Search

U radu je obrađena problematika matematičkog modeliranja ekoloških procesa u jezerima i akumulacijama. Prikazani su principi matematičkog modeliranja najbitnijih fizičkih, hemijskih i bioloških procesa koji utiču na kvalitet vode u jezeru. Izvršena je podela modela kvaliteta vode i prikazan je postupak pripreme ulaznih podataka. Programom WASP4 modeliran je kvalitet vode u akumulaciji Vitman. Ispitivani su efekti smanjenja koncentracije zagađenja u reci Mlavi i njenim pritokama na kvalitet vode u akumulaciji. Mathematical modelling of water quality in lakes and reservoirs is considered. The principles of mathematical modelling of main physical, chemical and biological processes that affect water quality are presented. The classification of water quality models, and process of preparing input data are given. Water quality in reservoir Vitman is simulated by WASP4 modelling program. The effects of reducing pollution concentration in river Mlava and tributaries on water quality in reservoir are examined.

Bolest malih krvnih sudova mozga podrazumeva nekoliko kliničkih sindroma koji proističu iz oštećenja zida ili začepljenja malih krvnih sudova unutar moždanog tkiva. Udružena je sa faktorima rizika kao što su hipertenzija, dislipidemija, dijabetes, gojaznost, ishemijska bolest srca, pušenje i zloupotreba alkohola. Jedan od potencijalnih faktora rizika za nastanak bolesti malih krvnih sudova mozga je metabolički sindrom. Bolest se klinički manifestuje neuroškim simptomima, kognitivnim disfunkcijama i depresijom. Istraživanje je sprovedeno kod pacijenata koji su hospitalizovani na Klinici za neurologiju KC Kragujevcu u periodu od 01.02.2017. do 31.12.2017. godine, kod kojih je neuroradiološki potvrđena bolest malih krvnih sudova (magnetnom rezonancom endokranijuma). Bilo je uključeno 49 odraslih bolesnika sa bolešću malih krvnih sudova mozga (24 sa lakunarnim infarktima i 25 sa ishemijskim, hiperintenzivnim lezijama bele mase). Kontrolnu grupu činilo je 25 neuroloških pacijenata sa urednim nalazom na magnetnoj rezonanci endokranijuma, sličnog pola i starosti. Sa pacijentima je postupano prema lokalnim smernicama i kliničkim putevima koji nisu povezani sa ovom studijom, već predstavljaju deo rutinske nege neuroloških bolesnika u Kliničkom centru Kragujevac. Rezultati prikazani u ovom radu ukazuju da je bolest malih krvnih sudova mozga praćena slabljenjem kognitivne sposobnosti i depresivnim simptomima, pri čemu pacijenti sa lakunarnim infarktima imaju slabiju kogniciju i izraženije depresivne simptome od pacijenata sa hiperintenzivnim lezijama bele moždane mase. Takođe, pacijenti sa bolešću malih krvnih sudova mozga koji imaju i metabolički sindrom su više depresivni i manje kognitivno sposobni od pacijenata sa bolešću malih krvnih sudova mozga, ali bez metaboličkog sindroma. Disease of the small blood vessels of the brain involves several clinical syndromes arising from damage to the wall or obstruction of the small blood vessels inside the brain tissue. It is associated with risk factors such as hypertension, dyslipidemia, diabetes, obesity, ischemic heart disease, smoking and alcohol abuse .One of the potential risk factors for developing cerebral small vessels disease is the metabolic syndrome. The disease is clinically manifested by neurological symptoms, cognitive dysfunctions and depression. The study was conducted in patients hospitalized at the Kragujevac Clinic for Neurology in the period from 01.02.2017. to 31.12.2017, in which neuroradiologically confirmed disease of the small blood vessels (magnetic resonance imaging of the endocranium). There were 49 adult patients with small cerebral blood vessels disease (24 with lacunar infarctions and 25 with ischemic, hyper intense white mass lesions). The control group consisted of 25 neurological patients with neat endocranial magnetic resonance imaging, of similar sex and age. Patients were treated according to local guidelines and clinical pathways not associated with this study, but are part of the routine care of neurological patients at the Clinical Center Kragujevac. The results presented in this paper indicate that cerebral small vessels disease is accompanied by impaired cognitive ability and depressive symptoms, whereby patients with lacunar infarctions have poorer cognition and more severe depressive symptoms than patients with hyper intensive white brain lesions. Also, patients with cerebral small vessels disease who also have metabolic syndrome are more depressed and less cognitively able than patients with cerebrovascular disease but no metabolic syndrome.

Osnovni cilj istraživanja je razvoj metodologije za okvirno vrednovanje uticaja režima padavina na retencioni kapacitet sliva i upravljanje vodama. Formulisana je originalna jednačine za indikator retencionog kapaciteta neizučenog sliva, u funkciji kratkotrajnih jakih kiša i prirodnih karakteristika čiji je uticaj na brzinu i količinu oticaja sa sliva moguće nedvosmisleno kvantifikovati.Ovo je omogućilo vrednovanje indikatora retencionog kapaciteta sliva, lociranje i procena uticaja različitih mera na vrednost indikatora, kao i procenu uticaja predloženih mera na sintetičke jedinične hidrograme. Praktičnost metodologije se ogleda u efikasnosti sagledavanja uticaja predloženih mera, donošenju odluka o njihovoj lokaciji na slivu i primeni. Na ovaj način, dobijen je koristan alat za dobijanje informacija od značaja za donošenje odluka u sektoru voda i ostalim sektorima. The main goal of this research is methodology development for assessment of the rainfall impact on river basin retention capacity and water management. The original equation is developed for the ungauged river basin retention capacity indicator in terms of short-term heavy rainfall and natural features whose influence on the speed and the amount of surface runoff from the basin can be clearly quantified. This enabled the evaluation of the retention capacity indicator, location and evaluation of the effect of different NWRM scenarios, as well as the assessment of the impact of the proposed NWRM to synthetic unit hydrograph. Methodology convenience is reflected in the efficiency of identifying the impact of the proposed measures, decisions on their location in the basin and implementation. In this way, there has been a useful tool obtained for providing the information relevant to decision-making in the water sector and other sectors.

Akutna hiperglikemija se može javiti kod osoba sa ranije dijagnostikovanom šećernom bolesti ili poremećenim metabolizmom glukoze... Acute hyperglycemia has also been documented to occur in people with previously diagnosed diabetes or impaired glucose metabolism...

S obzirom na visoku prevalencu metaboličkog sindroma (10-40% u svetskoj populaciji) i na činjenicu da prisustvo metaboličkog sindroma duplira rizik od nastanka aterosklerotske bolesti kardiovaskularnog sistema jasna je potreba za identifikacijom indivudualnih parametara koji doprinose njenom razvoju. Metabolički sindrom je klaster faktora rizika metaboličkog porekla koji je udružen sa povećanim rizikom za nastanak aterosklerotske bolesti kardiovaskularnog sistema i dijabetes melitusa tipa 2. Insulinska rezistencija, abdominalna gojaznost, aterogena dislipidemija, hipertenzija, proinflamatorno i protrombotično stanje su faktori koji su u osnovi metaboličkog sindroma a često su i praćeni nagomilavanjem masti u jetri. Cilj rada je bio da se utvrdi odnos između markera disfunkcije hepatocita (AST, ALT, GGT), serumskog nivoa inflamatornih biomarkera (broj leukocita, elektroforeza serumskih proteina, CRP, fibrinogen, TNF-α), biomarkera endotelne disfunkcije (ADMA i homocistein), kao i nivoa serumskih adipokina (leptin i adiponektin) i debljine intima-medija kompleksa (IMT) karotidne arterije kao pokazatelja prisustva aterosklerotskog procesa. Ispitivanje je dizajnirano kao studija preseka. U ispitivanje je uključeno 58 ispitanika oba pola sa karakteristikama metaboličkom sindroma (NCEP:ATP III kriterijumi). Odabir ispitanika je vršen u Odeljenju za pravilnu ishranu i zdravstvenu bezbednost hrane, Instituta za javno zdravlje Vojvodine. Kontrolnu grupu su sačinjavale 30 klinički i biohemijski zdravih ispitanika nepušača koji su prema polnoj i dobnoj strukturi odgovarali ispitivanim grupama bolesnika. Iz ispitivanja su isključene osobe koje konzumiraju više od 20g/dan alkohola, pušači, koji imaju dijagnostikovan virusni hepatitis B ili C ili pozitivan Hbs antigen, anti-Hbs antitela i anti-HCV antitela, osobe koje imaju verifikovana oboljenja kardiovaskularnog sistema, bubrega, CNS-a, infektivna, maligna i autoimuna oboljenja kao i druga oboljenja jetre i žučnih puteva, osobe koje su pod medikamentoznom terapijom koja može uticati na nivo serumskih biomarkera endotelne disfunckije, lipidni i lipoproteinski status, glikoregulaciju kao i menstruacioni ciklus. Sve laboratorijske analize su urađene u Centru za laboratorijsku medicinu, Kliničkog centra Vojvodine. Doppler ultrasonografski pregled karotidnih arterija i ultrazvuk abdomena i jetre je urađen u Centru za radiologiju Kliničkog centra Vojvodine. Signifikantna pozitivna korelacija niskog stepena je utvrđena između IMT zajedničke karotidne arterije i serumskih koncentracija GGT, hsCRP i leptina kao i odnosa neutrofili/limfociti. Prema prvom konstruisanom regresionom modelu u kojem je zavisna varijabla bila IMT preko 0,09 cm statistički značajan uticaj na predviđanje debljine IMT zajedničke karotidne arterije imaju hsCRP (Exp (B) 1,112 i glikemija (Exp (B) 1,973). Prema modelu neuronske mreže sa istom zavisnom varijablom najveću mogućnost predviđanja IMT imaju glikemija, AST i fibrinogen. Prema drugom konstruisanom regresionom modelu gde su zavisne varijable bile IMT zajedničke karotidne arterije preko 0,09 cm i prisutnost hepatične steatoze najveću mogućnost predviđanja imaju leptin Exp (B) 1,1022 i ALT Exp (B) 1,053. Prema modelu neuronske mreže sa istom zavisnom varijablom najveću mogućnost predviđanja IMT imaju ALT, ADMA i leptin., Given the high prevalence of metabolic syndrome (10-40% in the world population) and the fact that the presence of metabolic syndrome doubles the risk of atherosclerotic disease of the cardiovascular system, there is a clear need to identify individual parameters that contribute to its development. Metabolic syndrome is a cluster of the risk factors of metabolic origin that is associated with an increased risk for the onset of atherosclerotic disease of the cardiovascular system and type 2 diabetes mellitus. Insulin resistance, abdominal obesity, atherogenic dyslipidemia, hypertension, proinflammatory and prothrombotic conditions are the factors at the base of the metabolic syndrome and are often accompanied by fat accumulation in the liver. The aim of this work was to determine the relation between markers of hepatic dysfunction (AST, ALT and GGT), serum levels of inflammatory biomarkers (white blood cell count, electrophoresis of serum proteins, CRP, fibrinogen, TNF-α), biomarkers of endothelial dysfunction (ADMA and homocysteine) as well as levels of serum adipokines (leptin and adiponectin) and intima-media thickness of carotid artery as indicators of atherosclerotic process in the patients with metabolic syndrome. Study was cross-sectional. It included 58 participants with metabolic syndrome (NCEP:ATP III criteria) as well as 30 clinically and biochemically healthy nonsmokers, age and gender matched controls. Participants were selected in the Department for Nutrition and Food Safety, Center of Hygiene and Human Ecology Institute of Public Health of Vojvodina. Patients that consumed alcohol more than 20g/day were excluded. Participants with positive HBsAg, anti-HBs-antibodies or anti- HCV antibodies were excluded also. Smokers were also excluded. Patients with cardiovascular diseases, renal diseases, infective, hepatic, malignant and autoimmune diseases were excluded from this study. Subjects which used drugs that could affect biomarker levels of endothelial dysfunction, lipid metabolism, glucose metabolism and menstrual cycle were also excluded. All laboratory analyzes were done in Centre for Laboratory Medicine, Clinical Centre of Vojvodina. Doppler ultrasonography of carotid arteries and ultrasound of abdomen and liver were done in Centre for Radiology, Clinical Centre of Vojvodina. Significant positive correlation of low degree was determined between IMT of common carotid artery and serum concentrations between GGT, hsCRP and leptin and relationship neutrophils/lymphocytes. According to the first constructed regression model where dependent variable was IMT of common carotid artery above 0.09 cm statistically significant influence on foreseeing IMT of common carotid artery have hsCRP (Exp (B) 1.112 and glycaemia (Exp (B) 1.973). According to the neuronal network with the same dependent variable greatest probability for foreseeing IMT have glycaemia, AST and fibrinogen. According to the second constructed regression model where dependent variable was IMT above 0.09 cm and present hepatic steatosis greatest probability for foreseeing IMT have leptin Exp (B) 1.1022 and ALT Exp (B) 1.053. According to the neuronal network with the same dependent variable greatest probability for foreseeing IMT have ALT, ADMA and leptin.

