<p>Uvod. Ftalati su endokrini disruptori, &scaron;iroko se koriste kao plastifikatori, rastvarači i aditivi u mnogim potro&scaron;ačkim proizvodima. Eksperimentalni podaci i humane studije sugeri&scaron;u na povezanost ftalata sa gojazno&scaron;ću i dijabetesom. Cilj. Utvrditi da li su i koji urinami metaboliti ftalata prisutni i da li postoje razlike u njihovim nivoima između bolesnika s tipom 2 &scaron;ećeme bolesti, gojaznih i kontrolne grupe zdravih osoba; da li postoji povezanost između metabolita ftalata i gojaznosti, lipida i lipoproteina seruma, glikemije, insulinemije i insulinske rezistencije.<br />Metode. Istraživanje je obuhvatilo 305 ispitanika, podeljenih u 3 grupe: gojazni (n=104), dijabetesni bolesnici tip 2 (n=101) i zdrave osobe (n=100), oba pola. U svih ispitanika su izvr&scaron;ena antropometrijska merenja (BMI i obim struka), određivanje serumskih lipida (ukupni holesterol, trigliceidi, HDL i LDL holesterol), te glikemija, insulinemija i izračunat indeks insulinske rezistencije (HOMA IRI). U jutarnjem uzorku urina meren je nivo 10 ftalatnih metabolita: mono-metil ftalat (MMP), mono-etil ftalat (MEP), mono-n-butil ftalat (MnBP), mono- benzil ftalat (MBzP), mono-cikloheksil ftalat (MCHP), mono-n-propil ftalat (MPP), mono-n-amil ftalat (MnAP), mono-izo-amil ftalat (MiAP), mono- n-oktil ftalat (MOP), mono-2-etilheksil ftalat (MEHP). U odnosu na prisustvo ftalata u urinu svaka grupa je podeljena u podgrupe na one sa prisutnim ftalatima i one bez ftalata u urinu, odnosno na podgrupe MEP pozitivne, MEP negativne, MEHP pozitivne i MEHP negativne. Rezultati. Kod polovine ispitanika registrovali smo prisustvo u urinu pojedinih metabolita ftalata. Najče&scaron;ći su bili MEHP i MEP. Najveća sličnost u nivou MEP-a i MEHP-a je bila između gojaznih i dijabetesnih ispitanika. U odnosu na antropometrij ske parametre uočena je pozitivna korelacija MEP-a sa BMI i obimom struka, a negativna korelacija MEHP-a sa BMI i obimom struka, ali su bile nesignifikantne. Samo kod MEHP pozitivnih kontrolne grupe uočena je statistički značajna pozitivna korelacija MEHP-a i obima struka. Utvrđena je statistički značajna negativna korelaciju MEP-a i HDL holesterola, a pozitivna korelacija MEP-a i triglicerida samo kod gojaznih. Samo u kontrolnoj grupi MEHP pozitivnih postojala je statistički značajna negativna korelacija sa HDL holesterolom. Postojala je pozitivna korelacija MEP-a i HOMA-IRI, a pozitivna korelacija MEHP-a sa glikemijom samo kod MEHP pozitivnih DM tip 2. Zaključak. Potvrđeno je da je kontaminacija ftalatima prisutna u na&scaron;oj populaciji, a najče&scaron;će su prisutni MEHP i MEP, ukazujući na ekspoziciju DEHP i DEP. Indirektno smo stekli uvid da povećana izloženost DEP i DEHP može doprineti nastanku izvesnih poremećaja lipida i lipoproteina, insulinskoj rezistenciji kao i razvoju gojaznosti.</p> / <p>Introduction. Phthalates are endocrine disruptors, widely used as plasticizers, solvents and additives in a wide range of consumer products. Experimental data and human studies suggest that phthalate exposure is linked with obesity and diabetes. Aim. To determine whether urinary phthalate metabolites are present, which ones are present, whether there are differences between their levels among the patients with type 2 diabetes, obesity patients and a control group of healthy individuals; whether there is a link between phthalate metabolites and obesity, lipids, serum lipoproteins, glycemia, insulinemia and insulin resistance. Methods. The research included 305 participants divided into three groups: obesity patients (n=104), type 2 diabetes patients (n=101) and healthy individuals (n=100) in both sexes. Anthropometric measurements were taken from all participants (BMI and waist circumference), as well as measurement of serum lipids (total cholesterol, triglycerides, HDL and LDL cholesterol), glycemia, insulinemia and a calculation of insulin resistance index (HOMA IRI). The levels of ten phthalate metabolites were<br />measured in a morning sample of urine: Mono-methyl phthalate (MMP), Mono-ethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), Mono-benzyl phthalate (MBzP), Mono- cyclohexyl phthalate (MCHP), Mono-n-propyl phthalate (MPP), Mono-n-amyl phthalate (MnAP), Mono-iso-amyl phthalate (MiAP), Mono-n-octyl phthalate (MOP), Mono-2- ethylhexyl phthalate (MEHP). Regarding the presence of phthalates in urine, each group was divided into subgroups, containing phthalates and or not containing phthalates, i.e. subgroups MEP positive and MEP negative, MEHP positive and MEHP negative. Results. In a half of participants, we have registered the presence of certain phthalate metabolites in urine, most often MEHP and MEP. The highest similarity in the levels of MEHP and MEP was between obesity and diabetes participants. Regarding anthropometric measurements, positive correlation has been registered between MEP and BMI and waist circumference, while negative correlation has been registered between MEHP and BMI and waist circumference, but it was insignificant. Only in MEHP positive control group, statistically significant positive correlation between MEHP and waist circumference has been registered. Statistically significant negative correlation between MEP and HDL cholesterol has been registered, while positive correlation between MEP and triglycerides has been registered only in obesity patients group. Only in MEHP positive control group statistically significant negative correlation with HDL cholesterol has been registered. There has been a positive correlation between MEP and HOMA-IRI, while positive correlation between MEHP and glycemia has been registered only in MEHP positive DM type 2. Conclusion. It has been confirmed that our population is contaminated with phthalates, most commonly MEHP and MEP, indicating exposure to DEHP and DEP. Indirectly, we have realized that an increased exposure to DEHP and DEP can contribute to the development of certain lipid and lipoprotein disorders, insulin resistance, as well as the development of obesity.</p>

<p>Bor je bilo koji četinar roda Pinus koji pripada porodici Pinaceae. U Republici Srbiji nalaze se prirodne i ve&scaron;tačke &scaron;ume crnog bora Pinus nigra Arnold. Kora bora se vekovima koristila u tradicionalnoj medicini, međutim tek u novije vreme su otkriveni i potvrđeni njeni pozitivni biolo&scaron;ki efekti u medicini. Najpoznatiji komercijalni preparat kore bora je piknogenol, standardizovani ekstrakt kore francuskog primorskog bora Pinus pinaster Aiton, koji raste duţ obale jugozapadne Francuske. Pozitivni efekti koje ispoljava piknogenol, kao &scaron;to su antioksidativno, hipoglikemijsko, hipolipidemijsko delovanje, zasnovani su na njegovom visokom sadržaju fenolnih jedinjenja. Danas, i pored saznanja da je kora bora bogata sekundarnim metabolitima ona najče&scaron;će zavr&scaron;ava kao nusproizvod drvne industrije. Ciljevi ovog rada bili su ispitivanje kvalitativnih i kvantitativnih karakteristika i biohemijskih aktivnosti ekstrakata kore crnog bora Pinus nigra sa Mokre gore i Tare, dobijenih različitim rastvaračima; upoređivanje glikemijskog i lipidnog delovanja ekstrakta kore bora Pinus nigra sa komercijalnim preparatom piknogenol; uticaj ekstrakta kore bora Pinus nigra i piknogenola na delovanje standardnih antidijabetika metformina i gliklazida; kao i uticaj na parametre oksidativnog stresa nakon izlaganja životinja toksičnoj dozi paracetamola. In vitro ispitivanja su uključivala analizu ekstrakata dobijenih različitim rastvaračima. Ukupni sadržaj fenola, tanina, flavonoida i proantocijanidna, kao i ispitivanje antioksidativne aktivnosti kroz pet različitih metoda, određivani su spektrofotometrijski. Vr&scaron;ena je analiza ekstrakata kore bora visokoefikasnom tečnom hromatografijom (HPLC). In vivo ispitivanje je rađeno na 156 albino laboratorijska pacova soja Wistar. Eksperimentalne ţivotinje su tokom 7 dana per os primale ekstrakt kore crnog bora poreklom sa Mokre gore 100 mg/kg, koji je pokazao najbolju aktivnost, piknogenol 50 mg/kg, metformin 100 mg/kg, gliklazid 10 mg/kg, kao i njihove kombinacije. Za ispitivanje uticaja primenjivanih supstanci na glikemiju ţivotinja kori&scaron;ćeni su test oralnog podno&scaron;enja glukoze i indukcija trajne hiperglikemije aloksanom. Od biohemijskih parametara u serumu je određivana koncentracija lipida, kao i parametric pokazatelji funkcije bubrega i jetre. Ex vivo ispitivanja uključivala su određivanje intenzitet lipidne peroksidacije i anktivnosti enzima antioksidativne za&scaron;tite u homogenatu jetre ispitivanih ţivotinja, nakon primene toksične doze paracetamola. HPLC analizom ekstrakata kore crnog bora utvrđeno je da ekstrakti poreklom sa Mokre gore i Tare u najvećoj meri sadrţe taksifolin, a zatim