and SWCNT showed little cytotoxic effect on the proliferation and viability of two cell lines tested at the concentrations used (<250 μg/mL) within 24 and 48h. However exposing both cell lines to high concentrations (250-750 μg/mL) resulted in near IC50 values. Based on MTT test SWCNT were more cytotoxic to A549 cell line. Cytotoxicity of SWCNT in combination with natural polyphenols (resveratrol and proanthocyanidins) did not noticeably affect the cytotoxicity of SWCNT to MRC-5 cells. However introduction of polyphenols did reduce the cytotoxicity of SWCNT to A549 cells. Transmission electron microscopy was used to complement cytotoxicity assays and to investigate the pathological effect of internalized SWCNT on cell morphology and survival. Intracellular bundles of CNTs, possibly aggregated/agglomerated were observed in both cell lines, confirming internalization after 24h exposure. Since nanoparticles like carbon nanotubes are toxic mainly because they cause oxidative stress, often associated with an increased apoptosis we checked for apoptotic and necrotic cells using flow cytometry. Incub

Zahvaljujući amfifilnoj strukturi i mogućnosti građenja konjugata, žučne kiseline - endogeno sintetisani produkti katabolizma holesterola su prepoznate kao potencijalni nosači lekova i promoteri transporta kroz biološke membrane. Otkriće da aktivacijom specifičnih nuklearnih receptora regulišu ekspresiju gena uključenih u plejadu signalnih puteva uključenih u metabolizam, proliferaciju i diferencijaciju ćelija i onkogenezu, proširilo je ulogu žučnih kiselina u odnosu na inicijalno opisanu ulogu intestinalnih emulgatora. Žučne kiseline se danas ne smatraju samo pasivnim nosačima lekova i promoterima transporta kroz biološke membrane već i molekulima sa farmakodinamskom funkcijom, koji regulišu različite aspekte integrativnog ćelijskog metabolizma. Doksorubicin je jedan od najčešće korišćenih antineoplastičkih agenasa i sastavna je komponenta mnogih hemoterapijskih protokola u lečenju solidnih i hematoloških maligniteta. Međutim, hepatotoksični i kardiotoksični efekti značajno ograničavaju upotrebu ovog, inače veoma korisnog antitumorskog agensa. Pojava odložene dozno-zavisne kardiotoksičnosti predstavlja značajan zdravstveni problem onkoloških pacijenata sa uspešno lečenim malignitetom, naročito pacijenata lečenih u pedijatrijskom uzrastu. Budući da je razvoj novih lekova veoma dug i skup proces sa neizvesnim ishodom, poboljšanje farmakodinamskih i farmakokinetskih svojstava već postojećih antitumorskih agenasa sa dokazanom efikasnošću, uz smanjenje toksičnih efekata, predstavlja racionalan istraživački pristup u savremenoj medicini. Osnovni cilj ovog rada je ispitivanje uticaja žučnih kiselina ursodeoksiholne, henodeoksiholne i 12-okso-henodeoksiholne kiseline (12-monoketoholne kiseline) na citotoksičnu aktivnost doksorubicina prema MCF-7 ćelijskoj liniji humanog adenokarcinoma dojke i ispitivanje molekularnih mehanizama odgovornih za farmakodinamske efekte. Takođe su navedene žučne kiseline ispitane kao promoteri transporta koji utiči na prodor i kumulaciju doksoru, Due to the amphiphilic structure and the significant conjugation potential, bile acids - endogenously synthesized products of cholesterol catabolism have been recognized as potential drug carriers and promoters of transport through biological membranes. The discovery that by activating specific nuclear receptors bile acids regulate the expression of genes involved in various signaling pathways including metabolism, cell proliferation and differentiation as well as carcinogenesis, expanded initially ascribed role of intestinal emulsifiers to the various fields. Bile acids are now considered not to act only as passive carriers of drugs and promoters of transport through biological membranes, but also as the molecules with pharmacodynamic activity, regulating various aspects of integrative cellular metabolism. Doxorubicin is one of the most commonly prescribed antineoplastic agents as an integral component of many chemotherapy protocols in the treatment of both solid and hematologic malignancies. However, hepatotoxic and cardiotoxic effects significantly limit the use of this, otherwise, very useful anti-tumor agent. The development of dose-dependent cardiotoxic side effects represents particular health issue in successfully treated