S obzirom na visoku prevalencu metaboličkog sindroma (10-40% u svetskoj populaciji) i na činjenicu da prisustvo metaboličkog sindroma duplira rizik od nastanka aterosklerotske bolesti kardiovaskularnog sistema jasna je potreba za identifikacijom indivudualnih parametara koji doprinose njenom razvoju. Metabolički sindrom je klaster faktora rizika metaboličkog porekla koji je udružen sa povećanim rizikom za nastanak aterosklerotske bolesti kardiovaskularnog sistema i dijabetes melitusa tipa 2. Insulinska rezistencija, abdominalna gojaznost, aterogena dislipidemija, hipertenzija, proinflamatorno i protrombotično stanje su faktori koji su u osnovi metaboličkog sindroma a često su i praćeni nagomilavanjem masti u jetri. Cilj rada je bio da se utvrdi odnos između markera disfunkcije hepatocita (AST, ALT, GGT), serumskog nivoa inflamatornih biomarkera (broj leukocita, elektroforeza serumskih proteina, CRP, fibrinogen, TNF-α), biomarkera endotelne disfunkcije (ADMA i homocistein), kao i nivoa serumskih adipokina (leptin i adiponektin) i debljine intima-medija kompleksa (IMT) karotidne arterije kao pokazatelja prisustva aterosklerotskog procesa. Ispitivanje je dizajnirano kao studija preseka. U ispitivanje je uključeno 58 ispitanika oba pola sa karakteristikama metaboličkom sindroma (NCEP:ATP III kriterijumi). Odabir ispitanika je vršen u Odeljenju za pravilnu ishranu i zdravstvenu bezbednost hrane, Instituta za javno zdravlje Vojvodine. Kontrolnu grupu su sačinjavale 30 klinički i biohemijski zdravih ispitanika nepušača koji su prema polnoj i dobnoj strukturi odgovarali ispitivanim grupama bolesnika. Iz ispitivanja su isključene osobe koje konzumiraju više od 20g/dan alkohola, pušači, koji imaju dijagnostikovan virusni hepatitis B ili C ili pozitivan Hbs antigen, anti-Hbs antitela i anti-HCV antitela, osobe koje imaju verifikovana oboljenja kardiovaskularnog sistema, bubrega, CNS-a, infektivna, maligna i autoimuna oboljenja kao i druga oboljenja jetre i žučnih puteva, osobe koje su pod medikamentoznom terapijom koja može uticati na nivo serumskih biomarkera endotelne disfunckije, lipidni i lipoproteinski status, glikoregulaciju kao i menstruacioni ciklus. Sve laboratorijske analize su urađene u Centru za laboratorijsku medicinu, Kliničkog centra Vojvodine. Doppler ultrasonografski pregled karotidnih arterija i ultrazvuk abdomena i jetre je urađen u Centru za radiologiju Kliničkog centra Vojvodine. Signifikantna pozitivna korelacija niskog stepena je utvrđena između IMT zajedničke karotidne arterije i serumskih koncentracija GGT, hsCRP i leptina kao i odnosa neutrofili/limfociti. Prema prvom konstruisanom regresionom modelu u kojem je zavisna varijabla bila IMT preko 0,09 cm statistički značajan uticaj na predviđanje debljine IMT zajedničke karotidne arterije imaju hsCRP (Exp (B) 1,112 i glikemija (Exp (B) 1,973). Prema modelu neuronske mreže sa istom zavisnom varijablom najveću mogućnost predviđanja IMT imaju glikemija, AST i fibrinogen. Prema drugom konstruisanom regresionom modelu gde su zavisne varijable bile IMT zajedničke karotidne arterije preko 0,09 cm i prisutnost hepatične steatoze najveću mogućnost predviđanja imaju leptin Exp (B) 1,1022 i ALT Exp (B) 1,053. Prema modelu neuronske mreže sa istom zavisnom varijablom najveću mogućnost predviđanja IMT imaju ALT, ADMA i leptin. Given the high prevalence of metabolic syndrome (10-40% in the world population) and the fact that the presence of metabolic syndrome doubles the risk of atherosclerotic disease of the cardiovascular system, there is a clear need to identify individual parameters that contribute to its development. Metabolic syndrome is a cluster of the risk factors of metabolic origin that is associated with an increased risk for the onset of atherosclerotic disease of the cardiovascular system and type 2 diabetes mellitus. Insulin resistance, abdominal obesity, atherogenic dyslipidemia, hypertension, proinflammatory and prothrombotic conditions are the factors at the base of the metabolic syndrome and are often accompanied by fat accumulation in the liver. The aim of this work was to determine the relation between markers of hepatic dysfunction (AST, ALT and GGT), serum levels of inflammatory biomarkers (white blood cell count, electrophoresis of serum proteins, CRP, fibrinogen, TNF-α), biomarkers of endothelial dysfunction (ADMA and homocysteine) as well as levels of serum adipokines (leptin and adiponectin) and intima-media thickness of carotid artery as indicators of atherosclerotic process in the patients with metabolic syndrome. Study was cross-sectional. It included 58 participants with metabolic syndrome (NCEP:ATP III criteria) as well as 30 clinically and biochemically healthy nonsmokers, age and gender matched controls. Participants were selected in the Department for Nutrition and Food Safety, Center of Hygiene and Human Ecology Institute of Public Health of Vojvodina. Patients that consumed alcohol more than 20g/day were excluded. Participants with positive HBsAg, anti-HBs-antibodies or anti- HCV antibodies were excluded also. Smokers were also excluded. Patients with cardiovascular diseases, renal diseases, infective, hepatic, malignant and autoimmune diseases were excluded from this study. Subjects which used drugs that could affect biomarker levels of endothelial dysfunction, lipid metabolism, glucose metabolism and menstrual cycle were also excluded. All laboratory analyzes were done in Centre for Laboratory Medicine, Clinical Centre of Vojvodina. Doppler ultrasonography of carotid arteries and ultrasound of abdomen and liver were done in Centre for Radiology, Clinical Centre of Vojvodina. Significant positive correlation of low degree was determined between IMT of common carotid artery and serum concentrations between GGT, hsCRP and leptin and relationship neutrophils/lymphocytes. According to the first constructed regression model where dependent variable was IMT of common carotid artery above 0.09 cm statistically significant influence on foreseeing IMT of common carotid artery have hsCRP (Exp (B) 1.112 and glycaemia (Exp (B) 1.973). According to the neuronal network with the same dependent variable greatest probability for foreseeing IMT have glycaemia, AST and fibrinogen. According to the second constructed regression model where dependent variable was IMT above 0.09 cm and present hepatic steatosis greatest probability for foreseeing IMT have leptin Exp (B) 1.1022 and ALT Exp (B) 1.053. According to the neuronal network with the same dependent variable greatest probability for foreseeing IMT have ALT, ADMA and leptin.