katehin, njegove derivate, kafenu kiselinu i epikatehin. PotvrĎen je visok antioksidativni kapacitet piknogenola, ali takođe i značajan antioksidativni kapacitet ekstrakata kore crnog bora, sa najboljim rezultatima kod ekstrakta poreklom sa Mokre gore. Sedmodnevni tretman ekstraktom kore bora 100 mg/kg, metforminom 100 mg/kg, gliklazidom 10 mg/kg i piknogenolom 50 mg/kg, kod ţivotinja sa aloksanski izazvanim dijabetesom, doveo je do sniženja glikemije u krvi. Uočeno je povećanje konentracije HDL holesterola i značajno sniženje serumskih triglicerida kod dijabetičnih i normoglikemičnih ţivotinja koje su primale piknogenol, ekstrakta kore bora, gliklazid i metformin u poređenju sa kontrolnom grupom ţivotinja. Zajednička primena ekstrakta kore bora i standardnih antidijabetika značajno je snizila vrednosti AST, ALP i direktni bilirubin u grupi dijabetičnih i normoglikemičnih ţivotinja u odnosu na kontrolnu grupu, čime se ukazuje na potencijalno hepatoprotektivno delovanje ekstrakta kore crnog bora. O&scaron;tećenje jetre izazvano toksičnom dozom paracetamola je potvrđeno ispitivanim parametrima, uključujući oksidativni status u homogenatu jetre i histolo&scaron;ka ispitivanja. Rezultati na&scaron;eg istraživanja su pokazali da piknogenol 50 mg/kg, kao i ekstrakt kore crnog bora 100 mg/kg značajno smanjuju nivo MDA u poređenju sa kontrolnom grupom i grupom koja je primala paracetamol. Na osnovu rezultata istraţivanja može se zaključiti da primena piknogenola i ekstrakta kore crnog bora: ublaţava poremećaj homeostaze glukoze, utiče povoljno na lipidni status, značajno potencira antihiperglikemijsko delovanje metformina i hipoglikemijski efekat gliklazida, sprečava poremećaj biohemijskih parametara pokazatelja funkcije jetre i bubrega u serumu ispitivanih životinja i ispoljava značajno in vitro antioksidativno delovanje i sprečava o&scaron;tećenje jetre laboratorijskih životinja izazvano toksičnom dozom paracetamola.</p> / <p>A pine is any conifer in the genus Pinus of the family Pinaceae. In the Republic of Serbia there are natural and artificial forests of black pine Pinus nigra Arnold. Pine bark has been used for centuries in traditional medicine, but only recently its positive biological effects has been revealed and confirmed in medicine. The most famous commercial pine bark product is Pycnogenol, a standardized extract of the French maritime pine bark (Pinus pinaster Aiton), which grows along the coast of southwestern France. The positive effects of Pycnogenol, such as antioxidant, hypoglycemic, hypolipidemic, are based on its high content of phenolic compounds. Nowdays, despite the knowledge that the pine bark is rich in secondary metabolites, it usually ends up as a by-product of the wood industry. The objectives of this dissertation were to investigate the qualitative and quantitative characteristics and biochemical activities of the black pine (Pinus nigra) extracts from Mokra gora and Tara, obtained by different solvents; comparison of glycemic and lipid action of Pinus nigra bark extract with commercial product Pycnogenol; the influence of black pine bark extract and Pycnogenol on the action of standard antidiabetics metformin and gliclazide; as well as the influence on the parameters of oxidative stress in animals exposed to the toxic dose of paracetamol. In vitro analyses included the analysis of extracts obtained with different solvents. The total phenolic, tannin, flavonoid and proanthocyanidin content, as well as the antioxidant activity tests, were determined spectrophotometrically. High-efficiency liquid chromatography (HPLC) was performed in order to determine black pine bark extract content. In vivo analyses was performed on 156 albino Wistar laboratory rats. Experimental animals received for 7 days per os: black pine bark extract obtained from Mokra gora 100 mg/kg, which showed the best activity; Pycnogenol 50 mg/kg; metformin 100 mg/kg; gliclazide 10 mg/kg; and their combinations. An oral glucose tolerance test and the aloxan-induced hyperglycaemia were used to examined the effects of the substances on experimental animals. Biochemical parameters, the lipids concentration and parameters of the kidney and liver function, were determined in animal serum. Ex vivo analyses included determination of lipid peroxidation activity and the activity of antioxidant protection enzymes in liver homogenates of the test animals, after administration of a toxic dose of paracetamol. HPLC analysis of black pine bark extracts obtained from Mokra gora and Tara showed the greatest content of taxifolin, then catechin, and its derivatives, caffeic acid and epicatechin. A high antioxidative capacity of Pycnogenol was confirmed, but also a significant antioxidant capacity of black pine bark extract, with the best results in the extract obtained from Mokra gora. Seven-day treatment in aloxan-induced diabetes animals with 100 mg/kg black pine bark extract, metformin 100 mg/kg, gliclazide 10 mg/kg and Pycnogenol 50 mg/kg led to a decrease of serum glycemic index. There was an increase in the HDL cholesterol concentration and a significant reduction in serum triglycerides in diabetic and normoglycemic animals which received Pycnogenol, black pine bark extract, gliclazide and metformin compared to the control group. Concomitant usage of the black pine bark extract and standard antidiabetics significantly reduced the levels of AST, ALP and direct bilirubin in the group of diabetic and normoglycemic animals compared to the control group, indicating the potential hepatoprotective action of the black pine bark extract. Damage to the liver caused by the toxic dose of paracetamol was confirmed by the liver homogenate oxidative status and histological examination. The results of our study have shown that Pycnogenol 50 mg/kg, as well as 100 mg/kg black pine bark extract significantly reduce the level of MDA in comparison with the control and the paracetamol treated group. Based on the results of the dissertation, it can be concluded that the use of Pycnogenol and black pine bark extract alleviate glucose homeostasis disorder; positively affects the lipid status; significantly increases the antihyperglycemic effect of metformin and the hypoglycemic effect of gliclazide; prevents impairment biochemical parameters of the liver and kidney function in the serum of the experimental animals; significantly exhibits in vitro antioxidant activity and prevents liver damage caused by toxic dose of paracetamol in experimental animals.</p>

<p>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 vr&scaron;ena na pacovima soja Wistar. Analizirana je telesna masa, glikemija, pokazatelji jetrene funkcije (AST; ALT, &gamma;-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 histolo&scaron;ki 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 poni&scaron;tava ovaj efekat i značajno povećava proliferaciju hepatocita. Hiperglikemija u aloksanskom dijabetesu nije dovela do pojačane ekspresije FXR. Izazivanje holestaze kod zdravih i dijabetičnih životinja dovelo je do porasta ekspresije FXR, koja je redukovana primenom MK i UDK. Na osnovu dobijenih rezultata može se zaključiti da sintetska 12-monoketoholna kiselina pokazuje slična hipoglikemijska, hepatoprotektivna i antioksidativna dejstva kao i prirodna ursodeoksiholna kiselina.</p> / <p>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, &gamma;-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 and diabetes model, the proliferation of hepatocytes was significantly reduced, while the use of MC and UDC reversed this effect and significantly increased the proliferation of hepatocytes. Hyperglycemia in alloxan-induced diabetes did not lead to overexpression of FXR. Induction of cholestasis in healthy and diabetic animals resulted in an increase in the expression of FXR, which is reduced by using the MK and the UDC. Based on these results we can conclude that a synthetic 12-monoketocholic acid shows similar hypoglycemic, hepatoprotective and antioxidant effects as natural ursodeoxycholic acid.</p>