oncological patients, especially among survivors of pediatric malignancies. Since the development of new drugs is very long and expensive process with an uncertain outcome, improving the pharmacodynamic and pharmacokinetic properties of the existing agents with proven efficacy, while reducing toxic side effects, represents a rational approach to research in modern medicine. The main objective of this work is to examine the role of bile acids: ursodeoxycholic, chenodeoxycholic and 12-oxo-chenodeoxycholic acid (12-monoketocholic acid) on the cytotoxic activity of doxorubicin in the MCF-7 human breast adenocarcinoma cell line, and to get insight on molecular mechanisms responsible for underlying pharmacodynamic effects. The capacity of bile ac

Kardijalni biomarkeri u predviđanju operativnog rizika kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore Evaluacija rezultata u kardiohirurgiji podrazumeva praćenje ishoda operativnog lečenja u određenom vremenskom periodu. Najčešće je to interval od 30 dana od datuma intervencije. Najčešći kriterijumi za praćenje su stopa mortaliteta i morbiditeta, dužina boravka u jedinici intenzivnog lečenja, ukupna dužina hospitalizacije i troškovi lečenja. Stratifikacija rizika podrazumeva da se bolesnici mogu podeliti u grupe u zavisnosti od broja i važnosti preoperativno utvrđenih faktora rizika, odnosno da se pre operacije može predvideti ishod hirurške intervencije kod svakog od njih pojedinačno. U Evropi je, u periodu između 1995. i 1999. godine, na osnovu multicentrične studije u 8 evropskih zemalja i 128 kardiohirurških centara u kojima je operisano 19.030 odraslih bolesnika, kreiran EvroSKOR - EuroSCORE (European System for Cardiac Operative Risk Evaluation) model za stratifikaciju rizika u kardiohirurgiji. Međutim, neminovne promene i napredak u operativnom lečenju doveli su do toga da je neophodno ažurirati postojeći sistem stratifikacije. Tako je 2012. godine u rutinsku upotrebu uveden novi sistem Euroscore II. Na Klinici za kardiohirurgiju Instituta za kardiovaskularne bolesti Vojvodine (IKVBV), EuroSCORE model uveden je u rutinsku upotrebu od početka 2001. godine. Analizom rezultata, posle dvogodišnje primene, pokazalo se da je model bio precizan, odnosno da nije postojala značajna razlika između očekivanog (3,7%) i stvarnog mortaliteta (3,47%). U poslednjih nekoliko godina, kod bolesnika kojima sledi kardiohirurška intervencija, u smislu razmatranja njihove prediktivne vrednosti, sve više pažnje se poklanja kardijalnim biomarkerima. Najznačajniji biomarkeri u kardiovaskularnoj medicini su: Troponin, Kreatin kinaza MB izoenzim (CKMB), N-terminalni pro B-tip natriuretski peptid (NT-proBNP), C-reaktivni protein (CRP), Laktat dehidrogenaza (LDH), Cardiac surgery operative risk assessment in patients with imapired systolic left ventricular function using cardial biomarkers Evaluation of results in cardiac surgery involves monitoring the outcomes of operative treatment in a given time period. Typically, this interval includes 30 days from the date of operation. The most common criteria used for monitoring are the rate of mortality and morbidity, length of stay in the intensive care unit, the total length of hospitalization and medical costs. Risk stratification means that patients can be divided into groups depending on the number and importance of preoperatively identified risk factors, and that the outcome of surgery for each of the patients can be predicted preoperatively. In Europe, in the period of 1995-1999 on the basis of a multi-center study in 8 European countries and 128 cardiac centers in which 19,030 adult patients were operated on, EuroSCORE (European System for Cardiac Operative Risk Evaluation) model for risk stratification in cardiac surgery was developed. However, the inevitable changes and progress in the surgical treatment rendered the EuroSCORE model obsolete warranting updated system. It was in 2012 when a new system EuroSCORE II was introduced into practice At the Clinic for Cardiac Surgery of the Institute of Cardiovascular Diseases, EuroSCORE model was introduced in routine clinical use since the beginning of 2001. By analyzing the results, two years after application, it was shown that the model was accurate, and that there was no significant difference between the expected (3.7%) and the actual mortality (3.47%) In recent years, in patients who are candidates for cardiac surgery, more attention is paid to cardiac biomarkers in terms of evaluating their predictive power. The most significant biomarkers in cardiovascular medicine are: Troponin, creatine kinase MB isoenzyme (CKMB), N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), Lactate dehydrogenase (LDH