Uvod: Dijabetesno stopalo je hronična komplikacija dijabetes melitusa (DM) koja nastaje usled strukturalnih i funkcionalnih poremećaja stopala. Ono predstavljaznačajan problem kod obolelih od dijabetes melitusa zbog sklonosti ka nastanku ulceracija, infekcija ili oštećenja mekih tkiva stopala, a pogađa skoro polovinu obolelih kod kojih bolest traje duže od 10 godina kao i one obolele koje imaju dijabetesnu perifernu neuropatiju. Dijabetes melitus danas u svetu dobija razmere pandemije i uzrok je 8 od 10 netraumatskih amputacija. Mortalitet nakon amputacije kreće se od 39% do 80% za 5 godina, što je lošije nego za većinu malignih bolesti. Ovom studijom je izvršeno poređenje dijagnostičkih test karakteristika statičkog i dinamičkog merenja plantarnih pritisaka u odnosu na test karakteristike monofilamentom kod pacijenata sa dijabetes melitusom i dijabetesnim stopalom. Metodologija:Sprovedena je opservaciona studija preseka između pacijenata sa dijabetesnim stopalom i kontrolne grupe zdravih dobrovoljaca pregledanih u KC Kragujevac, u periodu od juna 2014. do decembra 2014.godine. Studija je obuhvatila 130 ispitanika podeljenih u dve grupe, i urađeno je 1560 merenja pedografom. Sva merenja obavljena su u toku jedne posete i pored anamneze i antropometrijskih merenja, vitalnih znakova, kliničkog neuropatskog skora (KNS) 1-4, testa monofilamentom (10g) u 10 tačaka, test vibracionog senzibiliteta (zvučna viljuška 128Nѕ), urađena su i merenja na pedografu ”FOOTWORK PRO”- platformi. Mereni su pritisci i raspodele sile tokom stajanja i hoda. Određen je stepen korelacije između mesta maksimalnih i srednjih pritisaka oba merenja i rezultata testa monofilamentom sa kliničkim promenama na stopalima uočenim pri kliničkom pregledu i zabeleženih na skicama i fotografijama. Rezultati:Statičko i dinamičko merenje plantarnih pritisaka zajedno sa testom monofilamentom, u odnosu samo na test monofilamentom, omogućava značajno bolju ranu dijagnostiku dijabetesnog stopala. Od sva tri navedena testa dinamički model merenja je bio u najboljoj korelaciji sa kliničkim nalazom i to u 95.54%. Ispitivanjem svih parametara dinamičkog modela merenja u projekciji III MT kosti za oba stopala, najveću površinu ispod krive ima integral pritisak/vreme ( AUC 0.684, SE 0,035 CI 0.614

Osobe obolele od dijabetes melitusa imaju veću incidencu i mortalitet od tumora. Prethodne studije su pokazale da oksidativni stres, koji nastaje kao posledica hiperglikemije, ubrzava metastaziranje. U ovom istraživanju dijabetes je indukovan jednom visokom dozom streptozotocina u cilju ispitivanja uticaja dijabetes melitusa na rast tumora i modulaciju antitumorskog imunskog odgovora, u modelu 4T1 karcinoma dojke u BALB/c miševa. Dijabetes melitus je ubrzao pojavu, rast i masu primarnog tumora što je praćeno smanjenom citotoksičnošću NK ćelija prema 4T1 ćelijama, in vitro. Dijabetes melitus je značajno smanjio procentualnu zastupljenost NKG2D+, perforin+, granzim+, IFN-γ+ i IL-17+ NK ćelija, dok je povećao ekspresiju PD-1 molekula i produkciju IL-10 u NK ćelijama u slezini. Dijabetes je značajno smanjio procenat NKG2D+ NK ćelija i povećao procenat PD-1+ NK ćelija i u primarnom tumoru. Dijabetično stanje je povećalo akumulaicju IL-10+ Tregs i TGF-β+ mijeloidnih supresorskih ćelija (MDSCs) u slezini i primarnom tumoru. Dijabetični serum je u in vitro uslovima značajno povećao procenat KLRG-1+ i PD-1+ NK ćelija, smanjio procenat IFN-γ+ NK ćelija, ekspresiju NKp46 i produkciju perforina, granzima, CD107a i IL-17 u NK ćelijama u poređenju sa serumom kome je dodata glukoza odnosno sa kontrolnim serumom. Dijabetes melitus je značajno povećao ekspresiju inducibilne azot monoksid sintaze (iNOS) i indolamin 2,3-dioksigenaze (IDO) u slezinskim MDSCs i dendritskim ćelijama (DC) miševa pre indukcije tumora. Specifični inhibitor indolamin 2,3-dioksigenaze, 1-metil-DL- triptofan, je gotovo u potpunosti povratio fenotip NK ćelija kultivisanih u dijabetičnom serumu. Ovi rezultati ukazuju da dijabetes melitus ubrzava rast tumora povećanom akumulacijom imunosupresivnih ćelija i supresijom NK ćelija aktivnošću enzima IDO. Diabetic patients have higher incidence and mortality of cancer. Recent study revealed that hyperglycemiainduced oxidative stress is involved in the acceleration of tumor metastasis. We used model of high dose streptozotocin-induced diabetes to investigate its effect on tumor growth and modulation of antitumor immune response of 4T1 murine breast cancer in BALB/c mice. Diabetes accelerated tumor appearance, growth and weight, which was associated with decreased NK cells cytotoxicity against 4T1 tumor cells in vitro. Diabetes reduced frequencies of systemic NKG2D+, perforin+, granzyme+, IFN-γ+ and IL-17+ NK cells, while increased level of PD-1 expression and production of IL-10 in NK cells. Diabetes decreased percentage of NKG2D+NK cells and increased percentage of PD-1+ NK cells also in primary tumor. Diabetes increased accumulation of IL-10+ Tregs and TGF-β+ myeloid derived suppressor cells (MDSCs) in spleen and tumor. Diabetic sera in vitro significantly increased percentage of KLRG-1+ and PD-1+ NK cells, decreased percentage of IFN-γ+NK cells, expression of NKp46 and production of perforin, granzyme, CD107a and IL-17 per NK cell in comparison to glucose added mouse sera and control sera. Significantly increased percentages of inducible nitric oxide synthase (iNOS) and indoleamine 2,3-dioxygenase (IDO) producing MDSCs and dendritic cells (DC) were found in the spleens of diabetic mice prior to tumor induction. 1-methyl-DLtryptophan, specific IDO inhibitor, almost completely restored phenotype of NK cells cultivated in diabetic sera. These findings indicate that diabetes promotes breast cancer growth at least in part through increased accumulation of immunosuppressive cells and IDO mediated attenuation of NK cells

Ulcerozni kolitis (engl. Ulcerative colitis- UC) je hronično oboljenje koje karakteriše zapaljenje sluznice digestivnog trakta, prvenstveno debelog creva. Metabolički sindrom je čest poremećaj značajno povezan sa UC. Veliki broj studija je pokazao značajan komorbiditet ovih poremećaja i njihovu genetsku povezanost. Cilj studije bio je da se ispita povezanost razvojnih faza metaboličkog sindroma sa težinom bolesti, te lokalnim i sistemskim imunskim odgovorom kod pacijenata sa ulceroznim kolitisom. Kod ispitanika sa ulceroznim kolitisom i metaboličkim sindromom zabeležena je klinički i patohistološki blaža bolest sa sistemskom i lokalnom predominacijom galektina 1, galektina 3 i imunosupresivnog citokina IL-10, uz sniženu koncentraciju proinflamacijskih citokina TNF-α, IL-6 i IL-17. Takođe je registrovana manja zastupljenost CD8+ T limfocita, a veća zastupljenost regulatornih CD4+Foxp3+ limfocita, kao i veća ekspresija galektina-3 na limfocitima i veća produkcija imunosupresivnog IL-10 u lamina propria-i obolelih od ulceroznog kolitisa sa metaboličkim sindromom. Kod ispitanika u terminalnoj fazi metaboličkog sindomoma zabeležena je klinički i patohistološki teža forma ulceroznog kolitisa. U ovoj grupi ispitanika nađena je sistemska i lokalna predominacija proinflamacijskih citokina TNF-α, IL-6 i IL-17 nad galektinom-1, galektina-3 nad proinflamacijskim medijatorima TNF-α i IL-17 kao i povećana ekspresija galektina-3 na imunokompetentnim ćelijama koje infiltrišu lamina propria-u. Lokalna i sistemska predominacija Gal-1 i Gal-3 nad proinflamacijskim citokinima kod obolelih sa metaboličkim sindromom može predstavljati mehanizam zaustavljanja i ograničavanja proinflamacijskog procesa i sprečiti oštećenje tkiva, ukazujući na imunosupresivnu ulogu Gal-1 i Gal-3 u biologiji ulceroznog kolitisa kod bolesnika sa metaboličkim sindromom. Sistemska i lokalna predominacija proinflamacijskih citokina TNF-α, IL-6 i IL-17 nad Gal-1 i Gal-3 u terminalnoj fazi metaboličkog sindroma pojačava zapaljenje i sledstveno oštećenje tkiva. Ulcerative colitis (UC) is a chronic disease characterized by inflammation of intestinal epithelium, primarily of the colon. Metabolic syndrome is a common disorder significantly associated with UC. A large number of studies have shown significant comorbidity of these disorders and their genetic linkage. The aim of the study was to examine the relationship between the developmental stages of the metabolic syndrome with the severity of the disease, and the local and systemic immune response in patients with ulcerative colitis. Clinical and pathohystologically mild disease with systemic and local prevalence of galectin 1, galectin 3 and immunosuppressive cytokine IL-10 was observed in subjects with ulcerative colitis and metabolic syndrome, with reduced concentration of proinflammatory cytokines TNF-α, IL-6, and IL-17. Further, we detected lower incidence of CD8+ T lymphocytes and enhanced accumulation of regulatory CD4+ Foxp3+ T cells, as well as increased expression of galectin-3 on lymphocytes and higher production of immunosuppressive IL-10 in lamina propria derived from UC patients with metabolic syndrome. Clinical and pathohystologically severe disease was observed in the patients with terminal phase of the metabolic syndrome. In this group of subjects, we found systemic and local prevalence of proinflammatory cytokines TNF-α, IL-6, and IL-17 over galectin-1; galectin-3 over TNF-α and IL-17; as well as increased expression of galectin-3 on immunocompetent cells infiltrating the lamina propria. Local and systemic dominance of Gal-1 and Gal-3 over proinflammatory cytokines in patients with metabolic syndrome may present a mechanism for stopping and limiting the proinflammatory process and preventing tissue damage, indicating the immunosuppressive role of Gal-1 and Gal-3 in the ulcerative colitis biology of patients with metabolic syndrome. Systemic and local prevalence of proinflammatory cytokines TNF-α, IL-6, and IL-17 over Gal-1 and Gal-3 in the terminal phase of the metabolic syndrome enhances inflammation and consequent tissue damage.