<p>Cilj ovog istraživanja je da se ispita uticaj centralne debljine makularne regije (CMT) i prisustva subretinalne tečnosti na vidnu o&scaron;trinu (VA) kod pacijenata obolelih od dijabetesnog makularnog edema, kao i uticaj očuvanosti kontinuiteta spoja spolja&scaron;njeg i unutra&scaron;njeg segmenta fotoreceptora (IS/OS &ndash; kompleks) i spolja&scaron;nje granične membrane (ELM) kao prognostičkih faktora u pobolj&scaron;anju vidne o&scaron;trine nakon primenjene terapije kod pacijenata obolelih od dijabetesnog makularnog edema (DME). Materijal i metode: u ovu retrospektivno prospektivnu kliničku studiju nasumično je uključeno 100 pacijenata koji su podeljeni u dve grupe. Grupu A &ndash; prospektivni deo studije je činilo 50 pacijenata (50 očiju) kod kojih je dijagnostikovan dijabetesni makularni edem i kod kojih je inidikovana primena terapije, laserftotkogaulacije i/ili anti-VEGF terapije (bevacizumab). Grupu B &ndash; retrospektivnu grupu je činilo 50 pacijenata (58 očiju) koji su prethodno lečeni od dijabetesnog makularnog edema primenom laserfotokoagulacije i/ili anti-VEGF terapije (bevacizumab). Nakon kompletnog oftalmolo&scaron;kog pregleda koji se sastojao od određivanja vidne o&scaron;trine (optotipima po Snellenu), biomikroskopije, merenja intraokularnog pritiska i pregleda očnog dna &ndash; fundusa primenom panfundoskopa izvr&scaron;ena je optička koherentna tomografija u svih pacijenata (primenom aparata Stratus&reg; OCT, Carl Zeiss, Meditec i Copercnicus&reg; Optopol). Analiza OCT snimka, je obuhvatila određivanje centralne debljine makule (CMT), prisustva subretinalne tečnosti kao i procenu stanja očuvanosti kontinuiteta spoja spolja&scaron;enjeg i unutra&scaron;njeg segmenta fotoreceptora (IS/OS kompleks) i očuvanost kontinuiteta spolja&scaron;nje granične membrane (ELM). CMT je izračunat primenom softvera OCT aparata i izražen kao srednja vrednost za svih 9 ETDRS polja. Prisutvno subretinalne tečnosti je klasifikovano kao pozitivno ukoliko je identifikovano makar u jednom preseku OCT tomograma .Očuvanost kontinuiteta IS/OS kompleksa i ELM je analizirana u svakom pojedinačnom snimku i podeljena u 3 kategorije. Prva &ndash; ukoliko je očuvano u svim presecima, druga &ndash; ukoliko je očuvano samo u pojedinim presecima i treća &ndash; ukoliko se IS/OS kompleks i ELM nisu mogli identifikovati na nalazu OCT tomograma. Rezultati ukazuju da prisustvo subretinalne tečnosti pre primenjene terapije nema statistički značajnog uticaja na pobolj&scaron;anje vidne o&scaron;trine nakon primenjene terapije u pacijenata grupe A (pA=0,915), a statistička značajnost nije potvrđena ni kod pacijenata koji su prethodno tretirani od DME &ndash; grupa B (pB=0,772). Srednja vrednosti CMT i VA u pacijaneta grupe A iznosila je 474&mu;m&plusmn;140,67&mu;m odnosno 0.25&plusmn;0.20. Nakon primenjene terapije srednja vrednost vidnih o&scaron;trina iznosila je 0.41&plusmn;0.25, dok su vrednosti srednje vrednosti CMT iznosile 343.68&mu;m&plusmn;99.03&mu;m. Potvrđeno je statistički značajno pobolj&scaron;anje vidne o&scaron;trine nakon primenjene terapije (pVA=0,0001) i statistički značajno smanjenje centralne debljine makule (pCMT=0,0001). Korelacija VA sa vrednostima CMT pre primenjene terapije pokazuje statističku značajnost sa negativnom korelacijom (r=-0,391; p=0,005) dok se nakon primenjene terapije ne uočava statistički značajna korelacija (r=-0,047; p=0,746). Analizom vrednosti CMT pre primenjene terapije sa vrednostima VA nakon terapije se uočava statistički značajna negativna korelacija, odnosno veće vrednosti CMT pre primenjene terapije ograničavaju pobolj&scaron;anje vidne o&scaron;trine nakon primenjene terapije (r=-0,393; p=0,005). Evaluacija OCT tomograma, pre primenjene terapije, u pacijenata grupe A utvrđen je u potpunosti očuvan kontinuitet IS/OS kompleksa i ELM u svim presecima u 23 odnosno 27 očiju, u pojedinim presecima u 18 odnosno 16 očiju, i nije mogao biti identifikovan u 9 odnosno 7 očiju. U pacijenata grupe A nakon primenjene terapije uočava se statistički značajno pobolj&scaron;anje vrednosti VA u zavisnosti od očuvanosti kontinuiteta IS/OS kompleksa (F=5,550, p=0,007) i ELM (F=5,428, p=0,008). Univarijantna odnosno multivarjiantna analiza podataka za granične vrednosti vidnih o&scaron;trina od 0,1 i koraka pobolj&scaron;anja od 0,1 ukazuje na statističku značajnost prediktora IS/OS kompleksa (p=0,012 i p=0,032) i ELM (p=0,003 i p=0,018) u pobolj&scaron;anju vrednosti vidnih o&scaron;trina nakon primenjene terapije. Pacijenti sa očuvanim kontinuitetom IS/OS kompelsa u svim presecima imaju 9,5 puta (OR=9,500 ) veću &scaron;ansu za pobolj&scaron;anje VA nakon primenjene terapije u odnosu na pacijente gde kontinuitet IS/OS kompleksa nije uočljiv. Pacijenti sa očuvanim kontinuitetom IS/OS kompleksa u pojedinim presecima imaju 7 puta veću &scaron;ansu (OR=7,000) za pobolj&scaron;anje vidne o&scaron;trine nakon terapije u poređenju sa onima kod kojih IS/OS nije uočljiv. Pacijenti sa očuvanim kontinuitetom ELM u svim presecima imaju 34,5 puta (OR=34,500 ) veću &scaron;ansu za pobolj&scaron;anje vidne o&scaron;trine u odnosu na pacijente gde ELM nije uočljiv. Pacijenti sa očuvanim kontinuitetom ELM u pojedinim presecima imaju 18 puta veću &scaron;ansu (OR=18,000) za pobolj&scaron;anje VA nakon terapije u odnosu na one kod kojih ELM nije uočljiv. Pored statistički značajnog uticaja očuvanosti kontinuiteta IS/OS kompleksa i ELM na pobolj&scaron;anje vrednosti vidnih o&scaron;trina nakon primenjene terapije, uočava se i pozitvna korelacija između vidnih o&scaron;trina pre i nakon terapije (r=0,869; p=0,0001). U pacijenata grupe B srednja vrednost CMT odnosno VA iznosila je 253,72&mu;m&plusmn;75,27&mu;m odnosno 0,68&plusmn;0,29. Postoji statistički značajna razlika u vrednostima VA u odnosu na očuvanost kontinuiteta IS/OS kompleksa (F=107,913, p=0,0001) i ELM (F=25,619, p=0,0001). Poređenjem vrednosti parametara za obe posmatrane grupe uočava se statistički značajna razlika u vrednostima CMT koje su bile manje u grupi B (t=5,355, p=0,0001) i srednjim vrednostima VA ( t=5,137, p=0,0001) koje su bile veće u grupi B. Analizom očuvanosti kontinuiteta IS/OS kompleksa (&chi;2=0,119, p=0,730) i ELM (&chi;2=2,957, p=0,085) ne uočava se statistički značajna razlika. Zaključak: Odnos vidnih o&scaron;trina sa centralnom debljinom makule prikazuje različite vrednosti vidnih o&scaron;trina za iste vrednosti centralne debljine makule. Značajan uticaj na vidnu o&scaron;trinu pacijenata obolelih od DME ima očuvanost integriteta spolja&scaron;nje granične membrane (ELM) i spoja unutra&scaron;njeg i spolja&scaron;njeg segmenta fotoreceptora (IS/OS kompleks) evaluiranih na osnovu OCT snimka &ndash; tomograma. Očuvanost integriteta ELM i IS/OS kompleksa u svim presecima na OCT tomogramu pre primenjene terapije u pacijenta sa DME se mogu smatrati pozitivnim prognostičkim faktorom u pobolj&scaron;anju vidne o&scaron;trine nakon primenjene terapije. U pacijenata kod kojih je kontinuitet ELM i IS/OS kompleksa očuvan u svim pravcima vrednost CMT pre primenjene terapije nema uticaj na pobolj&scaron;anje vidne funkcije nakon terapije. Integritet IS/OS kompleksa i ELM ima pozitivnu korelaciju sa vidnom o&scaron;trinom bez obzira na vrstu primenjene terapije, anti-VEGF odnosno laserfotokoagulacije. Prisustvo subretinalne tečnosti ne utiče na vidnu o&scaron;trinu pacijenata obolelih od DME. Vrednosti VA pre terapije utiču na pobolj&scaron;anje vidne o&scaron;trine nakon terapije.</p> / <p>The aim of this study was to investigate the influence of the central macular thickness (CMT) and the presence of sub retinal fluid on visual acuity (VA) in patients with diabetic macular edema, as well as the impact of preservation and continuity of the photoreceptor inner/outer segment junction (IS / OS - complex ) and external limiting membrane (ELM) as a prognostic factor in improving visual acuity after the applied therapy in patients with diabetic macular edema (DME). Materials and Methods: this retrospective - prospective randomized clinical study included 100 patients who were divided into two groups. Group A - a prospective part of the study, consisted of 50 patients (50 eyes), with the diagnosis of diabetic macular edema in which laser photocoagulation and / or anti-VEGF therapy (bevacizumab) was indicated. Group B - retrospective group, consisted of 50 patients (58 eyes), who were previously treated for diabetic macular edema either with laser photocoagulation and / or anti-VEGF therapy (bevacizumab). After complete ophthalmologic examination, which consisted of the determination of visual acuity (measured with Snellen charts), biomicroscopy, intraocular pressure measurement and inspection of the fundus, optical coherence tomography was performed in all patients (using the Stratus&reg; OCT, Carl Zeiss Meditec and Copercnicus&reg; Optopol). Analysis of OCT image, included the determination of the central macular thickness (CMT), presence of sub retinal fluid, as well as an assessment of the preservation of the continuity of the photoreceptor inner/outer segment junction (IS/OS - complex) and external limiting membrane (ELM). CMT is calculated using software of the OCT apparatus and expressed as the mean value for all 9 ETDRS fields. Presence of sub retinal fluid is classified as positive if it is identified in at least one cross-section of OCT tomogram. Preserved continuity of IS / OS complex and ELM is analyzed in each individual OCT cross-section