Žučne kiseline (ŽK) su strukturno raznoliki molekuli, koji pored uloge koju ostvaruju putem žuči, deluju i kao signalni molekuli i ostvaruju kako endokrina tako i parakrina dejstva. Činjenica da je do sada u terapijske svrhe primenjivana samo ursodeoksiholna kiselina (UDK), posledica je brojnih ograničenja u mogućnosti primene ostalih prirodnih ŽK, i ističe potrebu za otkrivanjem novih sintetskih ŽK i liganda. Cilj istraživanja bio je ispitivanje sintetske 12-monoketoholne kiseline (MK) i prirodne UDK u modelu holestaze i aloksanom izazvanog dijabetesa. Ispitivanja su vršena na pacovima soja Wistar. Analizirana je telesna masa, glikemija, pokazatelji jetrene funkcije (AST; ALT, γ-GT, ukupni i direktni bilirubin), a iz homogenate jetre određen je intenzitet lipidne peroksidacije i aktivnost antioksidativnih enzima (CAT, GSH-Px, GSH-R, GSH-ST). Isečci tkiva jetre su histološki obrađeni i bojeni hematoksilin-eozin metodom i histohemijskim metodama (retikulin, Mallory, Periodic Acid Schiff- Alcian Blue (PAS/AB)). Imunohistohemijski je ispitana proliferacija hepatocita (Ki-67), markeri apoptoze (p53, Bcl-2, Bcl-X, Bax) i ekspresija nuklearnog farnesoid X receptora (FXR). Rezultati istraživanja pokazuju da ispitivane ŽK pomažu očuvanje telesne mase u holestazi i dijabetesu, i značajno snižavaju glikemiju kod dijabetičnih jedinki. Parametri jetrene funkcije u holestazi i dijabetesu su regulisani primenom MK i UDK. Obe ŽK u značajnoj meri smanjuju intenzitet lipidne peroksidacije i pojačavaju enzimsku antioksidativnu odbranu hepatocita u holestazi i dijabetesu. Ekspresija markera apoptoze nije značajno promenjena izazvanjem modela holestaze i dijabetesa, kao ni primenom ispitivanih ŽK. Nasuprot tome, izazivanje holestaze i dijabetesa značajno smanjuje proliferaciju hepatocita, dok primena MK i UDK poništava ovaj efekat i značajno povećava proliferaciju hepatocita. Hiperglikemija u aloksanskom dijabetesu nije dovela do pojačane ekspresije FXR. Izazivanje holestaze kod zdravi, Bile acids (BAs) are structurally diverse molecules, which have theroles in the digestive system, which are exercised through the bile. Beside those, BAs act as a signaling molecules and achieve endocrine and paracrine effects. In addition to its own metabolism, bile acids modulate the metabolism of lipids and glucose. The fact that so far only ursodeoxycholic acid (UDC) is used for therapeutic purposes, speak clearly about of numerous limitations on the application of other natural BAs, and highlights the need to develop new synthetic Bas and ligands. The aim of this study was to investigate the influence of synthetic 12-monoketocholic acid (MC) and natural bila acid UDC in the model of cholestasis and alloxan-induced diabetes. Tests were performed on male Wistar rats. We analyzed the body mass, glucose, liver function tests (AST, ALT, γ-GT, total and direct bilirubin). Using liver tissue homogenates we determined intensity of lipid peroxidation (by concentration of malondilaldehyde) and the activity of antioxidant enzymes (CAT, GSH-Px, GSH -R, GSH-ST). Liver tissue were histologically processed and stained with hematoxylin-eosin method and histochemical methods (reticulin, Mallory, Periodic Acid Schiff- Alcian Blue (PAS / AB)). Imunohistochemical examination included hepatocyte proliferation (Ki-67), markers of apoptosis (p53, Bcl-2, Bcl-X, Bax), and expression of the nuclear farnesoid X receptor (FXR). Results of the research show that MC prevented decrease in body mass during cholestasis and diabetes, and significantly reduced glycemia in diabetic animals. The liver function tests in cholestasis and diabetes are normalised by MC and UDC aplication. Both BAs significantly reduce lipid peroxidation and enhance enzymatic antioxidant defense of hepatocytes in cholestasis and diabetes. The expression of markers of apoptosis was not significantly changed in models of cholestasis and diabetes, as well as the application of the tested BAs. In contrast, in cholestasis an