Diabetic nephropathy is one of the leading cause of chronic kidney disease and end-stage renal disease. It occurs in 20-40% patients with diabetes mellitus, and microalbuminuria is still considered as the first sign of diabetic nephropathy. Low sensitivity and specificity of microalbuminuria leads to more sensitive biomarkers that may be used to detect diabetic nephropathy at an earlier stage with higher accuracy. This study was carried out to determine whether urinary biomarkers such as collagen type IV, transferrin and L-FABP can serve as an indicator of diabetic nephropathy. The study included 80 diabetic adult patients who were classified into two groups: group 1 - normoalbuminuric patients (albumin excretion up to 30 mg/d), group 2 – microalbuminuric patients (albumin excretion from 30-300 mg/d) and 10 healthy controls. In our group, 44 (55%) patients were male and 36 (45%) female, mean age 59.85± 8.87 years. Prevalence of microalbuminuria was 41.25% (33 patients) and 58.75% were normoalbuminuric (47 patients). During the trial, urinary biomarker concentrations were found to be significantly higher in patients with microalbuminuria compared with patients who were normoalbuminuric. There was no statistically significant difference in the level of urinary biomarkers compared to glycoregulation, body weight index, and duration of diabetes. The results of this study have shown that collagen type IV, transferrin and L-FABP in 24 hours and the first morning urine are sensitive and specific tests for early diagnosis of diabetic nephropathy. Among them, the greatest sensitivity and specificity was shown by urinary transferrin. Although there was a correlation between urinary transferrin concentration and diabetic retinopathy.

UVOD: Procesi koji obuhvataju endotelnu disfunkciju, oksidativni stres, hroničnu inflamaciju, hiperaktivnost i aktivaciju trombocita te narušavanje ravnoteže procesa koagulacije i fibrinolize od najranijih faza razvoja dijabetes melitusa tip 2 (T2DM) promovišu aterogenezu i nastanak aterotromboznih komplikacija. Kompleksan terapijski pristup u T2DM ima za cilj ne samo uspostavljanje glikoregulacije, korekciju brojnih metaboličkih poremećaja i modifikaciju pridruženih faktora rizika za nastanak ateroskleroze već i primenu antitrombocitne terapije u cilju primarne ili sekundarne prevencije aterotromboznih komplikacija. Uprkos primenjenoj antiagregacionoj terapiji, deo bolesnika doživi rekurentne aterotrombozne atake. Bolesnici sa T2DM se izdvajaju kao grupa sa posebnim rizikom za recidivantne aterotromboze što može biti uslovljeno rezistencijom na primenjenu antitrombocitnu terapiju. Praćenje efekata antitrombocitne terapije i blagovremeno identifikovanje rezistentnih bolesnika ima za cilj optimizaciju primenjene antitrombocitne terapije što može biti od izuzetnog kliničkog značaja u smislu sprečavanja progresije aterotromboznog procesa. CILJ: Proceniti i uporediti nivoe biomarkera, pokazatelja endotelne aktivacije, aktivacije i agregabilnosti trombocita u bolesnika sa bolešću arterijskih krvnih sudova u tipu 2 dijabetes melitusa u odnosu na njihove vrednosti u zdravoj populaciji. Uporediti efikasnost primenjene antitrombocitne terapije tienopiridinima u bolesnika sa tipom 2 dijabetes melitusa i bolešću arterijskih krvnih sudova u odnosu na efikasnost ove terapije u nedijabetičnoj populaciji bolesnika sa bolešću arterijskih krvnih sudova. MATERIJAL I METODE: U ispitivanje je uključeno 100 ispitanika oba pola, starosti od 33 do 70 godina života, kod kojih je prethodno utvrđeno postojanje neke od kliničkih manifestacija bolesti arterijskih krvnih sudova (IBS, CVB, PAB) koji kao antitrombocitnu terapiju uzimaju tienopiridinski preparat, klopidogrel. Od toga, 50 uključenih ispitanika imalo je dijagnozu dijabetes melitus tipa 2, a 50 su bili bolesnici bez dijabetesa. Kontrolnu grupu je činilo 30 klinički i biohemijski zdravih ispitanika, nepušača koji su prema polnoj i dobnoj strukturi odgovarali ispitivanim grupama bolesnika. Svim ispitanicima su urađena antropometrijska merenja, laboratorijska analiza uzoraka krvi na automatizovanim analizatorima sa određivanjem parametara metabolizma glukoze, lipida, parametera inflamacije, KKS, parmetara koagulacije i trombocitnih pokazatelja. Određivanje serumske koncentracije sE–selektina i sP-selektina je vršeno ELISA tehnikom (R&D Systems, Inc. Minneapolis, USA). Plazmatska koncentracija vWFAg-a određivana je imunoturbidimetrijskom metodom na koagulacionom analizatoru Siemens Healthcare Diagnostics, Nemačka. Agregabilnost trombocita je određivana impedantnom agregometrijom (Multiple Electrode Aggregometry - MEA) na Multiplate analizatoru, Dynabyte, Minhen, Nemačka. Bazalna agregabilnost trombocita procenjivana je TRAP testom, rezidualna agregabilnost trombocita pod terapijom klopidogrela ADP testom, rezidualna agregabilnost trombocita pod terapijom aspirina, ASPI testom. Individualni odgovor na primenjenu antiagregacionu terapiju je procenjivan i na osnovu procenta sniženja bazalne agregabilnosti trombocita (%SAT) nakon primenjene antiagregacione terapije što je izračunato sledećim formulama: procena antiagregacionog efekta klopidogrela:%SATadp =100 x (1-ADP/TRAP) i procena antiagregacionog efekta aspirina:%SATaspi =100 x (1-ASPI/TRAP). REZULTATI: Nivo sE-slektina je bio signifikantno viši u bolesnika sa T2DM u odnosu na bolesnike bez dijabetesa (45,1±18,1vs.31,8±10,5ng/ml; p, INTRODUCTION: Processes involving endothelial dysfunction, oxidative stress, chronic inflammation, platelet activation and the imbalance between coagulation and fibrinolysis promote atherogenesis and atherothrombotic complications at early stage of diabetes mellitus type 2 (T2DM). The complex therapeutic approach in T2DM aims not only to reestablish glycemic control and to correct a number of metabolic disorders, but also to achieve primary or secondary prevention of atherothrombotic complications. Despite the applied antiplatelet therapy, some patients experience recurrent atherothrombotic attacks. Patients with T2DM are the group at particular risk for recurrent atherothrombosis, which can be caused by antiplatelet therapy resistance. Monitoring the effectiveness of antiplatelet therapy and identification of resistant patients aims to optimize the applied antiplatelet therapy, which can be of great clinical significance in terms of preventing progression of atherotrombotic processes. AIM: Evaluate and compare the levels of biomarkers, indicators of endothelial activation, platelet activation and aggregability in patients with arterial vascular disease in type 2 diabetes mellitus compared to their values in a healthy population. Compare the effectiveness of applied antiplatelet therapy with thienopyridines in patients with type 2 diabetes mellitus and arterial vascular disease compared to the efficacy of this therapy in nondiabetic population of patients with arterial vascular disease. MATERIAL AND METHODS: The study included 100 patients, 33 to 70 years of age, with previously established existence of some of the clinical manifestations of arterial vascular disease (CAD, CVD, PAD), taking thienopyridine antiplatelet therapy with clopidogrel. 50 patients was previously diagnosed with diabetes mellitus type 2 and 50 were nondiabetic patients. Control group included 30 age and sex matched healthy participants, non-smokers. All subjects underwent anthropometric measurements and laboratory analysis of blood samples on automated analyzers with determining the parameters of glucose metabolism, lipids, inflammation parameters, complete blood count, coagulation and platelet parameters. Serum concentrations of sEselectin and sP-selectin were determined by ELISA (R&D Systems, Inc., Minneapolis, USA). vWFAg was determined by immunoturbidimetry on coagulometer Siemens Healthcare Diagnostics, Germany. Platelet aggregability was determined by impedance aggregometry (Multiple Electrode Aggregometry - MEA) on Multiplate analyzer, Dynabyte, Munich, Germany. Basal platelet aggregability was estimated by TRAP test, residual platelet aggregability during clopidogrel treatment was estimated by ADP test and during aspirin treatement by ASPI test. Individual response to antiplatelet therapy was estimated by the percentage of decrease in basal platelet aggregability (%DPA) obtained after antiplatelet therapy, calculated bypresented formulas: %DPAadp =100 x (1-ADP/TRAP)and %DPAaspi =100 x (1- ASPI/TRAP). RESULTS: Concentration of sE-selectin was significantly higher in patients with T2DM in order to non-diabetic patients (45,1±18,1vs.31,8±10,5ng/ml;p