image and divided into 3 categories. First - if it is preserved in all cross sections images, the second - if it is preserved only in certain sections and the third - if the IS / OS complex and ELM were not able to identify in OCT tomograms. The results indicate that the presence of sub retinal fluid before the applied therapy has no statistically significant effect on improving visual acuity after the applied therapy in patients of group A (pA = 0.915), and statistical significance was not also confirmed in any of the patients who were previously treated by DME - Group B (pB = 0.772). Mean CMT and VA values of patients in group A was 474&mu;m &plusmn; 140,67&mu;m and 0.25 &plusmn; 0.20. After receiving therapy mean visual acuity was 0.41 &plusmn; 0.25, while the value of the mean CMT was 343.68&mu;m&plusmn; 99.03&mu;m. Significant improvement in visual acuity was achieved after the treatment in group A (pVA = 0.0001) together with statistically significant reduction in central macular thickness (pCMT = 0.0001). Correlation of VA with the values of CMT before applied therapy shows statistically significant negative correlation (r = -0.391; p = 0.005), while after the applied therapy statistical significance was not observed (r = -0.047; p = 0.746). Analyzing the values of CMT before the applied therapy with the values of VA after the treatment statistically significant negative correlation was observed, higher values of CMT before the applied therapy restrict visual acuity improvement after the applied therapy (r = -0.393; p = 0.005). Analyzing OCT tomograms in the patients in group A, before the applied therapy, fully preserved continuity of IS/OS complex and ELM in all the sections was found in 23 and 27 of the eyes, in certain sections in 18 and 16 of the eyes, and could not be identified in 9 and 7 eyes. Statistically significant improvement in VA, after the applied therapy, in patients in group A is observed, depending on the preservation of continuity of IS/OS complex (F = 5.550, p = 0.007) and ELM (F = 5.428, p = 0.008). Univariate and multivariate analysis with cut off VA value of 0.1 and step improvements of 0.1 points to statistically significant predictor of IS/OS complex (p = 0.012 and p = 0.032) and ELM (p = 0.003 and p = 0.018) in improving the VA after the applied therapy. Patients with preserved continuity of IS/OS complex in all sections are 9.5 times (OR = 9.500) more likely to improve the VA after receiving therapy compared to patients where continuity of IS/OS complex is not noticeable. Patients with preserved continuity of IS/OS complex in the some sections are 7 times more likely (OR = 7.000) for the improvement of visual acuity after treatment compared to those in which the IS/OS is not detectable. Patients with preserved continuity of ELM in all sections are 34.5 times (OR = 34,500) a greater chance to improve visual acuity compared to patients where ELM is not apparent. Patients with preserved continuity of ELM in the some sections are 18 times more likely (OR = 18,000) to improve the VA after treatment compared to those in which the ELM is not apparent. In addition to statistically significant impact of preservation of continuity of IS/OS complex and ELM for VA improvement after the treatment, statistically significant positive correlation between visual acuity before and after treatment (r = 0.869; p = 0.0001) was observed. In Group B patients, the mean CMT and VA value was 253,72&mu;m&plusmn;75,268&mu;m and 0.68 &plusmn; 0.29. There is a statistically significant difference in the VA values compared to the preservation of continuity of IS/OS complex (F = 107.913, p = 0.0001) and ELM (F = 25.619, p = 0.0001). Comparing the values of parameters for both groups, statistically significant difference in CMT values and mean VA was observed. CMT values were lower (t = 5.355, p = 0.0001) while VA values were higher (t = 5.137, p = 0.0001), in group B. The analysis of preservation of continuity of IS/OS complex (&chi;2 = 0.119, p = 0.730) and ELM (&chi;2 = 2.957, p = 0.085) did not show a statistically significant difference. Conclusion: The relationship of visual acuity with central macular thickness shows the different levels of visual acuity for the same value of the central macular thickness. A significant impact on VA in patients with DME has maintained integrity of the external limiting membrane (ELM) and the photoreceptors inner/outer segments junction (IS/OS complex) evaluated on the basis of OCT - tomograms. Preservation of the integrity of the ELM and IS/OS complex in all sections of the OCT tomogram before applied therapy in patients with DME can be considered a positive prognostic factor in improving visual acuity after receiving therapy. In patients with preserved continuity of ELM and IS/OS complex in all sections before applied therapy the CMT value has no effect on the improvement of visual function after treatment. Regardless of the type of applied therapy, anti-VEGF and/or laser photocoagulation preserved integrity of IS/OS complex and ELM has a positive correlation with visual acuity. The presence of sub retinal fluid does not affect the visual acuity in patients with DME. The values of VA before treatment influence the improvement of visual acuity after treatment.</p>

<p>Uvod: Dijabetes melitus (DM) je oboljenje koje poprima karakteristike globalne epidemije. Sve ţe&scaron;&scaron;e oboljevaju pacijenti mlaŤeg ţivotnog doba. Simptomi DM tip 2 su blagi, ţesto neprimetni, te se oboljenje otkriva kada se ve&scaron; manifestuju komplikacije. Dijabetesna nefropatija (DN) je jedna od mnogobrojnih komplikacija dijabetes melitusa tip 2, koja se zavr&scaron;ava terminalnom bubreţnom insuficijencijom. DN se ţesto neblagovremeno dijagnostikuje, zbog ţega se kasno zapoţinje leţenje. Rano otkrivanje DN od kljuţnog je znaţaja, jer omogu&scaron;ava primenu terapijskih postupaka usmerenih na oţuvanje preostalih zdravih nefrona i prevenciju terminalne bubreţne slabosti. Cilj: Prikazati poreme&scaron;aj difuzije molekula vode unutar bubrega kod DN, kori&scaron;&scaron;enjem mapa prividnog koeficijenta difuzije, kvantifikacijom vrednosti prividnog koeficijenta difuzije (ADC) i frakcione anizotropije (FA). Materijal i metode: U prospektivnu studiju bilo je ukljuţeno 10 zdravih dobrovoljaca i 91 pacijent oboleo od DM tip 2. Pacijenti oboleli od DM tip 2 podeljeni su u ţetiri grupe na osnovu vrednosti procenjene jaţine glomerularne filtracije (JGF) (grupe: I JGF &ge; 90, II 89-60, III 59-30, IV &le; 29 ml/min/1,73m&sup2;). Svim ispitanicima uraŤen je MR pregled bubrega, uz primenu DWI (b=0 i b=400 s/mm&sup2;) i DTI (b=1000 s/mm&sup2;) sekvence, na aparatu jaţine 1.5T. ADC i FA vrednosti raţunate su u &scaron;est regija od interasa, po tri u korteksu i meduli svakog bubrega. Dobijene vrednosti komparirane su sa laboratorijskim parametrima bubreţne funkcije (urea, kreatinin, mokra&scaron;na kiselina) i procenjenom JGF. Rezultati: Ne postoje statistiţki znaţajne razlike ADC i FA vrednosti parenhima, korteksa i medule levog i desnog bubrega kod zdravih dobrovoljaca i DM pacijenata. Kod DM pacijenata ADC je ve&scaron;a u korteksu nego u meduli (p=0,00), a FA vrednost je ve&scaron;a u meduli nego u korteksu (p=0,284). Urea, kreatinin i cistatin C imaju negativnu korelaciju sa ADC korteksa, medule i parenhima (p&lt;0,05), a JGF ima pozitivnu korelaciju sa ADC korteksa, medule i parenhima, kao i sa FA medule (p&lt;0,05) kod DM pacijenata. Na osnovu Post hoc testa za ADC, kod DM pacijenata postoje razlike izmeŤu I i IV grupe, izmeŤu II i IV grupe i III i IV grupe (p&le;0,05). IzmeŤu godina ţivota, teţine, BMI, JGF, HbA1c, uree i &Scaron;UK-a, postoji razlika DM pacijenata i zdravih dobrovoljaca (p&lt;0,05). Niţa je vrednost FA medule DM pacijenata u odnosu na zdrave dobrovoljce (p&lt;0,05). Postoji razlika ADC korteksa, medule i parenhima izmeŤu zdravih dobrovoljaca i DM pacijenata IV grupe, kao izmeŤu DM pacijenata I i II grupe u odnosu na IV grupu. TakoŤe postoji razlika izmeŤu FA medule zdravih dobrovoljaca i DM pacijenata I i IV grupe (p&lt;0,05). Regresiona analiza pokazala je uticaj kreatinina na ADC desnog bubrega i ADC oba bubrega, dok procenjena JGF i cistatin C imaju uticaj na ADC desnog i levog bubrega, ADC oba bubrega i FA levog bubrega (p&lt;0,05). Traktografija je prikazala naru&scaron;enu arhitektoniku kod pacijenata sa o&scaron;te&scaron;enom bubreţnom funkcijom. Zakljuţak: Postoji korelacija laboratorijskih parametara bubreţne funkcije i procenjene JGF sa ADC i FA vrednostima bubrega, &scaron;to ukazuje na ulogu funkcionalnog magnetno rezonantnog imidţinga u dijagnostici dijabetesne nefropatije. Neophodna su dalja istraţivanja koja &scaron;e doprineti standardizaciji MR protokola i potvrdi znaţaja MR biomarkera u dijagnostici DN. Na osnovu na&scaron;ih rezultata vrednost FA medule osetljiviji je parametar od ADC vrednosti u otkrivanju ranog o&scaron;te&scaron;enja bubrega u sklopu dijabetes melitusa.