Psorijaza pogađa 2-3% svetske populacije i kao sistemsko hronično zapaljensko oboljenje praćena je brojnim komorbiditetima koji utiču i na preživljavanje bolesnika. Oboleli od psorijaze imaju kraći životni vek usled povećanog rizika od kardiovaskularnih oboljenja, šećerne bolesti i metaboličkog sindroma. Istraživanje je dizajnirano kao prospektivna studija preseka kojom su upoređivani testirani parametri u grupi obolelih od psorijaze (66 ispitanika) i kontrolnim grupama obolelih od ekcema (20 ispitanika) i zdravih kontrola (20 ispitanika). Isključeni su oboleli od psorijaze i ekcema sa ranije dijagnostikovanim ili aktuelnim kardiovaskularnim, metaboličkim ili drugim sistemskim bolestima, takođe ni bolesnici lečeni sistemskom terapijom. Svi ispitanici bili su između 18 i 60 godina života. Ispitivani su antropomentrijski, epidemiološki i klinički podaci, laboratorijski parametri inflamacije, hiperkoagulabilnosti, kardiovaskularnog rizika, lipidnog statusa, metabolizma glukoze, parametri bubrežne funkcije, ultrasonografski prediktori subkliničke ateroskleroze na perifernim arterijama i srcu. Rezultati su diskutovani u svetlu različitih, podataka o vezi psorijaze i ekcema sa aterosklerozom i ostalim kardiometaboličkim stanjima. Rezultati istraživanja su sadržani u sledećim zaključcima: 1. Rani ultrasonografski prediktori za razvoj subkliničke ateroskleroze predstavljeni debljinom intime medije karotidne i femoralne arterije su u korelaciji sa psorijazom, ali ne sa ekcemom. Psorijaza predstavlja nezavisan faktor rizika za razvoj subkliničke ateroskleroze na osnovu multivarijantne analize, jer najvažniji prediktor za debljinu intime medije karotidne i femoralne arterije predstavlja psorijaza sama po sebi. 3. Povećane koncentracije biomarkera inflamacije i metaboličkih poremećaja su u korelaciji sa psorijazom, ali ne sa ekcemom. 4. Veća je učestalost metaboličkog sindroma kod obolelih od psorijaze u odnosu na kontrolne grupe. 5. Postoji pozitivna korelacija između stepena aktivnosti psorijaze izražene PASI skorom sa koncentracijom biomarkera inflamacije i metaboličkih poremećaja i ehokardiografskim prediktorima, ali ne i sa ultrasonografskim znacima rane ateroskleroze na perifernim i renalnim arterijama. 6. Smanjena brzina protoka u brahijalnoj arteriji kod obolelih od psorijaze ukazuje na mogućnost povećanog rizika za nastanak koronarne bolesti. 7. Ehokardiografski prediktori za razvoj srčane disfunkcije nađeni su kod obolelih od psorijaze u većoj učestalosti u odnosu na kontrolne grupe. Psorijaza je u korelaciji sa povećanim koncentracijama biomarkera inflamacije i metaboličkih poremećaja, te doprinosi razvoju sistemske ateroskleroze, kao i nastanku kardiovaskularnih i metaboličkih oboljenja i nameće potrebu za identifikacijom obolelih sa ovim rizicima. Psoriasis affects 2-3% of the world's population and as a systemic chronic inflammatory disease is associated with many comorbidities that affects on the survival of patients. People with psoriasis have a shorter life expectancy due to increased risk of cardiovascular disease, diabetes and metabolic syndrome. The study was designed as a prospective cross-sectional study that tested parameters were compared in a group of psoriasis patients (66 subjects) and control groups of patients with eczema (20 subjects) and healthy controls (20 subjects). Excluded are suffering from psoriasis and eczema with previously diagnosed or current cardiovascular, metabolic or other systemic diseases, and neither do patients treated with systemic therapy. All subjects were between 18 and 60 years of age. They were evaluated for antropometric, epidemiological and clinical data, laboratory parameters of inflammation, hypercoagulability, cardiovascular risk, lipid status, metabolism of glucose, the parameters of renal function, ultrasonography predictors of subclinical atherosclerosis in peripheral arteries and heart. The results are discussed in the light of various data regarding psoriasis and eczema with atherosclerosis and other cardiometabolic conditions. The research results are contained in the following conclusions: 1. Early ultrasonographic predictors for the development of subclinical atherosclerosis represented intima media thickness of the carotid and femoral artery correlated with psoriasis, but not with eczema. Psoriasis is an independent risk factor for the development of subclinical atherosclerosis based on multivariate analysis, because the most important predictor of intima media thickness of the carotid and femoral artery represents psoriasis itself. 3. Increased concentrations of biomarkers of inflammation and metabolic disorders correlated with psoriasis, but not with eczema. 4. Increased frequency of the metabolic syndrome in psoriasis patients as compared to control groups. 5. There is a positive correlation between level of psoriasis activity expressed in PASI score and serum biomarkers of inflammation and metabolic disorders, and echocardiographic predictors, but not with ultrasonographic signs of early atherosclerosis on peripheral and renal arteries. 6. The reduced flow in the brachial artery in patients with psoriasis indicates the possibility of an increased risk for coronary artery disease. 7. Echocardiographic predictors for developement of cardiac dysfunction have been found more frequently in patients suffering from psoriasis compared to the control groups. Psoriasis is correlated with increased concentrations of biomarkers of inflammation and metabolic disorders, and to contribute to the development of systemic atherosclerosis, which all together represent predictors of cardiovascular and metabolic diseases and imposes the need for identification of patients with these risks.

Spatial plans in Croatia have been drafted digitally since the adoption of the “Ordinance on the content, criteria for map projections, required spatial indicators and the standards of physical planning studies” in 1998, which regulated, among other, types of maps comprised in a plan, map content and symbology. It was a big step forward in comparison to manual drafting of the plans. However, since the Ordinance allows the introduction of custom themes and does not prescribe a data model that would uniformly describe graphical data, over the course of its application it has become next to impossible to integrate all plans and exhibit them in one place, not to speak of carrying out any coherent spatial analysis. In order to straighten up our physical planning system, i.e. to allow easy access and “reading” the plans by the broad public, the ISPU (Physical Planning Information System) has been under development as the central physical planning portal, along with its modules, which are separate applications, each one of them intended to fulfil a task prescribed by law. The most important are the eDozvola (ePermit) module for the issuance of building and other permits in accordance with the provisions of the 2013 Building Act, and the ePlanovi (ePlans) module, which is a web application for loading and editing the new generation of spatial plans, as well as for keeping track of the legality of the process of development and adoption of the plans. In this paper we will shortly present realized and planned functionalities of the ISPU and the ePlanovi module based on GIS technology and how it will enable accessibility, viewing and understanding of the spatial plans.

Teško je razlikovati paratireoidne karcinome (PC) od paratireoidnih adenoma samo na osnovu histopatoloških 100 karakteristika. Na osnovu postojeće literature, ova doktorska disertacija je prva koja istražuje ekspresiju CD105 (endoglina) u angiogenim endotelnim ćelijama PC. CD 105 antitela su pogodna u određivanju mikrovaskularne gustine (MVD). Ki67 se koristi kao marker ćelijske proliferacije. Određivanje ekspresije markera ćelijske proliferacije (Ki67) i neoangiogeneze (CD 105) i njihove povezanosti sa serumskim nivoima PTH i klasičnim prognostičkim parametrima paratiroidnih adenoma i karcinoma. MATERIJAL I METODE: Retrospektivna analiza sprovedena je na 50 bolesnika kod kojih je patohistološki potvrđen primarni hiperparatiroidizam: 10 pacijenata obolelih od karcinoma paratiroidne žlezde i 40 od adenoma. Normalne paratiroidne žlezde su korišćene kao kontrolna grupa. U standardnoj imunohistohemijskoj proceduri, monoklonska antitela endoglina su primenjena za detekciju angiogenih endotelnih ćelija. Imunološko bojenje je procenjeno analizom slike i statistička analiza je kasnije izvršena. REZULTATI: Zaključeno je da Ki67 bio viši u PC pacijenata (medijana = 523,43) u poređenju sa pacijentima obolelim od adenoma (medijana = 297,41). Mann–Whitney U testom dobijena je visoko statistički značajna razlika između ove dve grupe (U = 10.50; Z = 4.598; p < 0.001). MVD bila je veća u PC pacijenata (medijana = 901,14) u odnosu na pacijenate obolele od adenoma (medijana = 431.24). Mann–Whitney U testom dobijena je takođe visoko statistički značajna razlika između grupa (U = 41,50; Z = 3,845; p < 0,001). U ovoj studiji, ekspresija endoglin nije pronađena u krvnim sudovima normalnih 101 paratireoidnih žlezda. Iz ROC krive se može videti da oba markera imaju dobru prediktivnu vrednost za dijagnozu karcinoma. Pokazana je i njihova korelacija sa ostalim obeležjima. Zaključili smo da je serumski nivo preoperativnog PTH koristan za predikciju paratiroidnih karcinoma i da on visoko statistički značajno koreliše još sa težinom tumora, sa promerom tumora, sa vrednostima Ca preoperativno i sa Ki-67 i MVD. Veličina paratiroidnih tumora može biti važan faktor u predviđanju paratiroidnih karcinoma kod pacijenata sa primarnim hiperparatiroidizmom. Takođe, smo utvrdili da je veća verovatnoća da bolesnik sa velikom težinom tumora ima karcinom nego adenom. ZAKLjUČAK: Primećeno je u studiji da postoji veća stopa angiogeneze i ćelijske proliferacije u malignim tumorima u odnosu na benigne, što ukazuje na ulogu ovih tumora u malignitetu i agresivnijem ponašanju. Štaviše, ekspresioni profili biomarkera Ki67 i CD105 u ovoj studiji predstavljaju potencijalne markere maligniteta ili ciljeve nove terapije u bolesnika sa karcinomom paratiroidne žlezde (PC). INTRODUCTION: It is difficult to distinguish parathyroid carcinoma (PC) from parathyroid adenoma on the basis of histopathological features alone. As far as is known to the authors based on the existing literature, the present study 105 is the first to investigate CD105 (Endoglin) expressed in angiogenic endothelial cells of PC. CD 105 antibodies are suitable in determining microvessel density (MVD). Ki67 is used as a marker for cell proliferation. AIM: To determine expression of two markers of cell proliferation (Ki67) and their angiogenesis (CD 105 ) and as well as correlation with serum PTH levels and classic prognostic parameters of parathyroid adenoma and carcinoma. MATERIALS AND METHODS: A retrospective analysis of 50 patients who have pathologically confirmed primary hyperparathyroidism (PHPT) was conducted: 10 patients suffering from PC and 40 patients suffering from adenoma. Normal parathyroid glands served as the control group. In a standard immunohistochemical procedure, monoclonal antibodies to Endoglin, were applied to detect angiogenic endothelial cells. Immunostaining was estimated through image analysis and a statistical analysis was subsequently performed. RESULTS: It was concluded that Ki67 was higher in PC patients (median= 523.43) compared to adenoma patients (median = 297.41). A Mann–Whitney U-test shows the difference to be significant between the two groups (U = 10.50; Z = 4.598; p < 0.001). MVD was higher in PC patients (median= 901.14) than in adenoma patients (median = 431.24). A Mann–Whitney U-test also has shown the difference to be significant (U = 41.50; Z = 3.845; p

Nealkoholna masna bolest jetre (NAFLD) obuhvata različit spektar bolesti, od jednostavne steatoze koja predstavlja akumulaciju masti u jetri, preko nealkoholnog steatohepatitisa (NASH), pa do ciroze i mogućeg nastanka hepatocelularnog karcinoma i usko je povezana sa gojaznošću i šećernom bolešću tip 2. Galektin-3 je multifunkcionalni β-galaktozid-vezujući lektin eksprimiran u različitim ćelijama, kako imunskog sistema tako i ćelijama drugih tkiva i organa. U zavisnosti od lokalizacije i bolesti može ispoljiti kako proinflamatorne, tako i antiinflamatorne karakteristike. Uloga galektina-3 u razvoju masne bolesti jetre indukovane gojaznošću nije do kraja objašnjena. U cilju ispitivanja uloge galektina-3 u razvoju NASH-a i fibroze jetre, galektin-3 deficijentni (LGALS3-/-) i miševi divljeg soja na C57Bl/6 podlozi (LGALS3+/+), stavljeni su na ishranu sa visokim sadržajem masti (60% kcal od masti) ili standardnu ishranu (10% kcal od masti) u trajanju od 12 odnosno 24 nedelje. Delecija gena za galektin-3 ubrzava nastanak gojaznosti indukovane dugotrajnom ishranom sa visokim sadržajem masti i praćena je izraženijom masnom infiltracijom u jetri. Izraženija steatoza u jetri praćena je većom ekspresijom gena uključenih u transport i metabolizam masti PPAR-γ, CD36 i FAS-a. Suprotno, galektin-3 pozitivni miševi su imali veće hepatocelularno oštećenje, inflamaciju i fibrozu koja je bila praćena većim brojem zrelih dendritičnih ćelija, proinflamatornih CD11b+Ly6Chi monocitno/makrofagnih ćelija u jetri, perifernoj krvi i kostnoj srži, kao i većom ekspresijom CCL2, F4/80, CD11c, TLR4, CD14, NLRP3 inflamazoma, IL-1β i komponenti NADPH-oksidaznog sistema u jetri. Uprkos izraženijoj steatozi, gojazni galektin-3 deficijentni miševi nisu razvili fibrozni NASH. Dodatno, veće hepatocelularno oštećenje gojaznih galektin-3 pozitivnih miševa praćeno je većom ekspresijom IL-33 u hepatocitima, kao i većom zastupljenošću mijeloidnih CD11b+IL-13+ ćelija i većom ekspresijom gena za IL-33, ST2 i IL-13 u jetri u poređenju sa LGALS3-/- miševima. Peritonealni makrofagi galektin-3 deficijentnih miševa u odgovoru na stimulaciju IL-33 in vitro eksprimiraju manje ST2 i produkuju manje IL-13. Manji stepen fibroze jetre u galektin-3 deficijentnih miševa praćen je manjom ekspresijom ST2 kao i manjom produkcijom IL-13 u CD11b+ makrofagama nakon aplikacije rekombinantnog IL-33 in vivo. Zaključak sprovedene studije je da galektin-3 igra veoma važnu regulatornu ulogu u IL-33/ST2/IL-13 zavisnoj fibrozi jetre. Non-alcoholic fatty liver disease (NAFLD) which encompasses simple steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis, and possibly liver carcinoma is strongly associated with obesity and type 2 diabetes mellitus. Galectin-3 is a multifunctional β-galactoside–binding lectin expressed by a variety of cell types, exerts both pro- and anti-inflammatory roles depending on localisation and disease condition.The importance of Galectin-3 in obesity-associated liver pathology is incompletely defined. In order to dissect the role of Gal-3 in fibrotic nonalcoholic steatohepatitis (NASH), Gal-3-deficient (LGALS3-/-) and wild-type (LGALS3+/+) C57Bl/6 mice were placed on obesogenic high-fat diet (HFD, 60% kcal fat) or standard chow diet for 12 and 24 weeks. Compared to WT mice, HFD-fed LGALS3-/- mice developed, in addition to increased visceral adiposity and diabetes, marked liver steatosis. Liver steatosis was accompanied with higher expression of hepatic PPAR-γ, CD36 and FAS. However, as opposed to LGALS3-/- mice, hepatocellular damage, inflammation and fibrosis were more extensive in WT mice which had elevated number of mature myeloid dendritic cells, proinflammatory CD11b+Ly6Chi monocytes/macrophages in liver, peripheral blood and bone marrow, and increased hepatic CCL2, F4/80, CD11c, TLR4, CD14, NLRP3 inflammasome, IL-1β and NADPH-oxidase enzymes mRNA expression. Thus, obesity-driven greater steatosis was uncoupled with attenuated fibrotic NASH in Gal-3 deficient mice. HFD-fed WT mice had higher number of hepatocytes that strongly expressed IL-33 and hepatic CD11b+IL-13+ cells, increased levels of IL-33 and IL-13 and upregulated IL-33, ST2 and IL-13 mRNA in liver compared to LGALS3-/- mice. IL-33 failed to induce ST2 upregulation and IL-13 production by LGALS3-/- peritoneal macrophages in vitro. In vivo administration of IL-33 enhanced liver fibrosis in HFD-fed mice in both genotypes, albeit to a significantly lower extent in LGALS3-/- mice which was associated with less numerous hepatic IL-13 expressing CD11b+ cells. The present study provides evidence of a novel role for Gal-3 in regulating IL-33/ST2/IL-13 dependent liver fibrosis.

Difuzni B krupnoćelijski limfom kao najčešći tip nehočkinskih limfoma, čini heterogenu grupu oboljenja sa višestrukim genetskim abnormalnostima. Posebno su značajna oštećenja gena koji učestvuju u kontroli ćelijskog ciklusa i apoptozi. Udruženost bcl-2/c-myc genskog preuređenja, čini oko 60% Double-Hit limfoma, bez mnogo podataka o prognostičkom značaju. Ciljevi ove studije bili su da se FISH-om ispita uticaj genskog polimorfizma bcl-2+ i c-myc+ na terapijski odgovor, kao i da se ispita mogućnost da se prema internacionalnom prognostičkom indeksu (IPI) selektuju bolesnici za testiranje čime bi se individualizovao terapijski pristup. Rezultati studije su pokazali da genski polimorfizam bcl-2+ i c-myc+, pojedinačan i udružen, ne utiče značajno na preživljavanje, međutim pokazuje lošiji odgovor na terapiju u odnosu na myc- i bcl-2- DBKL. Postoji razlika u učestalosti bcl-2+ i myc+ u odnosu na IPI (visok IPI 47,2% i 36,1% vs nizak IPI 38,5% i 46,2%) ali bez statističke značajnosti. Uporedna analiza prognostičkog značaja dvostrukih mutacija i IPI skora ne pokazuje uticaj na preživljavanje ni kod ispitanika sa niskim rizikom, niti kod ispitanika sa visokim IPI rizikom. U grupi bcl-2+ i c-myc+ ispitanika sa niskim IPI rizikom, jednogodišnje preživljavanje bilo je 83,3%, dvogodišnje 66,7% i bez promene na kraju perioda praćenja od 7,5 godina. Kod bcl-2+ i s-myc+ ispitanika sa visokim IPI rizikom, preživljavanje posle godinu dana iznosilo je 28,6%, posle dve godine 14,3%, dok niko od obolelih iz ove grupe nije živeo duže od tri godine. Ispitanici refrakterni na terapiju imali su značajno kraće preživljavanje od ispitanika koji su imali bilo kakav odgovor na primenjeno lečenje, niko iz ove grupe ispitanika nije živeo duže od 33 meseca. Statističkom analizom nije utvrđena korelacija postojanja genskih mutacija i refrakternosti na terapiju u ovoj studiji. I u slučaju predikcije refrakternosti na terapiju dobijene vrednosti senzitivnosti (0,462) i specifičnosti (0,592) ukazuju na mali značaj prisutne bcl-2+ i c-myc+. Multivarijantnom Cox-ovom analizom kao nezavisni faktori od uticaja na preživljavanje pokazali su se: ECOG, kompletna remisija, refrakternost na terapiju, CRP i bcl-2 pozitivnost utvrđena imunohistohemijski, i to nezavisno od prisustva drugih faktora. Sumarno, rezultati ovog istraživanja su pokazali da postojanje bcl2+ i s-myc+, utvrđene FISH analizom, ni pojedinačno ni udruženo, ne pokazuju uticaj na ukupno preživljavanje, kao ni da IPI ne može biti prediktor opredeljenja za testiranje bolesnika na genski polimorfizam. Dobijeni rezultati sugerišu da postoji istovremeno više mehanizama koji uslovljavaju da jedna trećina bolesnika ima lošu prognozu i pored primenjene imunohemioterapije, zbog čega se rezultati genskih analiza bcl-2 i c-myc, moraju korelirati sa kliničkim, histomorfološkim i imunohistohemijskim informacijama. Diffuse large B cell lymphoma, as the most common type of non-Hodgkin´ s lymphomas, constitutes a heterogeneous groups of diseases with multiple genetic abnormalities. Damages of genes involved in cell cycle control and apoptosis are of particular importance. Association of bcl-2/c-myc gene rearrangement, constitutes about 60% of Double-Hit lymphoma, without a lot of data on prognostic importance. The aims of this study were to FISH analysis the impact of gene polymorphism bcl-2+ and c-myc+ on the therapeutic response as well as to investigate the possibility that the International Prognostic Index (IPI) selects patients for testing to individualized therapeutic approach. The study results showed that the genetic polymorphism of bcl-2+ and c-myc+, both individual and associated, does not significantly affect survival rate, however, it indicated poorer response to therapy compared to myc- and bcl-2- DLBCL. There is a difference in incidence of bcl-2 and c-myc+ compared to the IPI (IPI high 47.2% and 36,1% vs 38,5% IPI low and 46,2%), but without statistical significance. Comparative analysis of the prognostic significance of the double mutation and the IPI indicated no impact on survival neither in patients with a low risk, nor in patients with a high risk IPI. In the group of bcl-2+ and c-myc + of the exeminees with a low IPI risk, one-year survival was 83,3%, two-year long was 66,7% without changes at the end of follow-up period of 7,5 years. In bcl-2 + and c-myc + examinees with high IPI risk survival after one year was 28,6%, after two years of 14,3%, whereas none of the patients in this group lived longer than three years. Respondents refractory to therapy had a significantly shorter survival than those who had any kind of response to the treatment, none of these groups of patients lived longer than 33 months. Statistical analysis showed no correlations existence of genetic mutations and refractory response to the therapy in this study. And in the case of predicting refractory response to the therapy obtained values of sensitivity (0,462) and specificity (0,592), indicate the importance of a small present of bcl-2+ and c-myc+. Multivariate Cox's analysis as independent factors influence the survival proved: ECOG, complete remission, refractory to therapy, CRP and bcl-2 positivity was determined by immunohistochemistry, and irrespective of the presence of other factors. In summary, the results of this study showed that the presence of bcl-2 and c-myc+ , confirmed by FISH analysis, either individually or jointly, showed no impact on overall survival, or that the IPI could be a predictor of commitment to testing patients with the genetic polymorphism. The results suggest that there are several parallel mechanisms that require that one-third of patients have a poor prognosis despite immunochemotherapy applied, which is why the results of genetic analysis of bcl-2 and c-myc must correlate with clinical, immunohistochemical and hystomorphologic information.