</p> / <p>Introduction: Diabetes mellitus (DM) is a disease that takes on the characteristics of a global epidemic. Patients of younger age are more and more commonly affected. Symptoms of type 2 DM are mild, often imperceptible, and therefore the disease is usually detected when complications are already manifested. Diabetic nephropathy (DN) is one of the many complications of type 2 diabetes mellitus that leads to terminal renal failure. Diagnosis of DN is often late, causing the delay of the treatmen. Early detection of DN is crucial because it allows the application of therapeutic procedures aimed at preserving the remaining healthy nephrons and preventing terminal renal failure. Objective: To investigate a diffusion of water molecule within a kidney in DN using apparent diffusion coefficient maps, by quantification of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values in diabetic patients with DM type 2. Material and methods: The prospective study comprised 10 healthy volunteers and 91 DM type 2 patients. DM patients were divided into four groups based on the values of the estimated glomerular filtration (eGFR) (groups: I eGFR &ge; 90, II 89-60, III 59-30, IV &le; 29 ml/min/1.73m&sup2;). All subjects were scanned by 1.5T MR using DWI (b=0 and b=400 s/mm&sup2;) and DTI (b=1000 s/mm&sup2;) sequences. ADC and FA values were calculated in six regions of interest, three in cortex and three in medulla of each kidney. Obtaned values were compared to laboratory parameters of renal function (urea, creatinine, uric acid) and eGFR. Results: There were no statistically significant differences between ADC and FA values of parenchyma, cortex and medulla of the left and the right kidney in healthy volunteers and DM patients. In DM patients, the ADC value was higher in the cortex than in the medulla (p=0.00) and the FA value was higher in the medulla than in the cortex (p=0.284). The negative correlation was found between urea, creatinine and cystatin C with ADC cortex, medulla and parenchyma (p&lt;0.05), and the eGFR was positively correlated with ADC cortex, medulla and parenchyma, and with FA medulla (p&lt;0.05) in DM patients. Based on the Post hoc test for ADC, in DM patients there were differences between I and IV group, between II and IV group, III and IV group (p&le;0,05). Regarding age, weight, BMI, GFR, HbA1c, urea, and glucose in the serum, there was a difference between DM patients and healthy volunteers (p&lt;0.05). The FA of medulla in DM patients was lower than of healthy volunteers (p&lt;0.05). There were differences in ADC of cortex, medulla, and parenchyma between healthy volunteers and DM patients of IV group, as well as between DM patients of I and II group compared to IV group. There were differences of medulla FA values between healthy volunteers and group I, accompanied by healthy and IV group of DM patients (p&lt;0.05). Regression analysis showed the influence of creatinine on ADC of right kidney and ADC of both kidneys, while eGFR and cystatin C have an effect on ADC of right and left kidney, ADC of both kidneys and FA of left kidney (p&lt;0.05). The tractography showed the disturbed architectonics in patients with impaired renal function. Conclusion: There is correlation of laboratory parameters of renal function and eGFR with ADC and FA values of the kidney, indicating the role of functional magnetic resonance imaging in the diagnosis of DN. Further research that will contribute to standardizing the MR protocol and confirming the importance of MRI biomarker in the diagnosis of DN are needed. Based on our results, the values of medulla FA is more sensitive parameter than the ADC value in detecting early kidney damage in the context of diabetes mellitus.</p>

<p>Gliklazid je jedan od najče&scaron;će kori&scaron;ćenih lekova u terapiji dijabetes melitusa tip 2. U poslednje vreme, utvrđeno je da gliklazid ispoljava i druge pozitivne farmakolo&scaron;ke efekte kao &scaron;to su imunomodulatorni i anti-koagulacioni efekti, ukazujući na njegovu potencijalnu primenu u terapiji dijabetes melitusa tip 1. Gliklazid se odlikuje varijabilnim stepenom apsorpcije nakon peroralne primene i iz tog razloga pretpostavlja se da bi tehnike njegove ciljane isporuke, kao &scaron;to je mikroinkapsulacija, mogle da dovedu do pobolj&scaron;anja njegove apsorpcije i njegove potencijalne primene u terapiji T1DM. Pokazano je da različite žučne kiseline, uključujući i holnu, imaju stabilizacione efekte u domenu primene mikrovezikula i kontrolisanog osobađanja lekova, te je moguće da bi njihov dodatak u mikrovezikularnu formulaciju gliklazida mogao dodatno da pobolj&scaron;a oslobađanje gliklazida, njegovu apsorpciju i antidijabetičke efekte. S tim u vezi, cilj ovog istraživanja je da se ispita hipoglikemijski efekat gliklazida primenjenog u obliku alginatnih mikrovezikula, sa ili bez dodatka holne kiseline na T1DM modelu pacova. Trideset &scaron;est pacova obolelih od T1DM indukovanog aloksanom i odgovarajuće zdrave kontrolne životinje su nasumično raspoređene u &scaron;est grupa (n=6) i tretirane jednokratnom dozom fiziolo&scaron;kog rastvora, suspenzijom gliklazida, gliklazidom u obliku alginatnih mikrovezikula, samo holnom kiselinom, i mikrovezikulama gliklazida sa ili baz dodatka holne kiseline. Uzorkovana je krv tokom 10 h nakon unete doze i merena je koncentracija glukoze u krvi I koncentracija gliklazida u serumu kori&scaron;ćenjem HPLC metode. Mikrovezikule gliklazida su ispoljile hipo-glikemijski efekat kod pacova obolelih od dijabetesa, uprkos njegovim smanjenim koncentracijama u serumu, dok je dodatak holne kiseline u mikrovezikularnu formulaciju smanjio hipoglikemijski efekat gliklazida. Ovo potvrđuje izostanak sinergističkog efekta između gliklazida i holne kiseline. Takođe, ni proces mikroinkapsulacije niti dodatak holne kiseline nisu doprineli pobolj&scaron;anju apsorpcije gliklazida, &scaron;to ukazuje na činjenicu da su njegovi hipoglikemijski efekti nezavisni od njegove apsorpcije i koncentracije u serumu. Stoga se može pretpostaviti da su hipoglikemijski efekti gliklazida pre pod uticajem crevno-metaboličke aktivacije nego ciljanog oslobađanja u digestivnom traktu sistemske apsorpcije. Mikrovezikule gliklazida ispoljavaju hipoglikemijski efekat kod pacova obolelih od T1DM nezavisno od insulina, te mogu imati potencijalnu primenu u terapiji T1DM. Ovaj rad su podržali: HORIZON 2020 MEDLEM projekat broj 690876; Projekat Sekretarijata naučnog i tehnolo&scaron;kog razvoja Vojvodine broj . 114-451-2072-/2016-02; Projekat Ministarstva obrazovanja, nauke i tehnolo&scaron;kog razvoja Republike Srbije broja 41012.</p> / <p><!--[if gte mso 9]><xml> <o:DocumentProperties> <o:Author>mladen</o:Author> <o:Version>16.00</o:Version> </o:DocumentProperties> <o:OfficeDocumentSettings> <o:AllowPNG/> </o:OfficeDocumentSettings></xml><![endif]--><!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:TrackMoves/> <w:TrackFormatting/> <w:PunctuationKerning/> <w:ValidateAgainstSchemas/> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:DoNotPromoteQF/> <w:LidThemeOther>EN-US</w:LidThemeOther> <w:LidThemeAsian>X-NONE</w:LidThemeAsian> <w:LidThemeComplexScript>X-NONE</w:LidThemeComplexScript> 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<p>Prema podacima iz 2011 godine, u Srbiji je približno 630 000 ljudi (8,6%) obolelo od dijabetes melitus-a, a procenjuje se da će taj broj porasti na 730 000 (10,2%) do 2030 godine. Preko 90% obolelih ima tip 2 dijabetes melitus (T2DM). Prva linija medikamentne terapije predstavljaju bigvanidi čiji je najznačajniji predstavnik metformin. Prema literaturnim podacima, u oko 10-30% sluĉajeva, kontinuirana upotreba metformina ima za posledicu smanjenu intestinalnu apsorpciju vitamina B12. Tačan patofiziolo&scaron;ki mehanizam koji dovodi do metforminom indukovane malapsorpcije vitamina B12 nije u potpunosti ispitan i poznat i postoji nekoliko aktuelnih teorija s ciljem obja&scaron;njenja ovog kompleksnog problema. Cilj rada je bio utvrđivanje nivoa, dinamike, trenda i učestalosti promena vitamina B12, holotranskobalamina (B12 aktiv), homocisteina i folne kiseline tokom kontinuirane primene metformina tokom godinu dana. Studija praćenja je sprovedena u Centru za laboratorijsku medicinu a u saradnji sa Klinikom za endokrinologiju, dijabetes i bolesti metabolizma, Kliničkog centra Vojvodine. Ovom studijom je obuhvaćeno 50 ispitanika obolelih od T2DM a u momentu uvođenja metformina. Svim ispitanicima je određivana koncentracija vitamina B12, B12 aktiva, homocisteina i folne kiseline, u