Dosadašnje studije potvrđuju da adiponektin, protein koji luče adipociti, ostvaruje kardiovaskuloprotektivnu, antiaterogenu, anti- inflamatornu, antiadhezivnu, vazodilatatornu, antikataboličku i antidijabetičnu ulogu. Hipoadiponektinemija doprinosi patofiziologiji metaboličkog sindroma i koronarne bolesti, čak može biti nezavistan kardiovaskularni faktor rizika. Nivo adiponektina u serumu može biti rani marker ovih entiteta, metaboličkog sindroma i koronarne bolesti. Metod: Kliničko-laboratorijska studija preseka obuhvatila je 100 ispitanika oba pola sa metaboličkim sindromom i koronarnom bolešću. Korišćene su sledeće metode: klinički pregled, antropometrijska merenja, određivanje ukupne količne masnog tkiva osteodenzitometrijom, labora- torijska ispitivanja [koncentracija adiponektina u serumu ELISA metodom, insulina RIA metodom, glikemija OGTT-om, lipidni parametri (HOL, HDL, LDL, trigliceridi) i C-reaktivni protein], elektrokardiogramsko, ehokardiografsko merenje, analiza koronarografskih nalaza i izračunavanje aterogenih i HOMA-indeksa. Rezultati: Nivo adiponektina je u negativnoj korelaciji sa parametrima metaboličkog sindroma (gojaznost, hipertenzija, hiperglikemija i insulinska rezistencija, dislipidemija) i koronarne bolesti (broj suženja koronarnih arterija i progresija bolesti) i u pozitivnoj korelaciji sa ejekcijonom frakcijom, dijastolnom funkcijom i HDL-holesterolom. Adiponektin može biti značajan prediktor metaboličkog sindroma i koronarne bolesti i rani reprezentativni marker miokardne ishemije i vaskularne inflamacije, a hipoadiponektinemija nezavistan kardiovaskularni faktor rizika. Zaključak: Studija, prva te vrste u Srbiji, a jedna od retkih u svetu, daće značajan doprinos izučavanju adiponektina kao ranog reprezentativnog, dijagnostičkog i prediktivnog markera kod bolesnika sa metaboličkim sindromom i koronarnom bolešću. Up to date studies are confirming that adiponectin, a cytokine produced by adipocytes, exerts cardiovascular-protective role including antiatherogenic, anti-inflammatory, anti-adherent, vasodilator, anticatabolic and antidiabetic effects. Hypoadiponectinaemia contributes to the pathophysiology of the metabolic syndrome and coronary artery disease. The level of adiponectin in serum may be seen as an independent cardiovascular risk factor. In addition, the level of circulating adiponectin may be an early marker of the conditions such as metabolic syndrome and coronary artery disease. Methods: This research represents the clinical-laboratory cross-sectional study, based on the cases of 100 patients of both sexes with metabolic syndrome and/or coronary artery disease. Following methods were used: a clinical examination, anthropometric measurements, determine the total amounts of the fatty tissue osteodensitometry; laboratory testing included concentration of adiponectin in serum utilising super-sensitive sandwich ELISA-method, insulin level measured by RIA-method, glycemia OGTT-test, lipid parameters (HOL, HDL, LDL, triglycerides) and C-reactive protein, gained by standard routine biochemical protocols. All of the examinees were subjected to electrocardiogram and ehocardiogram measurement, the analysis of graphs-coronary graphically findings and calculation of atherogenic and HOMA-index. Results: The level of adiponectin showed statisticaly significant negative correllation with the key parameters of metabolic syndrome (obesity, hypertension, hyperglycemia, dyslipidemia and insulin resistance), as well as coronary artery disease. More accurately, the level of adiponectin is decreasing exact number of coronary arteries disease and simptomatology progression. Plasma levels of adiponectin positively correlated with ejection fraction, diastolic function and HDL-cholesterol. Adiponectin may be a significant predictor of metabolic syndrome and coronary heart disease, and an early representative marker of myocardial ischemia and vascular inflammation, as well as hypoadiponectinaemia independent cardiovascular risk factor. Conclusion: This study, the first of its kind in Serbia and one of the few in the world, will significantly contribute to acknowledgement of the role of adiponectin as an early representative, diagnostic and predictive markers in patients with metabolic syndrome and coronary artery disease.

Osnovna terapija kod pacijenata sa diferentovanim karcinomom štitaste žlezde (DTC) je totalna ili skoro totalna tireoidektomija i primena radioaktivnog joda (131-I). Cilj terapije radioaktivnim 131-I je eliminacija postoperativno zaostalog tireoidnog tkiva i jodavidnih metastaza. Primena 131-I indukuje jonizaciju materije praćenu oksidativnim stresom i oslobađanjem pojedinih citokina, kao i oštećenje ćelija uz povećanje frekvence mikronukleusa i moguću indukciju apoptoze limfocita periferne krvi. Osnovni cilj ovog istraživanja je da se ispitaju celularne i biohemijske promene u perifernoj krvi pacijenata sa DTC pre i sedam dana nakon aplikacije radioaktivnog 131-I. Istraživanje je dizajnirano kao komparativna kliničko-eksperimentalna studija tokom koje su upoređivani testirani parametri u eksperimentalnoj i kontrolnoj grupi ispitanika. U kliničkom ispitivanju ukupno je učestvovalo 24 pacijenta (16 žena i 8 muškaraca), prosečne starosti 50.83±13.22 godina. Četiri do šest nedelja posle totalne tireoidektomije, i 10 dana nakon dijete siromašne jodom, pacijentima je aplikovana ablaciona doza radioktivnog natrijum jodida (131-I), i to 3.7 GBq (100 mCi) (13 pacijenata) ili 5.5 GBq (150 mCi) (11 pacijenata). Kriterijumi za uključivanje u studiju bili su: histopatološki postavljena dijagnoza papilarnog ili folikularnog karcinoma štitaste žlezde nakon totalne tireoidektomije, konzilijarno doneta odluka o aplikaciji radioaktivnog 131-I, hipotireoidno stanje pacijenta (TSH>30 mIU/L) i potpisan formular informisanog pristanka saglasno Helsinškoj deklaraciji. Kliničkim ispitivanjem nisu obuhvaćeni pacijenti mlađi od 18 godina, pacijenti sa akutnim infekcijama (do mesec dana pre aplikacije 131-I), sa ranije dijagnostifikovanim i/ili lečenim autoimunskim bolestima, ranije dijagnostifikovanim i/ili lečenim hroničnim inflamatornim bolestima i ranije dijagnostifikovanim i/ili lečenim drugim tumorima, odnosno osobe kod kojih je primenjena zračna ili hemioterapija. Sve posmatrane varijable analizirane su u odnosu na kontrolnu grupu ispitanika, sastavljenu od 24 zdrava dobrovoljca, 19 žena i 5 muškaraca prosečne starosti 46.37±12.79 godina, kod kojih ranije nisu dijagnostifikovani tumori ili hronične inflamatorne bolesti, i koji mesec dana pre uzimanje uzorka krvi nisu imali akutnu infekciju sa povišenom temperaturom, a najmanje tri meseca nisu bili izloženi dejstvu jonizujućeg zračenja ili poznatih genotoksina. The initial treatment in patients with differentiated thyroid carcinoma (DTC) includes total or near total thyroidectomy and radioactive iodine (131-I) therapy. The propose of 131-I therapy is to ablate remnant thyroid tissue and treat iodine-avid metastases. 131-I induces whole body irradiation followed by oxidative stress and the release of some cytokines, as well as the cellular damage with an increase of micronucleus frequency and potential apoptosis of peripheral blood lymphocytes. The aim of this study was to investigate the cellular and biochemical changes in the peripheral blood of DTC patients before and seven days after administration of radioactive 131-I. The investigation was designed as a comparative clinical-experimental study in which we compared tested parameters in the experimental and control group of subjects. The study population included 24 well-differentiated thyroid cancer patients (16 females and 8 males), with a mean age of 50.83±13.22 years. Four to six weeks after total thyreoidectomy and 10 days after a low iodine diet, the patients were treated with fixed nominal activities of 3.7 GBq (100 mCi)(13 patients) or 5.5 GBq (150 mCi)(11 patients) of orally administrated sodium iodide (131-I). Inclusion criteria were: histopathological confirmed diagnosis of papillary or follicular thyroid carcinoma after total thyroidectomy, consultative decision about the application of radioactive 131-I, hypothyroid condition (TSH>30 mIU/L), and written informed consent according to the Declaration of Helsinki. Patients younger than 18 years, those with acute infections (one month before the application of 131-I), and previously established and/or treated autoimmune diseases, chronic inflammatory diseases and other type of tumors, as persons who underwent the radio- or chemotherapy were not included in the study. The control group consisted of 24 healthy subjects, 19 females and 5 males, with a mean age of 46.37±12.79 who had never diagnosed tumors or chronic inflammatory diseases, had no an acute infection with а fever one month before taking the blood sample, and had not been exposed to radioactive sources or other known genotoxic agents within at least 3 months.

Povećan kardiovaskularni rizik u disfunkciji štitaste žlezde u vezi je sa poremećajima metabolizma lipida i lipoproteina, endotelijalnom disfunkcijom, metaboličkim, hormonskim, hemodinamskim promenama i poremećajima koagulacije. Subklinički hipotireoidizam (SH), karakteriše se supranormalnim nivom TSH uz normalne vrednosti tireoidnih hormona. Udrženost subkliničkog hipotireoidizma sa povećanim kardiovaskularnim rizikom još uvek nije u potpunosti razjašnjen. Cilj ispitivanja predstavlja identifikaciju parametara kod bolesnika sa SH koji mogu ukazati na povećan kardiometabolički rizik, kao i procena značaja veličine i distribucije masne mase, nivoa leptina i stepena insulinske rezistencije u identifikaciji Metaboličkog sindroma H (MSH ). Metod. Istraživanjem će biti obuhvaćeno 140 bolesnika uzrasta 18-65 godina i to 105 bolesnika sa SH i kontrolna grupa od 35 zdrava, normalno uhranjena ispitanika bez SH. Kod svih ispitanika biće sproveden program istraživanja koji uključuje: detaljnu anamnezu i fizikalni pregled, antropometriska merenja (merenje telesne mase, telesne visine, obima struka, merenje masne mase tela postupkom bioelektrične impedane analize (BIA), izračunavanje indeksa telesne mase (ITM), laboratoriska ispitivanja (kompletna krvna slika, fibrinogen, CRP, acidum urikum, glikemija našte, insulinemija, leptin, lipidni i lipoproteinski status, fT3, fT4, TSH), a procena stepena insulinske rezistencije sprovešće se primenom HOMA-IR (HOMA-IR = glikemija našte (mmol/l) h insulinemija našte (μU/ml) / 22.5). Rezultati. Od 105 bolesnika sa SH, prosečne starosti 44,15±11,23 godina, 77 bolesnika (73,3%) ima MSH. U kontrolnoj grupi od 35 ispitanika, prosečne starosti 33,80±10,60 godina, samo 3 ispitanika (8,6%) ima MSH. Procenat prosečne veličine masne mase tela (%BFT) (T test=8,594, p

Hypothyroidism requires thyroxine replacement, regardlesss thyroidectomy was performed or not. The goal of this research was to determine how different groups of drugs – ACE inhibitors, selective beta blockators, Ca antagonists, nitrates, statins, or different combinations of these drugs affect TSH level at the patients on the thyroxine replacement therapy after total thyroidectomy. Research took place in 2012 and was performed on the outpatients that check their chormones at Department of Nuclear Medicine in Clinical Center Kragujevac. 247 patients were divided into groups depending on which drugs they had been prescribed. The control group involved patients taking just thyroxine without other medication. TSH level of patients in control group was compared with TSH level of patients in groups taking other drugs. Our study showed that patients that use selective beta bloskators have significantly higher level of TSH than patients that don’t take these drugs. TSH level in the grops of patients using all other drugs did not differ from the control group.