momentu uvođenja terapije kao i nakon 4, 8 i 12 meseci primene metformina. Za dvanaest meseci kontinuirane primene metformina, utvrđen je kontinuirani pad i redukcija vrednosti ukupnog vitamina B12 za 25.29 %, odnosno vrednosti B12 aktiva za 23.26 %. U toku ispitivanja, utvrđen je kontinuirani trend porasta vrednosti homocisteina u krvi, s statistički značajnim porastom vrednosti homocisteina nakon osam meseci primene metformina. Po&scaron;av&scaron;i od predpostavki da metformin istovremeno blokira apsorpciju vitamina B12 u gastrointestinalnom traktu kao i raspoloživost iz postojećih, tkivnih rezervi, zatečene količine ovog vitamina u ciljnim ćelijama se postepeno redukuju i tro&scaron;e, rezultujući krajnjem snižavanju nivoa metabolički aktivnih oblika kobalamina, te posledičnoj akumulaciji homocisteina kako u ćelijskom, tako i u vanćelijskom prostoru. Na osnovu dobijenih rezultata ispitivanja može se predložiti opservacija nivoa ukupnog vitamina B12 i homocisteina u krvi pre uvođenja metformina u terapiju tipa 2 dijabetes melitusa kao i dvanaest meseci nakon toga. Na osnovu nivoa jednogodi&scaron;njeg pada koncentracija ukupnog vitamina B12, porasta koncentracija homocisteina, kao i drugih kliničkih i laboratorijskih parametara, može se razmatrati opcija uvođenja supstitucione terapije vitaminom B12 ili dalja opservacija nivoa vitamin B12 u krvi i ćelijskom prostoru.</p> / <p>According to data from 2011, in Serbia, approximately 630.000 people (8.6%) were diagnosed with diabetes mellitus, and it is estimated that this number will increase to 730.000 (10.2%) by 2030. Over 90% are type 2 diabetes mellitus (T2DM) patients. The first line of medication therapy is metformin. According to the literature data, in about 10-30% of cases, continuous use of metformin causes impared intestinal absorption of vitamin B12. The exact pathophysiological mechanism leading to metformin induced malabsorption of vitamin B12 has not been fully known, and there are several current theories to explain this complex problem. The aim of this study was to determine the level, dynamics, trend and frequency of changes in blood levels of total vitamin B12, holotranscobalamin (B12 active), homocysteine and folic acid during continuous application of metformin, over a year. The study was carried out at the Center of Laboratory Medicine in cooperation with the Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Vojvodina. This study included 50 T2DM patients at the time of the introduction of metformin therapy. Levels of vitamin B12, holotranscobalamin, homocysteine and folic acid are determined before and after 4, 8 and 12 months of metformin administration, to all subjects. After a year of metformin use, the level of total vitamin B12 has been reduced by 25.29%, as well as holotranskobalamin by 23.26%. During the study, a continuous elevation of homocysteine levels was determined, with statistically significant increase in homocysteine values after eight months of metformin administration. Starting from the assumption that metformin blocks the absorption of vitamin B12 in the gastrointestinal tract as well as the availability of existing tissue reserves, the amount of this vitamin in the target cells is gradually reduced, resulting in an extremely low level of metabolically active forms of this vitamin and the consequent accumulation of homocysteine in intracellular and extracellular space. On the basis of the obtained test results, it may suggest observation of the level of total vitamin B12 and homocysteine prior to the introduction of metformin in T2DM therapy and after one year thereafter. Based on the level of one-year decline of total vitamin B12 and the increase of homocysteine concentrations, as well as other clinical and laboratory parameters, substitution therapy with vitamin B12 or further monitoring of laboratory parameters of vitamin B12 metabolism may be proposed.</p>

<p>Bosiljak (Ocimum basilicum L.) pripada familiji Lamiaceae i jedna je od najrasprostranjenijih i najče&scaron;će gajenih biljaka &scaron;irom sveta. Njegova upotreba je &scaron;iroko rasprostranjena zbog bogatog sadržaja i skladnog odnosa vitamina, minerala kao i različitih fenolnih jedinjenja kao glavnih nosilaca antioksidativne aktivnosti. Poslednjih godina velika pažnja je usmerena ka fenolnim fitokomponentama kao potencijalnim promoterima zdravlja. Ciljevi ovog rada bili su ispitivanje kvalitativnih i kvantitativnih karakteristika, kao i biohemijskih aktivnosti ekstrakata bosiljka dobijenih različitim rastvaračima, kao i ispitivanje uticaja farmaceutsko-tehnolo&scaron;ke formulacije u obliku mikrovezikula ekstrakta bosiljka na glikemijski, lipidni i oksido-redukcioni status kod oglednih životinja, u odnosu na vodeni ekstrakt. In vitro ispitivanja su uključivala analizu 100 ekstrakata dobijenih različitim rastvaračima i stepenom usitnjenosti. Ukupni fenolni i flavonoidni sadržaj, kao i antioksidativna aktivnost određena je spektrofotometrijskom metodom. Takođe, kvantifikovane i kvalifikovane su fenolne komponente (fenolne kiseline i flavonoidi) primenom visokoefikasne tečne hromatografije (HPLC). In vivo ispitivanje je rađeno na 84 albino laboratorijska pacova soja Wistar. Per os su primenjivani vodeni ekstrakt bosiljka, rastvor natrijumove soli monoketoholne kiseline, njihove kombinacije, kao i ekstrakt u obliku farmaceutsko-tehnolo&scaron;ke formulacije, mikrovezikula. Posle sedmodnevnog tretmana, merene su koncentracije glukoze u krvi, a nakon žrtvovanja, u serumu su određeni parametri lipidnog statusa i antioksidativnog stresa. Ex vivo analizama procenjivani su efekti ekstrakta bosiljka na enzimske i neenzimske parametre antioksidativnog odbrambenog sistema i oksidativne modifikacije lipida. Praćen je i uticaj tretmana na akutno o&scaron;tećenje jetre usled primene paracetamola. Svi analizirani ekstrakti bosiljka su pokazali prisustvo velikog broja fenolnih jedinjenja iz klase fenolnih kiselina i flavonoida. Detektovane i kvantifikovane aktivne komponente bile su fenolne kiseline: hlorogenska, p-hidroksibenzoeva, kafena, vanilinska, ferulna, rozmarinska i cimetna, kao i apigenin, kvercetin, naringenin i rutin kao predstavnici flavonoidnih jedinjenja. Primena ekstrakta bosiljka i natrijumove soli monoketoholne kiseline, same ili u kombinaciji, a takođe i u farmaceutsko-tehnolo&scaron;koj formulaciji, pokazale su smanjenja o&scaron;tećenja tokom oksidativnog stresa, značajno antidijabetesno delovanje, povoljan uticaj na lipidni status i protektivni efekat na funkcije jetre i bubrega. Na osnovu dobijenih rezultata može se zaključiti da ekstrakt bosiljka sadrži značajnu količinu fenolnih jedinjenja odgovornih za antioksidativnu aktivnost. Vodeni ekstrakt bosiljka, sam ili u kombinaciji sa monoketoholnom kiselinom, i u obliku farmaceutsko-tehnolo&scaron;ke formulacije snižava nivo glukoze u krvi, ubrzava obnovu &beta; ćelija, ima povoljan efekat na lipidni status i ne dovodi do toksičnih promena na jetri i bubrezima kod eksperimentalnih životinja.</p> / <p>Basil (Ocimum basilicum L.) belongs to the family Lamiaceae and represents one of the most widespread and most commonly cultivated plant worldwide. Its use is widespread due to its rich content and harmonious relationship of vitamins, minerals and various phenolic compounds which are responsible for the antioxidant activity. In recent years, great attention is directed to phenolic phytocomponents as potential promoters of health. The objectives of this study were to test the qualitative and quantitative characteristics, as well as the biochemical activity of basil extracts obtained by various solvents and investigate the impact of pharmaceutical technological formulation of basil extract on glycemic, lipid and oxidation-reduction status of the aqueous extract in the experimental animals. In vitro studies have included 100 extracts obtained by various solvents and degrees of fragmentation. Total phenolic and flavonoid content, as well as antioxidant activity was determined by spectrophotometric method. Also, phenolic compounds (phenolic acids and flavonoids) were qualified and quantified using high performance liquid chromatography (HPLC). In vivo testing was performed on 84 laboratory albino Wistar rats. The aqueous extract of basil, a solution of sodium salt of monoketocholic acid, their combinations, as well as an extract in the form of the pharmaceutical technological formulation were administered per os. After seven-day-treatment, the concentrations of glucose were measured in the blood and after sacrificing of animals, the lipid and antioxidative parameters were determined in serum. Ex vivo analysis assessed the effect of the extract of basil on the parameters of enzymatic and non-enzymatic antioxidant defense system and the oxidative modification of lipids. The effect of paracetamol on acute liver injury was also monitored. All analyzed basil extracts showed the presence of the large number of phenolic compounds from the class of phenolic acids and flavonoids. Chlorogenic, p-hydroxybenzoic, caffeic, vanillic, ferulic, rosmarinic, and cinnamic acid, as well as apigenin, quercetin, naringenin and rutin were detected and quantified. The application of basil extracts and the sodium salt of monoketocholic acid, either alone or in combination, and also in pharmaceutical technological formulation of microvesicles has shown a reduction in damage during oxidative stress, then a significant antidiabetic activity, favorable effect on the lipid profile and protective effect on the liver and kidney function. Based on these results it can be concluded that basil extract contains significant amounts of phenolic compounds responsible for antioxidant activity. The aqueous extract of basil, alone or in combination with monoketocholic acid, and in the form of the pharmaceutical technological formulations lowers glucose levels in the blood, accelerates the restoration of &beta; cells, has a favorable effect on the lipid status and does not lead to toxic changes in the liver and kidneys in experimental animals.</p>

<p>Iako je dijabetes melitus (DM) tip 2 je hronično oboljenje čija se stopa značajno povećala poslednjih decenija, podaci o odnosu pacijenta prema leku i lečenju dijabetes melitusa su retki i odnose se na pojedine aspekte terapije. Glavni kamen spoticanja u lečenju dijabetesa jeste nepridržavanje pacijenata propisanim lekovima, &scaron;to otežava održavanje normalne glikoregulacije i doprinosi razvoju te&scaron;kih komplikacija koje značajno utiču na kvalitet života pacijenata sa DM. Raspolaganje tačnim podacima o upotrebi antidijabetičnim lekova, kao i uvidom u realno stanje o odnosu pacijenata prema leku u lečenju DM tipa 2, omogućava pobolj&scaron;anje farmakoterapijske prakse i kreiranje intervencije za pobolj&scaron;anje adherencije pacijenata Ciljevi ovog istraživanja bili su: 1) analiza obima potro&scaron;nje i strukture antidijabetičnih lekova na teritoriji Republike Srpske i njihovo poređenje sa upotrebom i strukturom propisivanja u okolnim zemljama kao i državama sa razvijenom farmakoterapijskom praksom; 2) analiza obima potro&scaron;nje i strukture antidijabetičnih lekova u op&scaron;tini Foča i poređenje sa savremenim farmakoterapijskim smernicama; 3) određivanje procenta pokrivenosti antidijabetičnom terapijom pacijenata sa DM tip 2 tokom jedne godine u op&scaron;tini Foča; 4) određivanje adherencije pacijenata sa DM tipa 2 prema antidijabetičnoj terapiji metodom brojanja tableta/doza insulina i putem validiranog upitnika; 5) određivanje kvaliteta života povezanog sa zdravljem pacijenata sa DM tipa 2 u op&scaron;tini Foča primenom validiranog upitnika SF-36v2; 6) određivanje prediktora neadherenije kod primene obe metode merenja adherencije u odnosu na karakteristike i kvalitet života pacijenata sa DM tip 2 u op&scaron;tini Foča. Ispitivanje se sastojalo iz dva dela. U prvom delu sprovedeno je retrospektivno farmakoepidemiolo&scaron;ko praćenje upotrebe antidijabetičnih lekova kao i određivanje strukture ovih lekova na teritoriji Republike Srpske u periodu od 01.01.2013. do 31.12.2013.godine i izvr&scaron;eno je poređenje sa upotrebom i strukturom propisivanja u okolnim zemljama kao i državama sa razvijenom farmakoterapijskom praksom. U drugom delu ispitivanja sprovedeno je farmakoepidemiolo&scaron;ko ispitivanje primene antidijabetičnih lekova na nivou same op&scaron;tine Foča u okviru koje je pored analize obima potro&scaron;nje i strukture antidijabetičnih lekova u istom periodu kao i na teritoriji Republike Srpske i poređenja sa savremenim farmakoterapijskim smernicama, određivan i procenta pokrivenosti antidijabetičnom terapijom mereno redovno&scaron;ću ponovnih popunjavanja recepata od strane lekara op&scaron;te prakse tokom jednogodi&scaron;njeg perioda. Takođe je sprovedeno i ispitivanje adherencije prema antidijabetičnim lekovima primenom dve različite metode merenja kao i kvalitet života pacijenata sa DM tip 2 između 01.01.2015. i 31.12.2015.godine. Ukupna upotreba antidijabetika za lečenje dijabetesa tip 1 i tip 2 na teritoriji Republike Srpske iznosila je 38,29 DDD/1000st/dan. Upotreba insulina i analoga iznosila je 11,28 DDD/1000st/dan. Ukupna upotreba oralnih lekova koji snižavaju glukozu i krvi, isključujući insuline iznosila je 27,01 DDD/1000st/dan, a metformin je najče&scaron;će kori&scaron;ćeni predstavnik. Sličan obim i struktura upotrebe antidijabetičnih lekova utvrđena je i u op&scaron;tini Foča. Procenat pokrivenosti antidijabetičnom terapijom pacijenata sa DM tip 2 tokom jedne godine u op&scaron;tini Foča iznosio je vi&scaron;e od 94,91%. Adherencija određivana metodom brojanja tableta/doza insulina iznosila je 52,3%, a merena primenom validiranog upitnikom iznosila je svega 44,9%. Statistički značajni prediktori neadherencije određivane primenom metode brojanja tableta/doza insulina su doplata cena leka kao i niži skor dimenzije mentalnog zdravlja kada je u pitanju kvalitet života. Prediktori neadherencije merene primenom validiranog upitnikom bili su mu&scaron;ki pol, kao i niži skor dimenzije mentalnog kao i fizičkog zdravlja kada je u pitanju kvalitet života. Na osnovu ovih saznanja, intervencije za pobolj&scaron;anje adherencije pacijenata bi bile usmerene na edukaciju pacijenata mu&scaron;kog pola, zatim na smanjivanje izdataka pacijenata za lekove, &scaron;to će doprineti i boljem kvalitetu života ovih pacijenata.</p> / <p>Although diabetes mellitus (DM) type 2 is a chronic disease whose rate has increased significantly in recent decades, data on the patient&#39;s attitudes towards the medicine and the treatment of diabetes mellitus are rare and relate to individual aspects of the therapy. The main stumbling block in the treatment of diabetes is not taking prescribed drugs regularly, which makes it difficult to maintain normal glycoregulation and contribute to the development of severe complications that significantly affect the quality of life of patients with DM. The disposition of accurate data on the use of antidiabeticdrugs, as well as the insight into the real state of the patient&#39;s relationship with the medication in the treatment of DM type 2, enables the improvement of pharmacotherapeutic practice and the creation of an intervention to improve patient adherence.<br />The objectives of this research were:<br />1) analysis of the volume of consumption and structure of anti-diabetic medicines on the territory of the Republic of Srpska and their comparison with the use and structure of prescribing in the surrounding countries as well as countries with developed pharmacotherapeutic practice;<br />2) analysis of the volume of consumption and structure of antidiabetic drugs in the municipality of Foča and comparison with modern pharmacotherapeutic guidelines;<br />3) determining the percentage of coverage with antidiabetic therapy of patients with DM type 2 during one year in the municipality of Foča;<br />4) determining the adherence of patients with DM type 2 in antidiabetic therapy by the method of pill counts /volume of insulin and by validated questionnaire;<br />5) determining the quality of life associated with the health of patients with DM type 2 in the municipality of Foča using the validated questionnaire SF-36v2;<br />6) determination of the predictor of nonadherence in the application of both methods of adherence measurement in relation to the characteristics and quality of life of patients with DM type 2 in the municipality of Foča.<br />The investigation consisted of two parts.