Sprovedeno je randomizovano eksperimentalno kliničko prospektivno istraživanje, u dve paralelne grupe ispitanika koji boluju od dijabetes melitusa tip 2 i kod kojih je postavljena dijagnoza distalne simetrične dijabetesne senzomotorne polineuropatije (DSMP) u cilju da se ispita i uporedi efekat fizikalnih procedura i tretmana alfalipoičnom kiselinom. U studiju su bile uključene dve grupe od po 30 pacijenata obolelih od dijabetes melitusa tip 2, kod kojih je na osnovu kliničkih simptoma i znakova, kao i parametara elektromioneurografskog (EMNG) nalaza postavljena dijagnoza DSMP. Prva grupa (grupa A) ispitanika je tretirana fizikalnom terapijom, a kod druge grupe ispitanika (grupa B) je bila primenjena alfalipoična kiselina. Protokol studije je podrazumevao da je studija sprovedena tokom tri dijagnostičko-terapijska ciklusa, svaki od njih je trajao 16 dana, a vremenski period između dva ciklusa je bio 6±1 nedelja (ukupno trajanje studije je šest meseci). U Grupi A, u ovom periodu, pacijenti su lečeni identičnom kombinacijom fizikalnih agenasa tokom 14 dana: pulsirajućim elektromagnetnim poljem (PEMP), transkutanom električnom neuralnom stimulacijom (TENS), stabilnom galvanizacijom (SG) i kineziterapijom (KTH). Prilikom primene fizikalne terapije prvo su se sprovele elektroterapijske procedure i magnetoterapija (nije bitan redosled sprovođenja terapija), a na kraju je sprovedena kineziterapija. U Grupi B je primenjena alfalipoična kiselina u skladu sa preporukom proizvođača leka i standardnom kliničkom praksom. Tokom hospitalizacije pacijenti su lečeni intravenskom aplikacijom preparata alfalipoične kiseline (600 mg u 500 ml 0,9% NaCl). Aplikacija se odvijala u uslovima zaštite od svetla, tokom 90 minuta, u vidu intravenske infuzije, svakodnevno, tokom 14 dana u vremenskom periodu od 08:00 do 10:00. Po završenoj hospitalizaciji, a tokom celog perioda studije, ovi ispitanici su nastavljali da redovno uzimaju peroralno preparat alfalipoične kiseline u dozi od 600 mg (jedna tableta dnevno, ujutru pre doručka). A randomized prospective clinical experiment was conducted over two parallel groups of patients who suffer from diabetes mellitus, type 2 and with the diagnosis of distal symmetric sensorimotor polyneuropathy (DSMP). The goal of the study is to research and compare the effects of physical procedures and of the treatment with alpha lipoic acid. The study involved two groups of 30 patients each suffering from diabetes mellitus, type 2, and with the diagnosis of DSMP set on the basis of clinical symptoms and signs, as well as on the basis of electromioneurography (EMNG) parameters. The first group (group A) of patients was treated by physical therapy, and the second group (group B) with alpha lipoic acid. According to methodology, the study was conducted during three diagnostic and therapeutic cycles, each of which lasted 16 days, while the period of time between two cycles was 6±1 weeks (total duration of the research was six months). During this period, the patients in the group A were treated with an identical combination of physical agents during 14 days: with pulsed electromagnetic field (PEMF), transcutaneous electrical nerve stimulation (TENS), stable galvanization (SG) and kinesitherapy (KTH). During the physical therapy the electro therapy procedures and magnet therapy were applied first, while the kinesitherapy was applied at the end. In the group B, alpha lipoic acid was used in compliance with the medication producer’s recommendations and the standard clinical practice. During ospitalization, the patients were treated with intravenous infusion of alpha lipoic acid (600mg in 500ml 0,9% NaCl) in the conditions protected from light, 90 minutes per day, during 14 days in the time interval from 08hrs to 10hrs. After the period of hospitalization and during the whole period of the research, the patients continued to regularly take 600mg of alpha lipoic acid perorally (one tablet per day, in the morning before breakfast). The results show that in treatment of distal symmetric diabetes polyneuropathy both therapy methods that were under research (physical therapy and use of alpha lipoic acid) have positive effects in terms of pain reduction, improvement of quality of life, improvement of electromioneurography results for peripheral nerves and strengthening of leg muscles. The therapy by combined physical procedures has better effect on pain reduction and muscle strengthening, while on the other hand the use of alpha lipoic acid has additional positive effect on biochemical parameters for regulation of glucose and lipids.

M30 M33

Trudnoća predstavlja stanje rezistencije na insulin koja u ne kih žena može da predisponira razvoj dijabetesa, koji je udružen sa povećanim rizikom i po majku i po plod. Tokom trudnoće su česti i poremećaji tiroidne funkcije, posebno autoimunska tiroidna bolest (AITB) i hipotiroidizam. Osnovni cilj istra živanja je analiza pa rametara glikoregulacije, liporegulacije i parametara funkcije štitaste žlezde tokom trudnoće. Istraživanje predstavlja kliničku, opservacionu, neinterventnu, analitičku, prospektivnu, kohortnu studiju, sprovedene u jednom centru. Osnovni kriterijum i za uključivanje pacijenata u studiju su bili: ženski pol, starost iznad 18 godina i postavljena dijagnoza vitalne i željene trudnoće u prvom trimestru. Protokol istraživanja je podrazumevao da ono bude obavljeno tokom četiri posete pa cijentkinja (u 1., 2. i 3. trimestru trudnoće, kao i četiri nedelje posle porođaja): OGTT sa 100g glukoze, sa određivanjem glikemije i insulinemije u 0, 60, 120 i 180 minutu, HbA1c, parametri funkcije štitaste žlezde (fT4, fT3, TSH, antiTG antitela, antiTPO antitela, kalcitonin), standardne laboratorijske analize, lipidogram (tHol, HDL, LDL, TAG. U dalje istraživanje su uključe ne samo pacijentkinje koje su imale sve uključujuće i ni jedan isključujući kriterijum. Na osnovu rezultata OGTT stratifikovali smo ispitanice u tri grupe: normalna tolerancija glukoze (NTG), minimalni poremećaj glikoregulacije (MPG) i gestacijski dijabetes melitus (GDM), odnosno u dve grupe : normalna tolerancija glukoze (NTG) i patološka tolerancija glukoze (PTG=MPG+G DM). Pregnancy presents a state of insulin resistance that can predipose diabetes development in some women, and is associated with increased risk for neonate and for mother. During pregnancy are often thyroid disorders, especially autoimmune thyroid disease (AITD) and hypothyreoidism. The main goal of the research was analysis of parameters glicoregulation, liporegulation and thyroid function during pregnancy. This research presents clinical, observational, noninterventional, analytic, prospective, cohort study, conducted in one center. Inclusion criteria were: female gender, older than 18 years and diagnosis of vital and desired pregnancy in the first trimester. Study protocol imply that it should be done during four visits (1st, 2nd and 3rd trimester, and 4 weeks after delivery): ОGТТ with 100 g glucose, with specifying glicemia and insulinemia in 0. , 60. , 120. and 180. minutes and HbA1c, thyroid function parameters (fТ4, fТ3, ТSH, antiТG antibodies, antiТPO аntibodies, calcitonin), standard laboratory analysis, lipids (tHol, HDL, LDL, TAG). According to OGTT results we divided patients in three groups : normal glucose tolerance (NGT), minimal disorder of glicoregulation (МDG) and gestational diabetes mellitus (GDM), respectively in two groups : normal glucose tolerance and pathologic glucose tolerance (PTG=MDG+GDM). The research included 92 pregnant women with diagnosis of vital and desired pregnancy in the first trimester, while 77 finished examination. Patients were average 30,8±4,7 (19-41) years old. It was shown that there was impact the number of risk factors on degree of glucose tolerance disorder (р=0,034), while most of patients had no risk factor (48%). From 77 patients, the 9 was with GDM, 9 was with MPG (18 with PTG). As pregnancy progress, disorder of glucose tolerance increased (in 2nd and 3rd trimester), while four weeks after delivery all were with NTG. The average insulinemia during pregnancy is the greatest in 1st and 2nd trimester in MDG group in 60. and 120. minute, in GDM group in 120. minute, during 3rd trimester greatest in 0. and 60. minute in MDG group, while in 120. and 180. minute greatest in GDM group. The average insulinemia during pregnancy is significantly great in PTG.

Background: Ishemic heart disease is mostly a consequence of atherosclerosis. Atherosclerosis, a chronic inflammatory disease, underlies the pathogenesis of coronary artery disease. The present study assessed the diagnostic and prognostic validity of inflammatory biomarkers, including high sensitive C-reactive protein (hsCRP),fibrinogen, ESR, leukocytes, serum neopterin, nitrite/nitrate (NO2 –/NO3–), inducible nitricoxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and asymmetric dimethylarginine (ADMA) and their correlation with risk factors in patients with acute coronary syndrome and stable angina pectoris. Methods: We studied 74 patients with chronic stable angina pectoris, 73 with unstable angina, 94 with acute myocardial infarction and 66 age-matched healthy volunteers (control group). Serum neopterin, ADMA, iNOS and TNF-α were determined by the commercially available enzyme linked immunosorbent assay methods and NO2 – /NO3– by the modified cadmium-reduction method. The diagnostic accuracy of markers was evaluated by the ROC curve analysis. Results: Mean serum neopterin levels were significantly higher in patients with unstable and stable angina pectoris in comparison to control subjects (p

M60 M63

M60 M63

M60 M63