<br />In the first part, a retrospective pharmacoepidemiological monitoring of the use of antidiabetic drugs was carried out, as well as determining the structure of these drugs in the territory of the Republic of Srpska in the period from January, 1st 2013 until December, 31st 2013, and a comparison was made with the use and prescription structure in neighboring countries as well as countries with developed pharmacotherapeutic practices. In the second part of the study, a pharmacoepidemiological study was carried out on the use of antidiabetic drugs at the level of the municipality of Foča itself, in which, besides analyzing the volume of consumption and structure of anti-diabetic drugs in the same period as in the territory of the Republic of Srpska and comparison with modern pharmacotherapeutic guidelines, the percentage of coverage by antidiabetic therapy was measured by the regularity of the prescription prescribed by the general practitioner over a one-year period. Medication adherence to antidiabetic drugs was also carried out using two different methods of measurement as well as the quality of life of patients with DM type 2 between January, 1st 2015 and December, 31st 2015. The total use of antidiabetic for the treatment of type 1 diabetes and type 2 in the territory of the Republic of Srpska was 38.29 DDD / 1000st / day. The use of insulin and analogs was 11.28 DDD / 1000st / day. The total use of blood glucose lowering drugs , excluding insulins, was 27.01 DDD / 1000st / day, and metformin is the most commonly used representative. A similar volume and structure of the use of anti-diabetic drugs was also determined in the municipality of Foča. The percentage of coverage of antidiabetic therapy of patients with DM type 2 during one year in the municipality of Foca amounted to more than 94.91%. Adherence determined by the pill counts and the volume of insulin method was 52.3%, and measured by applying the validated questionnaire was only 44.9%. Statistically significant predictors of nonadherence determined by the method of pill counts/volume of insulin are copayment, a fix fee for prescription made by patients as well as the lower score of the mental health dimension when it comes to quality of life. The non-adherence predictors measured using the validated questionnaire were the male sex, as well as a lower score of the mental dimension as well as physical health when it comes to quality of life. Based on these findings, interventions to improve patient adherence would focus on health education of male patients, and policy changes regarding availability of antidiabetic medication through copayment reductions , which will contribute to a better quality of life for these patients.</p>

<p>Zastupljenost deficita vitamina D3 je mnogo veći kod bolesnika sa dijabetesnom bolesti tipa 2 nego u populaciji zdravih osoba. Bolesnici sa DM tipa 2 i deficitom vitamina D3 imaju veći rizik za razvoj dijabetesne nefropatije. Eksperimenti na životinjama i neka klinička istraživanja ukazuju da bi primena nižih doza vitamina D3 mogla imati renoproktektivno delovanje. Cilj istraživanja je bio da se utvrdi zastupljenost deficita vitamina D3 u populaciji bolesnika sa dijabetesnom nefropatijom koja je definisana proteinurijom ˃0,150 g/du. Drugi cilj je bio da se utvrdi da li primena holekaciferola u dozi koja predstavlja razliku između utvrđenog i optimalnog nivoa vitamina D3 dovodi do statistički značajnog smanjenja proteinurije. Bolesnici sa dijabetesom tipa 2 i proteinurijom ˃0,150 g/du su uključivani u skrining na nivo vitamina D3 (25(OH)D) nakon čega su svrstavani u grupe sa deficitom i normalnim nivoom vitamina D3. Granična vrednost za utvrđivanje deficita vitamina D3 je odreĎivana na osnovu tabele koja defini&scaron;e ove vrednosti za svaki mesec tokom godine, posebno za mu&scaron;karce i žene. Bolesnici sa deficitom vitamina D3 su podeljeni u 2 grupe od po 45 ispitanika. Studijska grupa je primala holekaciferol u dozi koja je izračunata na osnovu razlike između izmerene vrednosti i određenog optimalnog nivoa vitamina D3 od 90-100 nmol/L. Kontrolna grupa bolesnika je uzimala svoju uobičajenu terapiju. Istraživanje je trajalo 24 nedelje tokom koje su na drugi mesec praćeni parametri bubrežne funkcije, parametri inflamacije i ko&scaron;tanog metabolizma. Na početku i kraju istraživanja su odreĎeni nivo vitamina D3 u studijskoj grupi, dok su u obe grupe određivani vrednost HbA1c i lipidni profil. Analizom dobijenih podataka je utvrđeno da je zastupljenost deficita vitamina D3 kod bolesnika sa dijabetesnom nefropatijom, uzimajući u obzir sezonske varijacije u nivou ovog vitamina, bila veća od vrednosti od 30-50% koje su postavljene u radnoj hipotezi. Učestalost bolesnika sa nedostakom vitamina D3 je u ispitivanom uzorku je bila 82,56% , dok je normalne vrednosti vitamina D3 imalo 17,43% ispitanika, od toga je bilo 10 (52,63%) mu&scaron;karaca i 9 (47,36%) žena. Sniženje vrednosti vitamina D3 u odnosu na donje granične vrednosti je bilo izraženije u letnjem periodu i bilo je statistički značajno kod svih ispitanika zajedno, potom u studijskoj grupi, dok je utvrđeno i u kontrolnoj grupi ali je u njoj bilo bez statisičke značajnosti. Utvrđen je porast HbA1c koji je bio veći u kontrolnoj grupi ispitanika. Suplementacija vitaminom D3 je imala povoljan efekat na lipidni profil. Registrovan je porast vrednosti ukupnog holesterola koji je bio izraženiji u kontrolnoj grupi, pad vrednosti triglicerida u grupi bolesnika koji su uzimali vitamin D3 i njihov porast u kontrolnoj grupi ispitanika. U studijskoj grupi je registrovan porast vrednosti HDL-holesterola koji je bio na granici statističke značajnosti dok je istovremeno nađeno njegovo smanjenje u kontrolnoj grupi. Vrednost LDL-holesterola je ostala bez promene pod delovanjem vitamina D3, dok je u kontrolnoj grupi do&scaron;lo do njegovog porasta. Utvrđeno je snižavanje vrednosti sedimentije, CRP-a i fibrinogena koje je bilo bez statističke značajnosti. Bezbednosni profil vrednosti kalcijuma u serumu i urinu tokom dugotrajnije primene je dobar. Primenom vitamina D3 je do&scaron;lo do signifikatnog smanjenja proteinurije u grupi bolesnika koji su primali holekaciferol čime je ujedno i potvrđena radna hipoteza.</p> / <p>The prevalence of vitamin D3 deficiency is much higher in patients with type 2 diabetes than in the healthy population. Patients with type 2 DM and vitamin D3 deficiency are at increased risk for developing diabetic nephropathy. Animal experiments and some clinical studies suggest that administration of lower doses of vitamin D3 could have renoprotective effect. The aim of the study was to determine the prevalence of vitamin D3 deficiency in the population of patients with diabetic nephropathy defined by proteinuria ˃0.150 g / du. The second goal was to determine whether the use of cholecaciferol in a dose that represents the difference between the established and optimal levels of vitamin D3 leads to a statistically significant reduction in proteinuria. Patients with type 2 diabetes and proteinuria ˃0.150 g / du were screened for vitamin D3 (25 (OH) D) levels and then classified as deficient and normal vitamin D3. The limit value for determining vitamin D3 deficiency was set on the basis of a table defining these values for each month during the year, separately for men and women. Patients with vitamin D3 deficiency were divided into 2 groups of 45 subjects each. The study group received cholecaciferol at a dose calculated on the basis of the difference between the measured value and the set optimal vitamin D 3 level of 90-100 nmol/L. The control group of patients was taking their usual therapy. The study lasted 24 weeks during which the parameters of renal function, parameters of inflammation and bone metabolism were monitored every second month. At the beginning and end of the study, the levels of vitamin D3 in the study group were determined, while in both groups HbA1c and lipid profile were determined. The analysis of the obtained data showed that the prevalence of vitamin D3 deficiency in patients with diabetic nephropathy, taking into account seasonal variations in the level of this vitamin, was higher than the values of 30-50%, which were set in the working hypothesis. The frequency of patients with vitamin D3 deficiency in the study sample was 82.56%, while the normal values of vitamin D3 were in 17.43% of the subjects, of which 10 (52.63%) were men and 9 (47.36%) woman. The decrease in vitamin D3 compared to the lower limit values was more pronounced in the summer and was statistically significant in all subjects together, as well in the study group, while it was also found in the control group but was not statistically significant. An increase in HbA1c was found to be higher in the control group. Vitamin D3 supplementation had a beneficial effect on the lipid profile. An increase in the total cholesterol level that was more pronounced in the control group, a decrease in triglyceride values in the group of patients taking vitamin D3 and its increase in the control group of subjects were registered. An increase in HDL-cholesterol was reported in the study group, which was at the limit of statistical significance, while at the same time a decrease was found in the control group. LDL-cholesterol levels remained unchanged under the influence of vitamin D3, while in the control group it increased. The decrease in sedimentation, CRP and fibrinogen values was found to be of no statistical significance. The safety profile of serum and urine calcium during long-term administration is good. The use of vitamin D3 resulted in a significant decrease in proteinuria in the group of patients receiving cholecaciferol, which also confirmed the working hypothesis.</p>